Multiple SclerosisNCT03219073
Transcranial Direct Current Stimulation to Lower Neuropathic Pain in People With Multiple Sclerosis
A study testing Active tDCS using tDCS device in people with Multiple Sclerosis and Neuropathic Pain, run by Thorsten Rudroff at 1 site in United States.
Trial summary
Transcranial Direct Current Stimulation (tDCS) is a noninvasive brain stimulation technique that utilizes low amplitude direct currents applied via scalp electrodes to apply currents to the brain and modulate the level of cortical excitability. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis, Neuropathic Pain
- What is being tested?
- Active tDCS using tDCS device
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2018to 1 Jul 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with Multiple Sclerosis (PwMS)
- Age range 18-65
- Expanded disability status scale comprised between 1.5 and 6.5 with relapsing remitting MS (RRMS) in remitting phase
- Presenting with chronic, drug-resistant, neuropathic pain
- Patients must score at or above a 0 on the Neuropathic Pain Questionnaire (NPQ).
- Patients must score at least a 40 mm on the visual analog scale (VAS) for pain perception at baseline
- All analgesic medications discontinued at least 24 hours before entering the study
Who cannot join
- Any change in:
- disease-modifying medications, or
- a relapse of disease symptoms within the last 60 days
- History of seizures
- History of traumatic brain injury
- History of claustrophobia
Show all 16Show fewer
- Presence of:
- pacemakers,
- aneurysm clips,
- artificial heart valves,
- metallic prostheses, or
- pregnancy.
- Recent hospitalization (within the last 3 months)
- Enforced bed rest/sedentary state
- Resting plasma glucose greater than 200 mg/dl
- Presence of other neurological disorders.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver
Aurora, Colorado, 80045
About this study
Official title: Transcranial Direct Current Stimulation to Lower Neuropathic Pain in People With Multiple Sclerosis: a Mechanistic FDG-PET Study
Transcranial Direct Current Stimulation (tDCS) is a noninvasive brain stimulation technique that utilizes low amplitude direct currents applied via scalp electrodes to apply currents to the brain and modulate the level of cortical excitability. tDCS applied over the dorsolateral prefrontal and motor cortex has been reported to be able to decrease pain sensation and to increase pain threshold in healthy subjects and is effective in reducing central chronic pain in patients with multiple sclerosis (PwMS.) In spite of the encouraging results of tDCS in PwMS, detailed mechanisms accounting for its analgesic effect have not yet been elucidated.
This will be the first study to determine the effects of tDCS on whole and regional brain activity in PwMS with neuropathic pain to identify potential mechanisms of the analgesic effects of tDCS. These findings will provide targets for future studies investigating different stimulation areas, possible short- and long-term side effects, and specific target areas for other precise stimulation techniques such as transcranial magnetic stimulation.
Read the detailed description
The investigators aim is to identify changes in brain activation following transcranial direct current stimulation (tDCS), and determine whether these changes are associated with reduced ratings of pain. The investigators hypothesize that the analgesic effects of tDCS are associated with altered glucose metabolism of key regions of the top-down pain modulatory system, such as the dorsolateral prefrontal cortex (DLPFC) and medulla.
This study will follow an interventional protocol with two groups. Upon enrollment into the study, all participants will undergo testing for the outcome measures described above. Each participant will then be randomly assigned into the SHAM or tDCS group for the study intervention. This study will be completed over the course of 6 consecutive days and 1 follow-up phone call 1 week after the final testing for each participant (total of 13 days).
Two age and sex matched groups, each n =8, will receive either tDCS or SHAM stimulation.
All of the following measures will be performed before and after the tDCS or SHAM intervention.
Fluorodeoxyglucose ([18F] FDG) - Whole and regional brain FDG uptake will be measured to determine the mechanistic effect of tDCS on brain activity.
Visual Analog Scale (VAS) - The VAS is a self-evaluation scale where the participant is asked to mark a segment that ranges from 0-100 as visually described in millimeter units where 0 mm indicates no pain and 100 mm indicates the worst possible pain. This scale has been widely used in studies that evaluated pain as an outcome measure: both validity and reproducibility have been demonstrated.
