Parkinson DiseaseNCT05119075
Psychological Effects of Levodopa in Parkinson's Disease
A study testing Dopaminergic OFF-drug state and Dopaminergic ON-drug state in people with Parkinson Disease, run by Insel Gruppe AG, University Hospital Bern at 4 sites in Switzerland.
Trial summary
The investigators aim is to study neuropsychiatric symptoms and underlying abnormalities in resting-state fMRI in patients with Parkinson's disease (PD) suffering from neuropsychiatric fluctuations, to enhance the understanding of the pathophysiological mechanisms underlying neuropsychiatric symptoms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Dopaminergic OFF-drug state and Dopaminergic ON-drug state
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 4 sitesSwitzerland
- Study dates
- 10 Nov 2021to 31 Mar 2024
- 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
- Adults above 18 years old
- Male or female
- Diagnosed with Parkinson's disease
- Able to understand instructions, neuropsychological tests and provide written informed consent
- Able to understand the locally used language of the experimental site and speak fluently
- Presence of neuropsychiatric fluctuations, defined as the sum ≥ 3 of items included in the Ardouin Scale of Behaviour in Parkinson's Disease (ASBPD) part 2
Who cannot join
- Structural brain disease other than Parkinson's disease
- Substance abuse and/or dependence (other than DRT)
- Ongoing depression with suicidal ideation
- Severe tremors/dyskinesia/ interfering with MRI performance
- Participating in a pharmacological study
- Inability to provide informed consent (legal guardianship)
- MRI contraindications
- Pregnancy
Trial locations and contacts
4 sites in 1 country.
Switzerland4 sites
University Hospital Inselspital, Berne
Bern, 3010
EPFL Campus Biotech
Geneva, 1202
EPFL Institute of Bioengineering
Geneva, 1202
University Hospital Geneva (HUG)
Geneva, 1205
About this study
Official title: Unravelling the Impact of Levodopa on Dysfunctional Brain Networks in Parkinson's Disease With Neuropsychiatric Fluctuations
The investigators aim is to study neuropsychiatric symptoms and underlying abnormalities in resting-state fMRI in patients with Parkinson's disease (PD) suffering from neuropsychiatric fluctuations, to enhance the understanding of the pathophysiological mechanisms underlying neuropsychiatric symptoms.
Read the detailed description
Parkinson's disease (PD) is primarily classified and known as a movement disorder characterized by tremor, bradykinesia and rigidity. However, clinical examination and research have shown that PD extensively affects other systems as well, giving rise to non-motor symptoms (NMS) such as anxiety, sleep disorders, apathy, depression, cognitive impairment, and hallucinations. These non-motor fluctuations (NMF) represent a main source of disability in PD and among those, neuropsychiatric fluctuations are the most frequent. During the dopaminergic OFF-drug state anxiety, apathy, and depression are common, whereas during the dopaminergic ON-drug state euphoria, well-being, impulse control disorders (ICD) and other behavioral addictions, mania, and psychosis might occur.
Despite the severe consequences associated with dopaminergic modulation, the understanding of the pathophysiological mechanisms of neuropsychiatric symptoms is still limited and better detection and more effective treatments are needed. Fluctuating PD is a very powerful model allowing to study opposite psychiatric states intra-individually in both levodopa dopaminergic ON- and OFF-drug state, allowing to abstract many interpersonal variables.
Neurotechnology and advanced neuroimaging techniques can improve the understanding of the neural basis and brain mechanisms of specific neuropsychiatric symptoms in PD. In particular, dynamic functional connectivity (FC) analysis characterizes functional abnormalities from resting state (rs)-fMRI not only in terms of brain activations, but also of whole-brain functional networks and the transitions between maps of activations. The temporal evolution of these networks, assessed with dynamic FC approaches, has recently shown to be relevant in several clinical contexts.
