Parkinson DiseaseNCT04651478
Mental Representation Techniques for the Treatment of Parkinson´s Disease-related Pain
A study testing Action Observation+Motor Imagery through BCI and Action Observation through non-related with movement illustrations in people with Parkinson Disease and Pain, run by Universidad Francisco de Vitoria at 1 site in Spain.
Trial summary
Pain is an under-reported but prevalent symptom in Parkinson´s Disease (PD), impacting patients' quality of life. Both pain and PD conditions cause cortical excitability reduction, but mental representations techniques are thought to be able to counteract it, resulting also effective in chronic pain conditions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson Disease, Pain
- What is being tested?
- Action Observation+Motor Imagery through BCI and Action Observation through non-related with movement illustrations
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 1 siteSpain
- Study dates
- 3 May 2021to Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Neuroimaging study without previous pathologies.
- Score > 5 in transfers (bed to chair and back) item in Barthel Index.
- Score = or > 24 in Mini-Mental State Examination.
- Able to provide informed consent to participate in the study.
Who cannot join
- History of neurologic disease different from PD.
- Presence of non-related to PD pain.
- Dermatologic problems, wounds, or ulcers in the electrode's application area.
- Significative difficulties in language.
- History of alcohol or drugs abuse.
- Non-controlled medical problems.
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Beata María Ana
Madrid, 28007
Juan Pablo Romero Muñoz, MD. PhD., +34917091400 ext. 1688, p.romero.prof@ufv.es
Yeray Gonzalez Zamorano, PT Msc.
About this study
Official title: Mental Representation Techniques Targeting Pain in Parkinson´s Disease Patients: A Randomized Controlled Trial
Pain is an under-reported but prevalent symptom in Parkinson´s Disease (PD), impacting patients' quality of life. Both pain and PD conditions cause cortical excitability reduction, but mental representations techniques are thought to be able to counteract it, resulting also effective in chronic pain conditions. The investigators of the present project aim to evaluate the efficacy of a novel mental representation protocol in the management of pain in PD patients during the ON state. The investigators hypothesize that Action Observation (AO) and Motor Imagery (MI) training through a Brain-Computer Interface (BCI) using Virtual Reality (AO+MI-BCI) can improve clinical pain and its central processing features.
Read the detailed description
Parkinson´s Disease (PD) affects between 4.1 and 4.6 million people in the world. The diagnosis of PD is currently clinical and based on its motor manifestations (bradykinesia, rest tremor, and rigidity). However, non-motor symptoms such as pain, fatigue, and neuropsychiatric manifestations are present in more than 70% of subjects. Pain affects about 85% of patients but is paradoxically under-reported and consequently under-treated in PD patients with a great impact on their quality of life. Levodopa, which is the election treatment in PD, has shown controversial results regarding pain sensitivity and has been shown ineffective for enhancing the endogenous pain modulation system. Furthermore, there is a lack of management protocols and nonpharmacologic treatments for pain in PD. Several syndromes are hypothesized to be involved in PD pain generation. Generally, PD patients suffer from alterations in peripheral transmission, sensitive-discriminative processing, pain perception, and pain interpretation in multiple levels, due to neurodegenerative changes in dopaminergic pathways and non-dopaminergic pain-related structures. Therefore, central mechanisms are proposed to be crucial for the development and establishment of pain in PD patients. Regarding pain processing features, PD patients have reduced pain thresholds, an augmented Temporal Summation (TS) after repetitive nociceptive stimulus, and the impairment of their Conditioned Pain Modulation (CPM) is correlated with greater severity and premature onset of the disease. Cortical excitability reduction is common in patients with pain. Therefore, diverse therapies are being developed to counteract this cortical excitability reduction and obtaining, consequently, effective pain relief. In consonance with these findings, in PD condition, especially in off state, there is also evidence of cortical excitability decrease but, to the best of investigators´ knowledge, there are no studies targeting cortical excitability to treat pain in PD. Thus, the present study proposes mental representation techniques for the treatment of PD-related pain. The mental representation techniques included in the protocol will be Action Observation (AO) and Motor Imagery (MI). The combination of AO and MI has shown to synergically increase cortical excitability, influencing the activation of cortical areas such as M1 and DLPFC. Specifically in PD, AO and MI have also demonstrated to produce corticomotor facilitation. In addition, mental representation training can produce neurophysiological activity similar to actual exercise training, which has shown to decrease the intensity and severity of pain in PD patients. The main aim of this study is to conduct an independent parallel randomized controlled trials based on AO+MI-BCI targeting changes in 1. validated general and specific PD related pain scales and 2. psychophysical measurements of pain modulation mechanisms. The investigators´ main hypothesis is that AO+MI-BCI will be superior to their respective control placebo intervention.
- Conditions
- Parkinson Disease, Pain
- Being tested
- Action Observation+Motor Imagery through BCI, Action Observation through non-related with movement illustrations
- Keywords
- Parkinson Disease, Pain, Action Observation, Motor Imagery, Virtual Reality
- Medical subject headings
- Parkinson Disease, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Action Observation+Motor Imagery through BCIBehavioural
Patients will undergo the treatment through the NeuRow platform. NeuRow is a gamified Brain-Computer Interface training paradigm in Virtual Reality (or neurogame) that allows patients to perform the same actions as they would do in real-life by imaging the movement. In NeuRow, patients will see a boat and two high fidelity virtual arms gripping two oars in the first-person view. Patients will have to imagine the movement of each corresponding hand to rotate each oar and progress, observing the movement imagined on screen. The goal of the task is to collect as many flags as possible in a fixed amount of time. In order to improve adherence, the number of flags collected will be recorded in each session. It will be able to adapt the boat speed, turn speed, and cut-off angle, to help patients not to deviate in excess from the target. The treatment itself will be performed for 20 minutes each session, divided into 4 series of 5 minutes to prevent fatigue.