VAS for Anxiety - This is a self-evaluation scale that ranges from 0 to 100 mm: 0 mm indicates no anxiety and 100 mm indicates the worst possible anxiety.
Prior to beginning the 2nd-5th tDCS sessions, the effectiveness of tDCS will be assessed using the following procedures:
Visual Analog Scale (VAS) - Each participant will be asked how effective the previous day's tDCS session was at reducing their pain by marking a segment on the range of 0-100 as visually described in millimeter units where 0 mm indicates no reduction in pain and 100 mm indicates complete alleviation of pain.
Duration of Relief - If the participant indicates any reduction in pain following the previous day's tDCS session, the participant will be asked to estimate how long the participant's pain was reduced following the session.
One week following the post-intervention testing, participants will be contacted via telephone and asked the following questions:
- Was tDCS effective at reducing the participant's pain?
- If so, how long did the participant notice a reduction in pain following the participant's final tDCS session?
- Have the participants reduced their use of pain relieving medications since the last tDCS session?
- Conditions
- Multiple Sclerosis, Neuropathic Pain
- Being tested
- Active tDCS using tDCS device, SHAM tDCS using tDCS device
- Keywords
- multiple sclerosis, neuropathic pain, [18F] FDG-PET CT, tDCS, transcranial direct current stimulation
- Medical subject headings
- Multiple Sclerosis, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active tDCS using tDCS deviceDevice
Active tDCS using tDCS device is a noninvasive brain stimulation technique that utilizes low amplitude direct currents applied via scalp electrodes to apply currents to the brain and modulate the level of cortical excitability. tDCS applied over the dorsolateral prefrontal and motor cortex has been reported to be able to decrease pain sensation and to increase pain threshold in healthy subjects and is effective in reducing central chronic pain in PwMS.
SHAM tDCS using tDCS deviceDevice
SHAM tDCS emulates active tDCS in all but the actual stimulation. Electrodes of the tDCS device are placed in the same place as with active tDCS however no current is activated.
| Study group | Role | What they receive |
|---|---|---|
| SHAM tDCS | Sham comparator | SHAM tDCS using tDCS device will be used for sham stimulation where the electrodes will be placed in the same positions as for anodal M1 stimulation, but the stimulator will be turned off after 90 seconds. Therefore, the patients feel the initial itching sensation but receive no current for the rest of the stimulation period. Receives: Device: SHAM tDCS using tDCS device |
| Active tDCS with a tDCS device | Active comparator | Active tDCS using tDCS device (Neuroelectrics Inc., Simi Valley, CA, USA) will deliver a small direct current through two sponge surface electrodes (5cm × 5cm, soaked with 15 mM NaCL). The anodal electrode will be placed over the M1 contralateral to the worst somatic pain area (C3, EEG 10/20 system) and the cathode over the supraorbital area contralateral to the anodal electrode. A constant current of 2 mA intensity will be applied for 20 minutes once a day for 5 consecutive days. Receives: Device: Active tDCS using tDCS device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral Glucose Uptake in Patients With Multiple Sclerosis With Neuropathic Pain
Whole and regional brain glucose uptake via positron emission tomography with a glucose analogue tracer will be measured to determine the mechanistic effect of transcranial direct current stimulation on brain activity in subjects. Glucose uptake will be determined in patients with multiple sclerosis who received brain stimulation and patients with multiple sclerosis who received SHAM. The outcome variable is the mean Standardized Uptake Value.
Measured: 1 week
Secondary outcomes (2)
Change in Neuropathic Pain as Recorded on a Visual Analog Scale (VAS).
VAS Scale 0-100 The higher the worse.
Measured: 1 week
Change in Neuropathic Symptom Inventory
The neuropathic symptom inventory is a 12-item questionnaire. This is a valid and reliable measure of neuropathic pain in adults. The Neuropathic Pain Symptoms Inventory (NPSI) contains 12 items in 5 subscales. The subscales include superficial and deep spontaneous pain, paroxysmal pain, evoked pain, and dysesthesia/paresthesia. Among the 12 items, 10 are scored using a numerical rating scale (NRS), ranging from 0 to 10, assessing the severity of experienced neuropathic pain within the previous 24 hours.