Therefore, the investigators long-term goal is to identify specific resting-state signatures/biomarkers for the individual neuropsychiatric PD symptoms related to disease in dopaminergic OFF-drug state (depression, anxiety, apathy, fatigue, shame, bradyphrenia) and to dopaminergic treatment in dopaminergic ON-drug state (mania, impulse control disorders, hallucinations, psychosis, creative thinking), which might be used in the future as a proxy for the measurement of neuropsychiatric symptoms/fluctuations and thus to assess the effectiveness of specific therapies.
- Conditions
- Parkinson Disease
- Being tested
- Dopaminergic OFF-drug state, Dopaminergic ON-drug state
- Keywords
- Neuropsychiatric fluctuations, Creativity, Shame, Embarrassment, Non-motor symptoms, Hallucinations, Bradyphrenia
- Medical subject headings
- Parkinson Disease, Hallucinations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dopaminergic OFF-drug stateOther
Dopaminergic OFF-drug state: Overnight withdrawal of dopaminergic antiparkinsonian drugs during visit 3 or 4. The sequence of drug conditions (dopaminergic OFF-drug/ON-drug state or ON-drug/OFF-drug state) will be randomized.
Dopaminergic ON-drug stateOther
Dopaminergic ON-drug state: Patient will be evaluated in his/her regular treatment in dopaminergic ON-drug state at visit 3 or 4. The sequence of drug conditions (dopaminergic OFF-drug/ON-drug state or ON-drug/OFF-drug state) will be randomized.
| Study group | Role | What they receive |
|---|---|---|
| Dopaminergic ON-drug state first, dopaminergic OFF-drug state second | Experimental | The following examinations and assessments will be performed at visit 3 on regular treatment in dopaminergic ON-drug state and at visit 4 in dopaminergic OFF-drug state (overnight withdrawal of all antiparkinsonian drugs):
* MRI assessment,
* Cognitive, neuropsychiatric and neurological assessment,
* Robot-induced hallucinations through sensorimotor stimulation. Receives: Other: Dopaminergic OFF-drug state; Other: Dopaminergic ON-drug state |
| Dopaminergic OFF-drug state first, dopaminergic ON-drug state second | Experimental | The following examinations and assessments will be performed at visit 3 in dopaminergic OFF-drug state (overnight withdrawal of all antiparkinsonian drugs) and at visit 4 on regular treatment in dopaminergic ON-drug state:
* MRI assessment,
* Cognitive, neuropsychiatric and neurological assessment,
* Robot-induced hallucinations through sensorimotor stimulation. Receives: Other: Dopaminergic OFF-drug state; Other: Dopaminergic ON-drug state |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation of functional connectivity abnormalities with neuropsychiatric fluctuations
Score on the Neuropsychiatric Fluctuations Scale (NFS)
Measured: ≤ 6 weeks
Correlation of functional connectivity abnormalities with shame
Score on the Shame Visual Analogic Scale
Measured: ≤ 6 weeks
Correlation of functional connectivity abnormalities with hallucinations
Score on robot-induced presence hallucination (PH) ratings
Measured: ≤ 6 weeks
Correlation of functional connectivity abnormalities with bradyphrenia
Score on the Bradyphrenia Scale
Measured: ≤ 6 weeks
Correlation of functional connectivity abnormalities with creativity
Score on the Creative Thinking Scale
Measured: ≤ 6 weeks
Secondary outcomes (4)
The role of dopamine on hallucinations
Measurement of the influence of dopamine on hallucinations using the robot-induced presence hallucination (PH) ratings. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more hallucinations are experienced by patients.
Measured: ≤ 6 weeks
The role of dopamine on creativity
Measurement of the influence of dopamine on the Creative Thinking Scale. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more creative the patients are.
Measured: ≤ 6 weeks
The role of dopamine on shame
Measurement of the influence of dopamine on the Shame Visual Analogic Scale. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more shame patients feel.
Measured: ≤ 6 weeks
The role of dopamine on bradyphrenia
Measurement of the influence of dopamine on the bradyphrenia scale. Assessments will be performed under the two conditions (dopaminergic ON and OFF drug state) and compared. The higher the score, the more bradyphrenic the patients are.
