Pramipexole to Enhance Social Connections

Depression Clinical Trial

Official title:

Targeting Dopamine-Mediated Social Reward Sensitivity to Remediate Social Disconnection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06269146
• Other study ID #: 806035
• Secondary ID: 1R61MH129380-01
• Status: Recruiting
• Phase: Phase 2
• Start date: May 13, 2024
• Est. completion date: March 2025

Study information

• Verified date: May 2024
• Source: University of California, San Diego
• Contact: Margaret Satchwell, BS
• Phone: 858-822-4357
• Email: mksatchwell[@]health.ucsd.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study seeks to understand if the medication pramipexole improves social connectedness and functioning in adults (ages 18-50) who experience anxiety or depression. The study plans to enroll 108 participants total across two sites (University of California San Diego and New York State Psychiatric Institute). Pramipexole will be given in a 6-week randomized, double-blind, placebo-controlled trial. Social reward processing will be assessed using measures of brain function (fMRI), behavior, and self-report at baseline and week 6. Knowledge gained from this study will help determine the therapeutic potential of targeting the dopamine system to remediate social disconnection as an anxiety and depression intervention.

Description:

This study seeks to understand how modulating functioning of the neurotransmitter dopamine affects brain circuits, behaviors, and subjective experiences that are believed to underlie an individual's motivation to establish and maintain positive social connections. This knowledge will help advance understanding of brain mechanisms that can be used to better treat social functioning impairments in people experiencing anxiety or depression. The R61 phase project will evaluate the effects of pramipexole (a medication that increases dopamine signaling in the brain) on responses to different types of positive social cues or contexts. The study drug will be given in a 6-week randomized, double-blind, placebo-controlled trial for individuals with clinical levels of anxiety or depression. Aim 1 will test the hypothesis that pramipexole increases the anticipation of social rewards compared to placebo. Aim 2 will determine which dose of pramipexole (1.0 or 2.5 mg/d) produces a greater effect on social reward anticipation. To achieve these aims, approximately 108 participants (ages 18-50) with clinically elevated anxiety or depression will be randomized across two sites and randomized in equal proportions to one of two doses of pramipexole (1.0 mg/d or 2.5 mg/d) or placebo. They will complete standardized paradigms assessing social reward processing using measures of brain function (fMRI), behavior, and self-report at baseline and week 6. Knowledge gained from this study will help determine the therapeutic potential of targeting the dopamine system to remediate social disconnection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Clinically elevated levels of anxiety (OASIS = 8) or depression or (PHQ-9 = 10).

2. Moderate or greater social disability assessed with self-rating (SDS - Social = 5).

3. Below the normative mean for temperamental reward sensitivity (ATQ - Approach < 32).

4. Age 18-50.

5. Ability to provide written informed consent.

6. English proficiency. Exclusion Criteria: Exclusion criteria are included to ensure that participation does not place subjects at

undue risk, and to minimize confounding interpretation of our findings:

1. Current, imminent risk of suicide assessed with Clinical Interview and Columbia Suicide Severity Rating Scale (C-SSRS) "yes" response to items 4, 5, or 6.

2. History of bipolar or psychotic disorders.

3. History of major neurological disorder or moderate to severe traumatic brain injury.

4. History of severe or unstable medical conditions that might be compromised by participation in the study (e.g., cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease; history of seizure disorder).

5. Past 6-month substance use disorder (any severity), with the exception of mild alcohol or tobacco use disorder, which will be permitted in the study.

6. History of impulse control problems (e.g., pathological gambling).

7. First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder or bipolar disorder.

8. History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine) in the past 6 months.

9. History of dopaminergic drug use in the past 6 months.

10. Positive urinalysis screen for psychoactive drug use (that is not physician prescribed).

11. Abnormal and clinically relevant blood count, liver, renal or EKG findings as determined by physician.

12. Women who are pregnant, breastfeeding, or planning to become pregnant within the next 6 months. Individuals of childbearing potential must agree to use an acceptable method of contraception from at least 21 days prior to the first dose of study drug and for 3 months after the last dose of study drug for study entry.

13. Concurrent empirically supported psychosocial treatments for anxiety or mood disorders (e.g., cognitive behavioral therapy).

14. Use of any psychotropic medication (e.g. SSRIs, benzodiazepines) within 14 days before study entry [except for fluoxetine within 30 days]. Concurrent use is prohibited during the study

15. Anticipated inability to attend regular study appointments.

16. Anticipated inability to complete the study procedures as determined by study personnel.

17. Clinical conditions assessed by the interviewer that necessitate more imminent clinical care. These criteria are in place so participants with these other, more severe symptoms can be referred for appropriate services (e.g. self-injurious behavior or exposure to a severe traumatic event in the past week).