Action Observation through non-related with movement illustrationsBehavioural
The same configuration will be applied to simulate a BCI task, but playing a video about graphic illustrations, people's faces, and landscapes, never related to human movement. They will address interesting and changing topics to avoid patient's boredom. The control session will last 20 minutes, also divided into 4 series of 5 minutes and the therapist will give the instructions of observing and relax.
| Study group | Role | What they receive |
|---|---|---|
| Action Observation+Motor Imagery through BCI | Experimental | Action Observation+Motor Imagery through a Brain-Computer Interface training paradigm in Virtual Reality using the "NeuRow" platform during 10 sessions of 20 minutes, divided in 4 series of 5 minutes. Receives: Behavioral: Action Observation+Motor Imagery through BCI |
| Action Observation through non-related with movement illustrations | Placebo comparator | Control Action Observation protocol of non-related with movement illustrations during 10 sessions of 20 minutes, divided in 4 series of 5 minutes. Receives: Behavioral: Action Observation through non-related with movement illustrations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in King´s Parkinson´s Disease Pain Scale score
Parkinson´s Disease specific scale that evaluates the localization, frequency, and intensity of pain. It has 14 items distributed in 7 domains: 1. Musculoskeletal Pain; 2. Chronic Pain; 3. Fluctuation-related Pain; 4. Nocturnal Pain; 5. Oro-facial Pain; 6. Discoloration, Oedema/Swelling Pain; 7. Radicular Pain. Each item is scored by severity (0, none to 3, very severe) multiplied by frequency (0, never to 4, all the time) resulting in a subscore of 0 to 12, the sum of which gives the total score with a theoretical range from 0 to 168, with higher scores indicating more severity and frequency of pain.
Measured: From Baseline at 2 weeks
Change in King´s Parkinson´s Disease Pain Scale score
Parkinson´s Disease specific scale that evaluates the localization, frequency, and intensity of pain. It has 14 items distributed in 7 domains: 1. Musculoskeletal Pain; 2. Chronic Pain; 3. Fluctuation-related Pain; 4. Nocturnal Pain; 5. Oro-facial Pain; 6. Discoloration, Oedema/Swelling Pain; 7. Radicular Pain. Each item is scored by severity (0, none to 3, very severe) multiplied by frequency (0, never to 4, all the time) resulting in a subscore of 0 to 12, the sum of which gives the total score with a theoretical range from 0 to 168, with higher scores indicating more severity and frequency of pain.
Measured: From Baseline at 1 month
Change in Brief Pain Inventory score
It contains 15 items, including 2 multi-item scales to measure the intensity of pain and its impact on the function and welfare of patients. It also presents open questions to assess the localization of pain and the treatment used for its management, just as its effectiveness. Scores oscillate from 0 to 110, with higher scores indicating more pain and more impact on function and welfare of patients.
Measured: From Baseline at 2 weeks
Change in Brief Pain Inventory score
It contains 15 items, including 2 multi-item scales to measure the intensity of pain and its impact on the function and welfare of patients. It also presents open questions to assess the localization of pain and the treatment used for its management, just as its effectiveness. Scores oscillate from 0 to 110, with higher scores indicating more pain and more impact on function and welfare of patients.
Measured: From Baseline at 1 month
Change in Conditioned Pain Modulation
Assesses the descending pain modulatory system. The Pain Pressure Threshold will be assessed in the middle of the distal phalanx of the thumb with ta handheld algometer, corresponding to the first test stimulus. Afterward, the patient will immerse the contrary hand up to the wrist into stirred ice-cold water (0-4º) maintaining it for 3 minutes, corresponding to the conditioning stimulus. If the pain is unbearable before the 3 minutes, the patient will be able to remove his/her hand. Immediately after removing the hand, a second Pain Pressure Threshold measure will be performed in the same place as the first one, corresponding to the second test stimulus. After 1-minute rest, a third Pain Pressure Threshold will be measured to assess the Conditioned Pain Modulation residual functioning.
Measured: From Baseline at 2 weeks
Change in Conditioned Pain Modulation
Assesses the descending pain modulatory system. The Pain Pressure Threshold will be assessed in the middle of the distal phalanx of the thumb with ta handheld algometer, corresponding to the first test stimulus. Afterward, the patient will immerse the contrary hand up to the wrist into stirred ice-cold water (0-4º) maintaining it for 3 minutes, corresponding to the conditioning stimulus. If the pain is unbearable before the 3 minutes, the patient will be able to remove his/her hand. Immediately after removing the hand, a second Pain Pressure Threshold measure will be performed in the same place as the first one, corresponding to the second test stimulus. After 1-minute rest, a third Pain Pressure Threshold will be measured to assess the Conditioned Pain Modulation residual functioning.
Measured: From Baseline at 1 month
Change in Temporal Summation
Represents excitatory modulation processes. It will be generated through the application of 10 pulses of the handheld pressure algometer over the middle of the distal phalanx of the thumb with the intensity of the Pain Pressure Threshold, previously calculated. In each pulse, pressure intensity will be increasing at a rate of 2 kg/s over the previously determined Pain Pressure Threshold intensity, leaving an interstimulus interval of one second according to the optimal method reported for inducing Temporal Summation with pressure pain. Before the first pressure pulse, subjects were taught to use a verbal numeric pain rating scale to rate the pain intensity of the first, fifth, and 10th pressure pulses. The verbal numeric pain rating scale ranged from 0 ("no pain") to 10 ("the worst possible pain").