Measured: ≤ 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2021
- Study start10 Nov 2021
- Primary completion31 Mar 2024
- Study completion31 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Geneva, Ecole Polytechnique Fédérale de Lausanne
- Responsible party
- Sponsor
- Investigators
- Paul Krack, Prof., Principal investigator, Insel Gruppe AG, University Hospital Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05119075
- Sponsor's protocol ID
- 2021-01608
- Status last verified
- Apr 2025
- First submitted
- 28 Sep 2021
- Last updated
- 13 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unravelling the Impact of Levodopa on Dysfunctional Brain Networks in Parkinson's Disease With Neuropsychiatric Fluctuations
- ClinicalTrials.gov ID
- NCT05119075
- Acronym / sponsor ID
- 2021-01608
- Conditions
- Parkinson Disease
- Keywords
- Neuropsychiatric fluctuations, Creativity, Shame, Embarrassment, Non-motor symptoms, Hallucinations, Bradyphrenia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- University Hospital, Geneva, Ecole Polytechnique Fédérale de Lausanne
- Study start
- 10 Nov 2021 (actual)
- Primary completion
- 31 Mar 2024 (actual)
- Study completion
- 31 Mar 2024 (actual)
- First posted
- 12 Nov 2021 (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.
The investigators aim is to study neuropsychiatric symptoms and underlying abnormalities in resting-state fMRI in patients with Parkinson's disease (PD) suffering from neuropsychiatric fluctuations, to enhance the understanding of the pathophysiological mechanisms underlying neuropsychiatric symptoms.
Detailed description
Parkinson's disease (PD) is primarily classified and known as a movement disorder characterized by tremor, bradykinesia and rigidity. However, clinical examination and research have shown that PD extensively affects other systems as well, giving rise to non-motor symptoms (NMS) such as anxiety, sleep disorders, apathy, depression, cognitive impairment, and hallucinations. These non-motor fluctuations (NMF) represent a main source of disability in PD and among those, neuropsychiatric fluctuations are the most frequent. During the dopaminergic OFF-drug state anxiety, apathy, and depression are common, whereas during the dopaminergic ON-drug state euphoria, well-being, impulse control disorders (ICD) and other behavioral addictions, mania, and psychosis might occur.
Despite the severe consequences associated with dopaminergic modulation, the understanding of the pathophysiological mechanisms of neuropsychiatric symptoms is still limited and better detection and more effective treatments are needed. Fluctuating PD is a very powerful model allowing to study opposite psychiatric states intra-individually in both levodopa dopaminergic ON- and OFF-drug state, allowing to abstract many interpersonal variables.
Neurotechnology and advanced neuroimaging techniques can improve the understanding of the neural basis and brain mechanisms of specific neuropsychiatric symptoms in PD. In particular, dynamic functional connectivity (FC) analysis characterizes functional abnormalities from resting state (rs)-fMRI not only in terms of brain activations, but also of whole-brain functional networks and the transitions between maps of activations. The temporal evolution of these networks, assessed with dynamic FC approaches, has recently shown to be relevant in several clinical contexts.