Higher scores of NPSI indicate more severe peripheral neuropathy.10 is the highest score and indicates severe peripheral neuropathy.
Minimum score is 0 and the maximum score is 120.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2017
- Study start1 Feb 2018
- Primary completion16 Jun 2018
- Study completion1 Jul 2018
Why it stopped: Principal Investigator is taking appointment with another institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies 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
- Two age and sex matched groups, each n =8, will be randomized to receive either tDCS or SHAM stimulation.
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thorsten Rudroff
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Thorsten Rudroff, University of Iowa
- Investigators
- Thorsten Rudroff, Ph.D., Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03219073
- Sponsor's protocol ID
- 17-0690
- Status last verified
- Nov 2022
- First submitted
- 14 Apr 2017
- Last updated
- 29 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Direct Current Stimulation to Lower Neuropathic Pain in People With Multiple Sclerosis: a Mechanistic FDG-PET Study
- ClinicalTrials.gov ID
- NCT03219073
- Acronym / sponsor ID
- 17-0690
- Conditions
- Multiple Sclerosis, Neuropathic Pain
- Keywords
- multiple sclerosis, neuropathic pain, [18F] FDG-PET CT, tDCS, transcranial direct current stimulation
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Principal Investigator is taking appointment with another institution.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Thorsten RudroffUniversity, hospital or other
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 16 Jun 2018 (actual)
- Study completion
- 1 Jul 2018 (actual)
- First posted
- 17 Jul 2017 (actual)
- Results
- Posted 29 Nov 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Transcranial Direct Current Stimulation (tDCS) is a noninvasive brain stimulation technique that utilizes low amplitude direct currents applied via scalp electrodes to apply currents to the brain and modulate the level of cortical excitability. tDCS applied over the dorsolateral prefrontal and motor cortex has been reported to be able to decrease pain sensation and to increase pain threshold in healthy subjects and is effective in reducing central chronic pain in patients with multiple sclerosis (PwMS.) In spite of the encouraging results of tDCS in PwMS, detailed mechanisms accounting for its analgesic effect have not yet been elucidated.
This will be the first study to determine the effects of tDCS on whole and regional brain activity in PwMS with neuropathic pain to identify potential mechanisms of the analgesic effects of tDCS. These findings will provide targets for future studies investigating different stimulation areas, possible short- and long-term side effects, and specific target areas for other precise stimulation techniques such as transcranial magnetic stimulation.
Detailed description
The investigators aim is to identify changes in brain activation following transcranial direct current stimulation (tDCS), and determine whether these changes are associated with reduced ratings of pain. The investigators hypothesize that the analgesic effects of tDCS are associated with altered glucose metabolism of key regions of the top-down pain modulatory system, such as the dorsolateral prefrontal cortex (DLPFC) and medulla.
This study will follow an interventional protocol with two groups. Upon enrollment into the study, all participants will undergo testing for the outcome measures described above. Each participant will then be randomly assigned into the SHAM or tDCS group for the study intervention. This study will be completed over the course of 6 consecutive days and 1 follow-up phone call 1 week after the final testing for each participant (total of 13 days).
Two age and sex matched groups, each n =8, will receive either tDCS or SHAM stimulation.
All of the following measures will be performed before and after the tDCS or SHAM intervention.
Fluorodeoxyglucose ([18F] FDG) - Whole and regional brain FDG uptake will be measured to determine the mechanistic effect of tDCS on brain activity.
Visual Analog Scale (VAS) - The VAS is a self-evaluation scale where the participant is asked to mark a segment that ranges from 0-100 as visually described in millimeter units where 0 mm indicates no pain and 100 mm indicates the worst possible pain. This scale has been widely used in studies that evaluated pain as an outcome measure: both validity and reproducibility have been demonstrated.
VAS for Anxiety - This is a self-evaluation scale that ranges from 0 to 100 mm: 0 mm indicates no anxiety and 100 mm indicates the worst possible anxiety.
Prior to beginning the 2nd-5th tDCS sessions, the effectiveness of tDCS will be assessed using the following procedures:
Visual Analog Scale (VAS) - Each participant will be asked how effective the previous day's tDCS session was at reducing their pain by marking a segment on the range of 0-100 as visually described in millimeter units where 0 mm indicates no reduction in pain and 100 mm indicates complete alleviation of pain.
