Social Decision Making in Parkinson's Disease

Study Overview
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Brief Summary
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Impulsive and compulsive behaviors occur in up to 46% of Parkinson's Disease (PD) patients taking dopamine agonist (DAA) medications. While these abnormal social behaviors have been studied in other neurodegenerative disorders, the true incidence of social problems, and the relationship to dopamine therapy, in PD patients remains unknown. This study is aiming to determine if dopamine agonists alter social decision-making and to determine if impaired social decision-making relates to dopamine-induced mesolimbic network dysfunction in PD patients. The protocol will include a screening visit, and on-DAA visit, and an off-DAA visit. For both the on and off DAA visits, participants will continue taking Carbidopa-Levodopa, but will withdrawal off of other PD related medications. Both visits will include an MRI, fMRI shock task, questionnaires to be filled out by other the participant and the caregiver, moral-decision making computer tasks, and the Unified Parkinsons Disease Rating Scale (UPDRS) part II and III. For the on-DAA visit, participants will take Pramipexole. For the off-DAA visit, participants will receive a placebo. Participants will remind blinded to which medication they are receiving that day and will be counterbalanced such that all participants will not take the Pramipexole or placebo on the same days.

Detailed Description
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Impulsive and compulsive behaviors occur in up to 46% of Parkinson's Disease (PD) patients taking dopamine agonist (DAA) medications. While these abnormal social behaviors have been studied in other neurodegenerative disorders, the true incidence of social problems, and the relationship to dopamine therapy, in PD patients remains unknown. This study is aiming to determine if dopamine agonists alter social decision-making and to determine if impaired social decision-making relates to dopamine-induced mesolimbic network dysfunction in PD patients. The protocol will include a screening visit, and on-DAA visit, and an off-DAA visit. For both the on and off DAA visits, participants will continue taking Carbidopa-Levodopa, but will withdrawal off of other PD related medications to reduce circulating drugs and residual drug effects. Both visits will include an MRI, fMRI shock task, questionnaires to be filled out by other the participant and the caregiver, moral-decision making computer tasks, and the Unified Parkinson's Disease Rating Scale (UPDRS) part II and III. For the on-DAA visit, participants will take Carbidopa-Levodopa 1 hour before the scan and will take 1mg of Pramipexole 1 hour before the scan. For the off-DAA visit, participants will take Carbidopa-Levodopa 1 hour before the scan and will take a placebo 1 hour before the scan. Participants will remind blinded to which medication they are receiving that day and will be counterbalanced such that all participants will not take the Pramipexole or placebo on the same days.

Official Title
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Cognitive and Neural Mechanisms of Impaired Social Decision-Making in Parkinson's Patients Taking Dopamine Agonists

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Pramipexole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 45-80 Ability to give informed consent Idiopathic Parkinson's disease Currently taking dopamine agonist therapy Mild symptom severity (Hoehn & Yahr ≤ 3) Disease duration of <12 years Demonstrated positive response to dopamine therapy Exclusion Criteria: Medications classes that influence GABA concentrations: benzodiazepines, cholinesterase inhibitors, antipsychotics, opioids, and MAO inhibitors History of substance abuse or use of any psychostimulants (other than caffeine) in the last 6 months or more than 4 times in lifetime Current tobacco (or nicotine use) or alcohol intake greater than 8 ounces of whiskey or equivalent per week Comorbid neurological disorders (e.g., stroke, peripheral neuropathy, seizure disorder) or history of head trauma (other than a single concussion) Unstable medical condition, [e.g., diabetes or pulmonary disease, significant medical condition, including high blood pressure (systolic B.P. > 135, Diastolic B.P. > 85), or any hepatic, renal, cardiovascular, hematological, endocrine or ophthalmological condition] History of major psychiatric illness (including any affective disorder, substance use disorder, psychotic disorder, or eating disorder) Dementia Deep brain stimulation Contraindications to 3 Tesla MRI, e.g., extreme obesity, claustrophobia, cochlear implant, metal fragments in eyes, cardiac pacemaker, neural stimulator, tattoos with iron pigment and metallic body inclusions or other metal implanted in the body Dyskinesia or tremor that would cause severe motion artifact during MRI scan Clear indication of secondary gain

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Impulsive group, placebo then pramipexole<br>half of the impulsive group will first get the placebo on the first day and pramipexole on the second day | Drug: Pramipexole<br>* 1mg of pramipexole<br>Drug: Placebo<br>* 1mg equivalent of placebo<br>|
| Experimental: Impulsive group, pramipexole then placebo<br>half of the impulsive group will first get the pramipexole on the first day and the placebo on the second day | Drug: Pramipexole<br>* 1mg of pramipexole<br>Drug: Placebo<br>* 1mg equivalent of placebo<br>|
| Experimental: Non-impulsive group, placebo then pramipexole<br>half of the non-impulsive group will first get the placebo on the first day and the pramipexole on the second day | Drug: Pramipexole<br>* 1mg of pramipexole<br>Drug: Placebo<br>* 1mg equivalent of placebo<br>|
| Experimental: Non-impulsive, pramipexole then placebo<br>half of the non-impulsive group will first get the pramipexole on the first day and the placebo on the second day | Drug: Pramipexole<br>* 1mg of pramipexole<br>Drug: Placebo<br>* 1mg equivalent of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in a harm aversion cognitive moral decision-making task | change in harm aversion from off drug visit to on drug visit | two weeks | 
| change in blood flow in the ventral striatum per ASL images | change in CBF from off drug visit to on drug visit | two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Impulsive behavior, Social decision making, Moral decision making, dopamine agonists