Measured: From Baseline at 2 weeks
Change in Temporal Summation
Represents excitatory modulation processes. It will be generated through the application of 10 pulses of the handheld pressure algometer over the middle of the distal phalanx of the thumb with the intensity of the Pain Pressure Threshold, previously calculated. In each pulse, pressure intensity will be increasing at a rate of 2 kg/s over the previously determined Pain Pressure Threshold intensity, leaving an interstimulus interval of one second according to the optimal method reported for inducing Temporal Summation with pressure pain. Before the first pressure pulse, subjects were taught to use a verbal numeric pain rating scale to rate the pain intensity of the first, fifth, and 10th pressure pulses. The verbal numeric pain rating scale ranged from 0 ("no pain") to 10 ("the worst possible pain").
Measured: From Baseline at 1 month
Changes in Pain Pressure Threshold
Two Pain Pressure Thresholds will be measured by a handheld algometer, one over the most painful area (peripheric hyperalgesia) and the other one over the middle of the distal phalanx of the thumb (central hyperalgesia). The Pain Pressure Threshold will be applied with the algometer perpendicular to the skin increasing at a rate of 1 kg/s until the first sensation of pain. 3 measures with 30-seconds rest between them will be performed, taking the average as Pain Pressure Threshold.
Measured: From Baseline at 2 weeks
Changes in Pain Pressure Threshold
Two Pain Pressure Thresholds will be measured by a handheld algometer, one over the most painful area (peripheric hyperalgesia) and the other one over the middle of the distal phalanx of the thumb (central hyperalgesia). The Pain Pressure Threshold will be applied with the algometer perpendicular to the skin increasing at a rate of 1 kg/s until the first sensation of pain. 3 measures with 30-seconds rest between them will be performed, taking the average as Pain Pressure Threshold.
Measured: From Baseline at 1 month
Secondary outcomes (21)
Beck Depression Inventory
Measures depressive symptoms. Scores range from 0 to 63 leading to 6 groups: 0-10, normal; 11-16, mild mood disturbance; 17-20, borderline clinical depression; 21-30, moderate depression; 31-40, severe depression; and over 40, extreme depression.
Measured: Baseline
Beck Depression Inventory
Measures depressive symptoms. Scores range from 0 to 63 leading to 6 groups: 0-10, normal; 11-16, mild mood disturbance; 17-20, borderline clinical depression; 21-30, moderate depression; 31-40, severe depression; and over 40, extreme depression.
Measured: At 2 weeks from Baseline
Beck Depression Inventory
Measures depressive symptoms. Scores range from 0 to 63 leading to 6 groups: 0-10, normal; 11-16, mild mood disturbance; 17-20, borderline clinical depression; 21-30, moderate depression; 31-40, severe depression; and over 40, extreme depression.
Measured: At 1 month from Baseline
State-Trait Anxiety Inventory
Measures anxious states and anxious traits. It has 20 items for assessing trait anxiety and 20 for state anxiety. All items are rated on a 4-point scale (e.g., from "Almost Never" to "Almost Always"). Higher scores indicate greater anxiety.
Measured: Baseline
State-Trait Anxiety Inventory
Measures anxious states and anxious traits. It has 20 items for assessing trait anxiety and 20 for state anxiety. All items are rated on a 4-point scale (e.g., from "Almost Never" to "Almost Always"). Higher scores indicate greater anxiety.
Measured: At 2 weeks from Baseline
State-Trait Anxiety Inventory
Measures anxious states and anxious traits. It has 20 items for assessing trait anxiety and 20 for state anxiety. All items are rated on a 4-point scale (e.g., from "Almost Never" to "Almost Always"). Higher scores indicate greater anxiety.
Measured: At 1 month from Baseline
Tampa Scale of Kinesiophobia
Measures fear of movement-related pain. Its scores range from 11-44 points with higher scores indicating greater fear of pain, movement, and injury.
Measured: Baseline
Tampa Scale of Kinesiophobia
Measures fear of movement-related pain. Its scores range from 11-44 points with higher scores indicating greater fear of pain, movement, and injury.
Measured: At 2 weeks from Baseline
Tampa Scale of Kinesiophobia
Measures fear of movement-related pain. Its scores range from 11-44 points with higher scores indicating greater fear of pain, movement, and injury.
Measured: At 1 month from Baseline
Pain Catastrophizing Scale
Measures catastrophizing thinking. Its total score range from 0-52, along with three subscale scores assessing rumination, magnification and helplessness, with higher scores indicating higher level of catastrophizing.
Measured: Baseline
Pain Catastrophizing Scale
Measures catastrophizing thinking. Its total score range from 0-52, along with three subscale scores assessing rumination, magnification and helplessness, with higher scores indicating higher level of catastrophizing.
Measured: At 2 weeks from Baseline
Pain Catastrophizing Scale
Measures catastrophizing thinking. Its total score range from 0-52, along with three subscale scores assessing rumination, magnification and helplessness, with higher scores indicating higher level of catastrophizing.
Measured: At 1 month from Baseline
Unified Parkinson´s Disease Rating Scale
Measures disability in Parkinson´s Disease patients. The scale itself has four components: Part I, Mentation, Behavior and Mood; Part II, Activities of Daily Living; Part III, Motor aspects; Part IV, Associated Complications. Scores range from 0 to 159 with higher scores indicating more severity.