Therefore, the investigators long-term goal is to identify specific resting-state signatures/biomarkers for the individual neuropsychiatric PD symptoms related to disease in dopaminergic OFF-drug state (depression, anxiety, apathy, fatigue, shame, bradyphrenia) and to dopaminergic treatment in dopaminergic ON-drug state (mania, impulse control disorders, hallucinations, psychosis, creative thinking), which might be used in the future as a proxy for the measurement of neuropsychiatric symptoms/fluctuations and thus to assess the effectiveness of specific therapies.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dopaminergic ON-drug state first, dopaminergic OFF-drug state second | Experimental | Other: Dopaminergic OFF-drug state, Other: Dopaminergic ON-drug stateThe following examinations and assessments will be performed at visit 3 on regular treatment in dopaminergic ON-drug state and at visit 4 in dopaminergic OFF-drug state (overnight withdrawal of all antiparkinsonian drugs): * MRI assessment, * Cognitive, neuropsychiatric and neurological assessment, * Robot-induced hallucinations through sensorimotor stimulation. |
| Dopaminergic OFF-drug state first, dopaminergic ON-drug state second | Experimental | Other: Dopaminergic OFF-drug state, Other: Dopaminergic ON-drug stateThe following examinations and assessments will be performed at visit 3 in dopaminergic OFF-drug state (overnight withdrawal of all antiparkinsonian drugs) and at visit 4 on regular treatment in dopaminergic ON-drug state: * MRI assessment, * Cognitive, neuropsychiatric and neurological assessment, * Robot-induced hallucinations through sensorimotor stimulation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adults above 18 years old
- Male or female
- Diagnosed with Parkinson's disease
- Able to understand instructions, neuropsychological tests and provide written informed consent
- Able to understand the locally used language of the experimental site and speak fluently
Key exclusion criteria (8 listed)
- Structural brain disease other than Parkinson's disease
- Substance abuse and/or dependence (other than DRT)
- Ongoing depression with suicidal ideation
- Severe tremors/dyskinesia/ interfering with MRI performance
- Participating in a pharmacological study
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 |
|---|---|---|
| Dopaminergic OFF-drug stateDopaminergic OFF-drug state: Overnight withdrawal of dopaminergic antiparkinsonian drugs during visit 3 or 4. The sequence of drug conditions (dopaminergic OFF-drug/ON-drug state or ON-drug/OFF-drug state) will be randomized. | Other | Dopaminergic OFF-drug state first, dopaminergic ON-drug state second, Dopaminergic ON-drug state first, dopaminergic OFF-drug state second |
| Dopaminergic ON-drug stateDopaminergic ON-drug state: Patient will be evaluated in his/her regular treatment in dopaminergic ON-drug state at visit 3 or 4. The sequence of drug conditions (dopaminergic OFF-drug/ON-drug state or ON-drug/OFF-drug state) will be randomized. | Other | Dopaminergic OFF-drug state first, dopaminergic ON-drug state second, Dopaminergic ON-drug state first, dopaminergic OFF-drug state second |
Primary outcome
Correlation of functional connectivity abnormalities with neuropsychiatric fluctuations
Time frame: ≤ 6 weeks
Score on the Neuropsychiatric Fluctuations Scale (NFS)
Correlation of functional connectivity abnormalities with shame
Time frame: ≤ 6 weeks
Score on the Shame Visual Analogic Scale
Correlation of functional connectivity abnormalities with hallucinations
Time frame: ≤ 6 weeks
Score on robot-induced presence hallucination (PH) ratings
Correlation of functional connectivity abnormalities with bradyphrenia
Time frame: ≤ 6 weeks
Score on the Bradyphrenia Scale
Correlation of functional connectivity abnormalities with creativity
Time frame: ≤ 6 weeks
Score on the Creative Thinking Scale
4 secondary outcomes
The role of dopamine on hallucinations
Time frame: ≤ 6 weeks
The role of dopamine on creativity
Time frame: ≤ 6 weeks
The role of dopamine on shame
Time frame: ≤ 6 weeks
The role of dopamine on bradyphrenia
Time frame: ≤ 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2025.
- 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.
Paul Krack, Prof. principal investigator
Insel Gruppe AG, University Hospital Bern
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dopaminergic OFF-drug state and Dopaminergic ON-drug state in people with Parkinson Disease, run by Insel Gruppe AG, University Hospital Bern at 4 sites in Switzerland.
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 6 inclusion and 8 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: finished, as of the sponsor's last update on 13 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Switzerland. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Correlation of functional connectivity abnormalities with neuropsychiatric fluctuations (time frame: ≤ 6 weeks). The study lists 5 primary outcomes in all. 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 13 Apr 2025.