Duration of Relief - If the participant indicates any reduction in pain following the previous day's tDCS session, the participant will be asked to estimate how long the participant's pain was reduced following the session.
One week following the post-intervention testing, participants will be contacted via telephone and asked the following questions:
- Was tDCS effective at reducing the participant's pain?
- If so, how long did the participant notice a reduction in pain following the participant's final tDCS session?
- Have the participants reduced their use of pain relieving medications since the last tDCS session?
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
- Model description
- Two age and sex matched groups, each n =8, will be randomized to receive either tDCS or SHAM stimulation.
| Arm | Type | Receives |
|---|---|---|
| SHAM tDCS | Sham comparator | Device: SHAM tDCS using tDCS deviceSHAM tDCS using tDCS device will be used for sham stimulation where the electrodes will be placed in the same positions as for anodal M1 stimulation, but the stimulator will be turned off after 90 seconds. Therefore, the patients feel the initial itching sensation but receive no current for the rest of the stimulation period. |
| Active tDCS with a tDCS device | Active comparator | Device: Active tDCS using tDCS deviceActive tDCS using tDCS device (Neuroelectrics Inc., Simi Valley, CA, USA) will deliver a small direct current through two sponge surface electrodes (5cm × 5cm, soaked with 15 mM NaCL). The anodal electrode will be placed over the M1 contralateral to the worst somatic pain area (C3, EEG 10/20 system) and the cathode over the supraorbital area contralateral to the anodal electrode. A constant current of 2 mA intensity will be applied for 20 minutes once a day for 5 consecutive days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with Multiple Sclerosis (PwMS)
- Age range 18-65
- Expanded disability status scale comprised between 1.5 and 6.5 with relapsing remitting MS (RRMS) in remitting phase
- Presenting with chronic, drug-resistant, neuropathic pain
- Patients must score at or above a 0 on the Neuropathic Pain Questionnaire (NPQ).
Key exclusion criteria (16 listed)
- Any change in:
- History of seizures
- History of traumatic brain injury
- History of claustrophobia
- Presence of:
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 |
|---|---|---|
| Active tDCS using tDCS deviceActive tDCS using tDCS device is a noninvasive brain stimulation technique that utilizes low amplitude direct currents applied via scalp electrodes to apply currents to the brain and modulate the level of cortical excitability. tDCS applied over the dorsolateral prefrontal and motor cortex has been reported to be able to decrease pain sensation and to increase pain threshold in healthy subjects and is effective in reducing central chronic pain in PwMS. | Device | Active tDCS with a tDCS device |
| SHAM tDCS using tDCS deviceSHAM tDCS emulates active tDCS in all but the actual stimulation. Electrodes of the tDCS device are placed in the same place as with active tDCS however no current is activated. | Device | SHAM tDCS |
Primary outcome
Cerebral Glucose Uptake in Patients With Multiple Sclerosis With Neuropathic Pain
Time frame: 1 week
Whole and regional brain glucose uptake via positron emission tomography with a glucose analogue tracer will be measured to determine the mechanistic effect of transcranial direct current stimulation on brain activity in subjects. Glucose uptake will be determined in patients with multiple sclerosis who received brain stimulation and patients with multiple sclerosis who received SHAM. The outcome variable is the mean Standardized Uptake Value.
2 secondary outcomes
Change in Neuropathic Pain as Recorded on a Visual Analog Scale (VAS).
Time frame: 1 week
Change in Neuropathic Symptom Inventory
Time frame: 1 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Thorsten Rudroff, Ph.D. principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active tDCS using tDCS device in people with Multiple Sclerosis and Neuropathic Pain, run by Thorsten Rudroff at 1 site in United States.
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 7 inclusion and 16 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: stopped early, as of the sponsor's last update on 29 Nov 2022. 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 United States. 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?
Yes. Results are posted in the registry (first posted 29 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cerebral Glucose Uptake in Patients With Multiple Sclerosis With Neuropathic Pain (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Nov 2022.