Measured: Baseline
Unified Parkinson´s Disease Rating Scale
Measures disability in Parkinson´s Disease patients. The scale itself has four components: Part I, Mentation, Behavior and Mood; Part II, Activities of Daily Living; Part III, Motor aspects; Part IV, Associated Complications. Scores range from 0 to 159 with higher scores indicating more severity.
Measured: At 2 weeks from Baseline
Unified Parkinson´s Disease Rating Scale
Measures disability in Parkinson´s Disease patients. The scale itself has four components: Part I, Mentation, Behavior and Mood; Part II, Activities of Daily Living; Part III, Motor aspects; Part IV, Associated Complications. Scores range from 0 to 159 with higher scores indicating more severity.
Measured: At 1 month from Baseline
Reaction Times
Performed through 2 related subtasks. Finger Taping task, where the participants will be instructed to press the space bar on the keyboard as fast as possible and repeatedly with the index finger, to measure motor function. And Simple Reaction Time task, where participants will be instructed to press the left mouse button as fast as possible when the stimulus "+" appears in the center of the screen at a size of 2 cm x 2 cm, to measure simple perception and sustained alertness.
Measured: Baseline
Reaction Times
Performed through 2 related subtasks. Finger Taping task, where the participants will be instructed to press the space bar on the keyboard as fast as possible and repeatedly with the index finger, to measure motor function. And Simple Reaction Time task, where participants will be instructed to press the left mouse button as fast as possible when the stimulus "+" appears in the center of the screen at a size of 2 cm x 2 cm, to measure simple perception and sustained alertness.
Measured: At 2 weeks from Baseline
Reaction Times
Performed through 2 related subtasks. Finger Taping task, where the participants will be instructed to press the space bar on the keyboard as fast as possible and repeatedly with the index finger, to measure motor function. And Simple Reaction Time task, where participants will be instructed to press the left mouse button as fast as possible when the stimulus "+" appears in the center of the screen at a size of 2 cm x 2 cm, to measure simple perception and sustained alertness.
Measured: At 1 month from Baseline
Transcranial Magnetic Stimulation
Action Motor Threshold in millivolts
Measured: Baseline
Transcranial Magnetic Stimulation
Action Motor Threshold in millivolts
Measured: At 2 weeks from Baseline
Transcranial Magnetic Stimulation
Action Motor Threshold in millivolts
Measured: At 1 month from Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2020
- Study start3 May 2021 (estimated)
- Primary completionOct 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study will be a double-blinded experimental longitudinal prospective randomized controlled trial with a parallel design. The randomization will be realized through randomization software. All the participants who fulfill the inclusion criteria and have none of the exclusion ones will be randomly allocated into two groups: AO+MI through a Brain-Computer Interface (BCI) training paradigm in Virtual Reality (VR) (AO+MI-BCI) or AO of non-related with movement illustrations (AO-control). Allocation concealment will be ensured by the inclusion of the assigned group in closed opaque envelopes that will be opened at the time of the intervention.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universidad Francisco de Vitoria
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Beata María Ana, Universidad Rey Juan Carlos
- Responsible party
- Sponsor
- Investigators
- Juan Pablo Romero Muñoz, MD PhD, Principal investigator, Universidad Francisco de Vitoria, Facultad de Ciencias ExperimentalesJosue Fernández Carnero, PT PhD, Principal investigator, Universidad Rey Juan Carlos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04651478
- Sponsor's protocol ID
- PainPD-Imagine
- Status last verified
- Mar 2021
- First submitted
- 19 Nov 2020
- Last updated
- 23 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual anonymized participant data will be available to other researchers under request.
Publications
Kalia LV, Lang AE. Parkinson's disease. Lancet. 2015 Aug 29;386(9996):896-912. doi: 10.1016/S0140-6736(14)61393-3. Epub 2015 Apr 19.
PubMed 25904081Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, Chaudhuri KR; NMSS Validation Group. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson's disease. Mov Disord. 2011 Feb 15;26(3):399-406. doi: 10.1002/mds.23462. Epub 2011 Jan 24.
PubMed 21264941Antonini A, Tinazzi M, Abbruzzese G, Berardelli A, Chaudhuri KR, Defazio G, Ferreira J, Martinez-Martin P, Trenkwalder C, Rascol O. Pain in Parkinson's disease: facts and uncertainties. Eur J Neurol. 2018 Jul;25(7):917-e69. doi: 10.1111/ene.13624. Epub 2018 Apr 18.
PubMed 29520899Wright DJ, Williams J, Holmes PS. Combined action observation and imagery facilitates corticospinal excitability. Front Hum Neurosci. 2014 Nov 27;8:951. doi: 10.3389/fnhum.2014.00951. eCollection 2014.
PubMed 25505880Vourvopoulos A, Ferreira A, Bermúdez i Badia S. NeuRow: An Immersive VR Environment for Motor-Imagery Training with the Use of Brain-Computer Interfaces and Vibrotactile Feedback. 2016.
Morales Tejera D, Fernandez-Carnero J, Suso-Marti L, Cano-de-la-Cuerda R, Lerin-Calvo A, Remon-Ramiro L, La Touche R. Comparative study of observed actions, motor imagery and control therapeutic exercise on the conditioned pain modulation in the cervical spine: a randomized controlled trial. Somatosens Mot Res. 2020 Sep;37(3):138-148. doi: 10.1080/08990220.2020.1756244. Epub 2020 Apr 27.