18. Non-correctable vision or hearing problems, as some tests require intact sensory functioning.

19. No telephone or easy access to telephone.

20. MRI contraindications

21. CGI-S score of 6 or 7.

Related Conditions & MeSH terms

• Anxiety
• Anxiety Disorders
• Depression

Intervention

Drug:
• Pramipexole Pill
The study drug, pramipexole, is an FDA-approved medication for the treatment of Parkinson's and restless leg syndrome. Pramipexole (Mirapex) tablets are taken orally, with or without food.
• Placebo Pill
Placebo will match the study drug in mode of administration, color, size, and taste.

Locations

Country	Name	City	State
United States	New York State Psychiatric Institute	New York	New York
United States	University of California, San Diego	San Diego	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Diego	National Institute of Mental Health (NIMH), New York State Psychiatric Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Negative affect in response to the social affiliation task	The state version of the Positive and Negative Affect Schedule (PANAS) will be used to measure current ("right now") negative affect before (anticipatory) and after (responsiveness) the social affiliation task. Items are answered on a 5 point scale, 1 (Very slightly or not at all) to 5 (Extremely). The negative affect scale ranges from 10-50; higher scores indicate greater levels of negative affect.	Baseline, week 6
Other	Neural activation during social punishment anticipation	Blood oxygen level dependent (BOLD) response during anticipation of negative valence social cues vs. baseline in the anterior insula and amygdala region of interest (ROI) mask, defined according to a meta-analysis of the social incentive delay task.	Baseline, week 6
Other	Social avoidance goals during the social affiliation task	Participants will rate 5 items describing avoidance-oriented goals focused on avoiding negative outcomes during the interaction. Items are answered on a 7-point scale with anchors of not at all and very much with higher scores indicating greater social avoidance goals.	Baseline, week 6
Other	Anxious behavior during the social affiliation task	Observer-rated participant behavior during the social affiliation task using items reflecting the anxiety-related behaviors commonly displayed during social-evaluative stress (e.g., fidget, appear tense or rigid). Items are rated on a 7-point scale from not at all to very much. Higher scores reflect greater anxious behavior.	Baseline, week 6
Primary	Neural activation during social reward anticipation	The primary outcome of interest is blood oxygen level dependent (BOLD) response during anticipation of positive valence social cues vs. baseline in the striatum region of interest (ROI) mask, defined according to a meta-analysis of the social incentive delay task.	Baseline, week 6
Secondary	Neural activation during opportunities to disclose to others	Blood oxygen level dependent (BOLD) response in the striatum region of interest (ROI) mask, defined according to a meta-analysis of the social incentive delay task, during share vs. private conditions of the disclosure task.	Baseline, week 6
Secondary	Motivation to engage in shared experiences with others	Participants will make choices about whether to watch the same (Shared) vs. a different (Solo) videoclip from their partner. Each option is paired with a small monetary payoff that varies across options and trials. The point of subjective equivalence will be used to quantify the relative payoff difference at which people are indifferent to the two options (0 = maximizing monetary payoff; scores < 0 represent greater value assigned to sharing experiences).	Baseline, week 6
Secondary	Positive affect in response to the social affiliation task	The state version of the Positive and Negative Affect Schedule (PANAS) will be used to measure current ("right now") positive affect before (anticipatory) and after (responsiveness) the social affiliation task. Items are answered on a 5 point scale, 1 (Very slightly or not at all) to 5 (Extremely). The positive affect scale ranges from 10-50; higher scores indicate greater levels of positive affect.	Baseline, week 6
Secondary	Social approach goals during the social affiliation task	Participants will rate 5 items describing approach-oriented goals focused on obtaining positive outcomes during the interaction. Items are answered on a 7-point scale with anchors of not at all and very much with higher scores indicating greater social approach goals.	Baseline, week 6
Secondary	Social approach behavior during the social affiliation task	Observers will rate participant behavior on self-disclosure (the degree of personal information, thoughts, and feelings revealed) and responsiveness (verbal and nonverbal displays reflecting understanding, engagement, and validation). Items are answered on a 7 point scale, 1 (not at all) to 7(very much) with higher scores indicating greater levels of social approach behavior.	Baseline, week 6
Secondary	Future approach motivation	The Desire for Future Interaction Scale (DFI) measures the degree to which respondents would be willing to affiliate with their conversation partner again. Items are answered on a 7 point scale, 1 (not at all) to 7 (very much) with higher scores indicating higher levels of future approach motivation.	Baseline, week 6
Secondary	Blood plasma pramipexole concentrations		Week 6