Social Decision Making in Parkinson's Disease

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04249544

Collaborator

United States Department of Defense (U.S. Fed)

Enrollment

Location

Arms

44.9

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Drug: Pramipexole Drug: Placebo	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Dec 3, 2019

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

The change in a harm aversion cognitive moral decision-making task [two weeks]
change in harm aversion from off drug visit to on drug visit
change in blood flow in the ventral striatum per ASL images [two weeks]
change in CBF from off drug visit to on drug visit

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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