PubMed 32340585Vourvopoulos A, Jorge C, Abreu R, Figueiredo P, Fernandes JC, Bermudez I Badia S. Efficacy and Brain Imaging Correlates of an Immersive Motor Imagery BCI-Driven VR System for Upper Limb Motor Rehabilitation: A Clinical Case Report. Front Hum Neurosci. 2019 Jul 11;13:244. doi: 10.3389/fnhum.2019.00244. eCollection 2019.
PubMed 31354460Chaudhuri KR, Rizos A, Trenkwalder C, Rascol O, Pal S, Martino D, Carroll C, Paviour D, Falup-Pecurariu C, Kessel B, Silverdale M, Todorova A, Sauerbier A, Odin P, Antonini A, Martinez-Martin P; EUROPAR and the IPMDS Non Motor PD Study Group. King's Parkinson's disease pain scale, the first scale for pain in PD: An international validation. Mov Disord. 2015 Oct;30(12):1623-31. doi: 10.1002/mds.26270. Epub 2015 Jun 11.
PubMed 26096067Perez-Lloret S, Ciampi de Andrade D, Lyons KE, Rodriguez-Blazquez C, Chaudhuri KR, Deuschl G, Cruccu G, Sampaio C, Goetz CG, Schrag A, Martinez-Martin P, Stebbins G; Members of the MDS Committee on Rating Scales Development. Rating Scales for Pain in Parkinson's Disease: Critique and Recommendations. Mov Disord Clin Pract. 2016 Jun 24;3(6):527-537. doi: 10.1002/mdc3.12384. eCollection 2016 Nov-Dec.
PubMed 30363588Imai Y, Petersen KK, Morch CD, Arendt Nielsen L. Comparing test-retest reliability and magnitude of conditioned pain modulation using different combinations of test and conditioning stimuli. Somatosens Mot Res. 2016 Sep-Dec;33(3-4):169-177. doi: 10.1080/08990220.2016.1229178. Epub 2016 Sep 20.
PubMed 27650216Santos-Garcia D, Oreiro M, Perez P, Fanjul G, Paz Gonzalez JM, Feal Painceiras MJ, Cores Bartolome C, Valdes Aymerich L, Garcia Sancho C, Castellanos Rodrigo MDM. Impact of Coronavirus Disease 2019 Pandemic on Parkinson's Disease: A Cross-Sectional Survey of 568 Spanish Patients. Mov Disord. 2020 Oct;35(10):1712-1716. doi: 10.1002/mds.28261. Epub 2020 Sep 22.
PubMed 32776601
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mental Representation Techniques Targeting Pain in Parkinson´s Disease Patients: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04651478
- Acronym / sponsor ID
- PainPD-Imagine
- Conditions
- Parkinson Disease, Pain
- Keywords
- Parkinson Disease, Pain, Action Observation, Motor Imagery, Virtual Reality
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Universidad Francisco de VitoriaUniversity, hospital or other
- Collaborators
- Hospital Beata María Ana, Universidad Rey Juan Carlos
- Study start
- 3 May 2021 (estimated)
- Primary completion
- Oct 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 3 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pain is an under-reported but prevalent symptom in Parkinson´s Disease (PD), impacting patients' quality of life. Both pain and PD conditions cause cortical excitability reduction, but mental representations techniques are thought to be able to counteract it, resulting also effective in chronic pain conditions. The investigators of the present project aim to evaluate the efficacy of a novel mental representation protocol in the management of pain in PD patients during the ON state. The investigators hypothesize that Action Observation (AO) and Motor Imagery (MI) training through a Brain-Computer Interface (BCI) using Virtual Reality (AO+MI-BCI) can improve clinical pain and its central processing features.
Detailed description
Parkinson´s Disease (PD) affects between 4.1 and 4.6 million people in the world. The diagnosis of PD is currently clinical and based on its motor manifestations (bradykinesia, rest tremor, and rigidity). However, non-motor symptoms such as pain, fatigue, and neuropsychiatric manifestations are present in more than 70% of subjects. Pain affects about 85% of patients but is paradoxically under-reported and consequently under-treated in PD patients with a great impact on their quality of life. Levodopa, which is the election treatment in PD, has shown controversial results regarding pain sensitivity and has been shown ineffective for enhancing the endogenous pain modulation system. Furthermore, there is a lack of management protocols and nonpharmacologic treatments for pain in PD. Several syndromes are hypothesized to be involved in PD pain generation. Generally, PD patients suffer from alterations in peripheral transmission, sensitive-discriminative processing, pain perception, and pain interpretation in multiple levels, due to neurodegenerative changes in dopaminergic pathways and non-dopaminergic pain-related structures. Therefore, central mechanisms are proposed to be crucial for the development and establishment of pain in PD patients. Regarding pain processing features, PD patients have reduced pain thresholds, an augmented Temporal Summation (TS) after repetitive nociceptive stimulus, and the impairment of their Conditioned Pain Modulation (CPM) is correlated with greater severity and premature onset of the disease. Cortical excitability reduction is common in patients with pain. Therefore, diverse therapies are being developed to counteract this cortical excitability reduction and obtaining, consequently, effective pain relief. In consonance with these findings, in PD condition, especially in off state, there is also evidence of cortical excitability decrease but, to the best of investigators´ knowledge, there are no studies targeting cortical excitability to treat pain in PD. Thus, the present study proposes mental representation techniques for the treatment of PD-related pain. The mental representation techniques included in the protocol will be Action Observation (AO) and Motor Imagery (MI). The combination of AO and MI has shown to synergically increase cortical excitability, influencing the activation of cortical areas such as M1 and DLPFC. Specifically in PD, AO and MI have also demonstrated to produce corticomotor facilitation. In addition, mental representation training can produce neurophysiological activity similar to actual exercise training, which has shown to decrease the intensity and severity of pain in PD patients. The main aim of this study is to conduct an independent parallel randomized controlled trials based on AO+MI-BCI targeting changes in 1. validated general and specific PD related pain scales and 2. psychophysical measurements of pain modulation mechanisms. The investigators´ main hypothesis is that AO+MI-BCI will be superior to their respective control placebo intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This study will be a double-blinded experimental longitudinal prospective randomized controlled trial with a parallel design. The randomization will be realized through randomization software. All the participants who fulfill the inclusion criteria and have none of the exclusion ones will be randomly allocated into two groups: AO+MI through a Brain-Computer Interface (BCI) training paradigm in Virtual Reality (VR) (AO+MI-BCI) or AO of non-related with movement illustrations (AO-control). Allocation concealment will be ensured by the inclusion of the assigned group in closed opaque envelopes that will be opened at the time of the intervention.
| Arm | Type | Receives |
|---|---|---|
| Action Observation+Motor Imagery through BCI | Experimental | Behavioral: Action Observation+Motor Imagery through BCIAction Observation+Motor Imagery through a Brain-Computer Interface training paradigm in Virtual Reality using the "NeuRow" platform during 10 sessions of 20 minutes, divided in 4 series of 5 minutes. |
| Action Observation through non-related with movement illustrations | Placebo comparator | Behavioral: Action Observation through non-related with movement illustrationsControl Action Observation protocol of non-related with movement illustrations during 10 sessions of 20 minutes, divided in 4 series of 5 minutes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Neuroimaging study without previous pathologies.
- Score > 5 in transfers (bed to chair and back) item in Barthel Index.
- Score = or > 24 in Mini-Mental State Examination.
- Able to provide informed consent to participate in the study.
Key exclusion criteria (7 listed)
- History of neurologic disease different from PD.
- Presence of non-related to PD pain.
- Dermatologic problems, wounds, or ulcers in the electrode's application area.
- Significative difficulties in language.
- History of alcohol or drugs abuse.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Action Observation+Motor Imagery through BCIPatients will undergo the treatment through the NeuRow platform. NeuRow is a gamified Brain-Computer Interface training paradigm in Virtual Reality (or neurogame) that allows patients to perform the same actions as they would do in real-life by imaging the movement. In NeuRow, patients will see a boat and two high fidelity virtual arms gripping two oars in the first-person view. Patients will have to imagine the movement of each corresponding hand to rotate each oar and progress, observing the movement imagined on screen. The goal of the task is to collect as many flags as possible in a fixed amount of time. In order to improve adherence, the number of flags collected will be recorded in each session. It will be able to adapt the boat speed, turn speed, and cut-off angle, to help patients not to deviate in excess from the target. The treatment itself will be performed for 20 minutes each session, divided into 4 series of 5 minutes to prevent fatigue. | Behavioural | Action Observation+Motor Imagery through BCI |
| Action Observation through non-related with movement illustrationsThe same configuration will be applied to simulate a BCI task, but playing a video about graphic illustrations, people's faces, and landscapes, never related to human movement. They will address interesting and changing topics to avoid patient's boredom. The control session will last 20 minutes, also divided into 4 series of 5 minutes and the therapist will give the instructions of observing and relax. | Behavioural | Action Observation through non-related with movement illustrations |
Primary outcome
Change in King´s Parkinson´s Disease Pain Scale score
Time frame: From Baseline at 2 weeks
Parkinson´s Disease specific scale that evaluates the localization, frequency, and intensity of pain. It has 14 items distributed in 7 domains: 1. Musculoskeletal Pain; 2. Chronic Pain; 3. Fluctuation-related Pain; 4. Nocturnal Pain; 5. Oro-facial Pain; 6. Discoloration, Oedema/Swelling Pain; 7. Radicular Pain. Each item is scored by severity (0, none to 3, very severe) multiplied by frequency (0, never to 4, all the time) resulting in a subscore of 0 to 12, the sum of which gives the total score with a theoretical range from 0 to 168, with higher scores indicating more severity and frequency of pain.
Change in King´s Parkinson´s Disease Pain Scale score
Time frame: From Baseline at 1 month
Parkinson´s Disease specific scale that evaluates the localization, frequency, and intensity of pain. It has 14 items distributed in 7 domains: 1. Musculoskeletal Pain; 2. Chronic Pain; 3. Fluctuation-related Pain; 4. Nocturnal Pain; 5. Oro-facial Pain; 6. Discoloration, Oedema/Swelling Pain; 7. Radicular Pain. Each item is scored by severity (0, none to 3, very severe) multiplied by frequency (0, never to 4, all the time) resulting in a subscore of 0 to 12, the sum of which gives the total score with a theoretical range from 0 to 168, with higher scores indicating more severity and frequency of pain.
Change in Brief Pain Inventory score
Time frame: From Baseline at 2 weeks
It contains 15 items, including 2 multi-item scales to measure the intensity of pain and its impact on the function and welfare of patients. It also presents open questions to assess the localization of pain and the treatment used for its management, just as its effectiveness. Scores oscillate from 0 to 110, with higher scores indicating more pain and more impact on function and welfare of patients.
Change in Brief Pain Inventory score
Time frame: From Baseline at 1 month
It contains 15 items, including 2 multi-item scales to measure the intensity of pain and its impact on the function and welfare of patients. It also presents open questions to assess the localization of pain and the treatment used for its management, just as its effectiveness. Scores oscillate from 0 to 110, with higher scores indicating more pain and more impact on function and welfare of patients.
Change in Conditioned Pain Modulation
Time frame: From Baseline at 2 weeks
Assesses the descending pain modulatory system. The Pain Pressure Threshold will be assessed in the middle of the distal phalanx of the thumb with ta handheld algometer, corresponding to the first test stimulus. Afterward, the patient will immerse the contrary hand up to the wrist into stirred ice-cold water (0-4º) maintaining it for 3 minutes, corresponding to the conditioning stimulus. If the pain is unbearable before the 3 minutes, the patient will be able to remove his/her hand. Immediately after removing the hand, a second Pain Pressure Threshold measure will be performed in the same place as the first one, corresponding to the second test stimulus. After 1-minute rest, a third Pain Pressure Threshold will be measured to assess the Conditioned Pain Modulation residual functioning.
Change in Conditioned Pain Modulation
Time frame: From Baseline at 1 month
Assesses the descending pain modulatory system. The Pain Pressure Threshold will be assessed in the middle of the distal phalanx of the thumb with ta handheld algometer, corresponding to the first test stimulus. Afterward, the patient will immerse the contrary hand up to the wrist into stirred ice-cold water (0-4º) maintaining it for 3 minutes, corresponding to the conditioning stimulus. If the pain is unbearable before the 3 minutes, the patient will be able to remove his/her hand. Immediately after removing the hand, a second Pain Pressure Threshold measure will be performed in the same place as the first one, corresponding to the second test stimulus. After 1-minute rest, a third Pain Pressure Threshold will be measured to assess the Conditioned Pain Modulation residual functioning.
Change in Temporal Summation
Time frame: From Baseline at 2 weeks
Represents excitatory modulation processes. It will be generated through the application of 10 pulses of the handheld pressure algometer over the middle of the distal phalanx of the thumb with the intensity of the Pain Pressure Threshold, previously calculated. In each pulse, pressure intensity will be increasing at a rate of 2 kg/s over the previously determined Pain Pressure Threshold intensity, leaving an interstimulus interval of one second according to the optimal method reported for inducing Temporal Summation with pressure pain. Before the first pressure pulse, subjects were taught to use a verbal numeric pain rating scale to rate the pain intensity of the first, fifth, and 10th pressure pulses. The verbal numeric pain rating scale ranged from 0 ("no pain") to 10 ("the worst possible pain").
Change in Temporal Summation
Time frame: From Baseline at 1 month
Represents excitatory modulation processes. It will be generated through the application of 10 pulses of the handheld pressure algometer over the middle of the distal phalanx of the thumb with the intensity of the Pain Pressure Threshold, previously calculated. In each pulse, pressure intensity will be increasing at a rate of 2 kg/s over the previously determined Pain Pressure Threshold intensity, leaving an interstimulus interval of one second according to the optimal method reported for inducing Temporal Summation with pressure pain. Before the first pressure pulse, subjects were taught to use a verbal numeric pain rating scale to rate the pain intensity of the first, fifth, and 10th pressure pulses. The verbal numeric pain rating scale ranged from 0 ("no pain") to 10 ("the worst possible pain").
Changes in Pain Pressure Threshold
Time frame: From Baseline at 2 weeks
Two Pain Pressure Thresholds will be measured by a handheld algometer, one over the most painful area (peripheric hyperalgesia) and the other one over the middle of the distal phalanx of the thumb (central hyperalgesia). The Pain Pressure Threshold will be applied with the algometer perpendicular to the skin increasing at a rate of 1 kg/s until the first sensation of pain. 3 measures with 30-seconds rest between them will be performed, taking the average as Pain Pressure Threshold.
Changes in Pain Pressure Threshold
Time frame: From Baseline at 1 month
Two Pain Pressure Thresholds will be measured by a handheld algometer, one over the most painful area (peripheric hyperalgesia) and the other one over the middle of the distal phalanx of the thumb (central hyperalgesia). The Pain Pressure Threshold will be applied with the algometer perpendicular to the skin increasing at a rate of 1 kg/s until the first sensation of pain. 3 measures with 30-seconds rest between them will be performed, taking the average as Pain Pressure Threshold.
21 secondary outcomes
Beck Depression Inventory
Time frame: Baseline
Beck Depression Inventory
Time frame: At 2 weeks from Baseline
Beck Depression Inventory
Time frame: At 1 month from Baseline
State-Trait Anxiety Inventory
Time frame: Baseline
State-Trait Anxiety Inventory
Time frame: At 2 weeks from Baseline
State-Trait Anxiety Inventory
Time frame: At 1 month from Baseline
Tampa Scale of Kinesiophobia
Time frame: Baseline
Tampa Scale of Kinesiophobia
Time frame: At 2 weeks from Baseline
Tampa Scale of Kinesiophobia
Time frame: At 1 month from Baseline
Pain Catastrophizing Scale
Time frame: Baseline
Pain Catastrophizing Scale
Time frame: At 2 weeks from Baseline
Pain Catastrophizing Scale
Time frame: At 1 month from Baseline
Unified Parkinson´s Disease Rating Scale
Time frame: Baseline
Unified Parkinson´s Disease Rating Scale
Time frame: At 2 weeks from Baseline
Unified Parkinson´s Disease Rating Scale
Time frame: At 1 month from Baseline
Reaction Times
Time frame: Baseline
Reaction Times
Time frame: At 2 weeks from Baseline
Reaction Times
Time frame: At 1 month from Baseline
Transcranial Magnetic Stimulation
Time frame: Baseline
Transcranial Magnetic Stimulation
Time frame: At 2 weeks from Baseline
Transcranial Magnetic Stimulation
Time frame: At 1 month from Baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2021.
- Background: PubMed 25904081Kalia LV, Lang AE. Parkinson's disease. Lancet. 2015 Aug 29;386(9996):896-912. doi: 10.1016/S0140-6736(14)61393-3. Epub 2015 Apr 19.
- Background: PubMed 21264941Martinez-Martin P, Rodriguez-Blazquez C, Kurtis MM, Chaudhuri KR; NMSS Validation Group. The impact of non-motor symptoms on health-related quality of life of patients with Parkinson's disease. Mov Disord. 2011 Feb 15;26(3):399-406. doi: 10.1002/mds.23462. Epub 2011 Jan 24.
- Background: PubMed 29520899Antonini A, Tinazzi M, Abbruzzese G, Berardelli A, Chaudhuri KR, Defazio G, Ferreira J, Martinez-Martin P, Trenkwalder C, Rascol O. Pain in Parkinson's disease: facts and uncertainties. Eur J Neurol. 2018 Jul;25(7):917-e69. doi: 10.1111/ene.13624. Epub 2018 Apr 18.
- Background: PubMed 25505880Wright DJ, Williams J, Holmes PS. Combined action observation and imagery facilitates corticospinal excitability. Front Hum Neurosci. 2014 Nov 27;8:951. doi: 10.3389/fnhum.2014.00951. eCollection 2014.
- BackgroundVourvopoulos A, Ferreira A, Bermúdez i Badia S. NeuRow: An Immersive VR Environment for Motor-Imagery Training with the Use of Brain-Computer Interfaces and Vibrotactile Feedback. 2016.
- Background: PubMed 32340585Morales Tejera D, Fernandez-Carnero J, Suso-Marti L, Cano-de-la-Cuerda R, Lerin-Calvo A, Remon-Ramiro L, La Touche R. Comparative study of observed actions, motor imagery and control therapeutic exercise on the conditioned pain modulation in the cervical spine: a randomized controlled trial. Somatosens Mot Res. 2020 Sep;37(3):138-148. doi: 10.1080/08990220.2020.1756244. Epub 2020 Apr 27.
- Background: PubMed 31354460Vourvopoulos A, Jorge C, Abreu R, Figueiredo P, Fernandes JC, Bermudez I Badia S. Efficacy and Brain Imaging Correlates of an Immersive Motor Imagery BCI-Driven VR System for Upper Limb Motor Rehabilitation: A Clinical Case Report. Front Hum Neurosci. 2019 Jul 11;13:244. doi: 10.3389/fnhum.2019.00244. eCollection 2019.
- Background: PubMed 26096067Chaudhuri KR, Rizos A, Trenkwalder C, Rascol O, Pal S, Martino D, Carroll C, Paviour D, Falup-Pecurariu C, Kessel B, Silverdale M, Todorova A, Sauerbier A, Odin P, Antonini A, Martinez-Martin P; EUROPAR and the IPMDS Non Motor PD Study Group. King's Parkinson's disease pain scale, the first scale for pain in PD: An international validation. Mov Disord. 2015 Oct;30(12):1623-31. doi: 10.1002/mds.26270. Epub 2015 Jun 11.
- Background: PubMed 30363588Perez-Lloret S, Ciampi de Andrade D, Lyons KE, Rodriguez-Blazquez C, Chaudhuri KR, Deuschl G, Cruccu G, Sampaio C, Goetz CG, Schrag A, Martinez-Martin P, Stebbins G; Members of the MDS Committee on Rating Scales Development. Rating Scales for Pain in Parkinson's Disease: Critique and Recommendations. Mov Disord Clin Pract. 2016 Jun 24;3(6):527-537. doi: 10.1002/mdc3.12384. eCollection 2016 Nov-Dec.
- Background: PubMed 27650216Imai Y, Petersen KK, Morch CD, Arendt Nielsen L. Comparing test-retest reliability and magnitude of conditioned pain modulation using different combinations of test and conditioning stimuli. Somatosens Mot Res. 2016 Sep-Dec;33(3-4):169-177. doi: 10.1080/08990220.2016.1229178. Epub 2016 Sep 20.
- Background: PubMed 32776601Santos-Garcia D, Oreiro M, Perez P, Fanjul G, Paz Gonzalez JM, Feal Painceiras MJ, Cores Bartolome C, Valdes Aymerich L, Garcia Sancho C, Castellanos Rodrigo MDM. Impact of Coronavirus Disease 2019 Pandemic on Parkinson's Disease: A Cross-Sectional Survey of 568 Spanish Patients. Mov Disord. 2020 Oct;35(10):1712-1716. doi: 10.1002/mds.28261. Epub 2020 Sep 22.
- Individual participant dataSharing planned: Yes. Individual anonymized participant data will be available to other researchers under request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Pablo Romero Muñoz, MD PhD principal investigator
Universidad Francisco de Vitoria, Facultad de Ciencias Experimentales
Josue Fernández Carnero, PT PhD principal investigator
Universidad Rey Juan Carlos
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Action Observation+Motor Imagery through BCI and Action Observation through non-related with movement illustrations in people with Parkinson Disease and Pain, run by Universidad Francisco de Vitoria at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Juan Pablo Romero Muñoz, MD PhD (+34917091400 ext. 1688, p.romero.prof@ufv.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in King´s Parkinson´s Disease Pain Scale score (time frame: From Baseline at 2 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04651478, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2021.