Stratified Pharmacological Approaches for Regulating Circuit-Level Effects

Phase 2

Not yet recruiting

• Conditions: Depression - Major Depressive Disorder
• Interventions: Drug: Pramipexole Immediate Release

• Registration Number: NCT07022405
• Lead Sponsor: Stanford University

Brief Summary

This research study aims to understand how people with depression respond to the medication pramipexole and to determine whether clinical response differs depending on the function of specific circuits in the brain. The investigators hope to learn which circuits are involved in depression and how these circuits interact with pramipexole to affect mood, behavior, and cognition.

Eligible participants will undergo an 8-week treatment course of pramipexole followed by a 2-week down taper and follow up. The ultimate goal is to offer people experiencing depression a medication that is alternative to ones that may not have worked in the past and to apply the knowledge the investigators gain from investigating the brain circuits involved in depression to help personalize treatment.

The investigators invite anyone who has recently experienced symptoms of depression to participate. A prior diagnosis of depression is not required.

Detailed Description

Participants will be asked to attend up to two in-person testing visits and commit to 10 weeks of treatment and remote participation.

The in-person testing visit at the beginning of the study lasts up to 4 hours. During this visit participants will undergo a non-invasive functional magnetic resonance imaging (fMRI) brain scan, complete game-like tasks in the scanner, and answer questions regarding emotional health.

Treatment involves an 8-week course of pramipexole and followed by a 2-week down taper and follow-up. During this 10-week period, participants will meet remotely with a study coordinator or study clinician each week to answer questions about medication side effects and emotional health and to complete online surveys to monitor mood.

Sign up online or contact the investigators to learn more about participating in this study.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-06
• Study First Submitted QC: 2025-06-06
• Study First Posted: 2025-06-15
• Last Update Submitted: 2025-06-18
• Last Update Posted: 2025-06-24
• Study Start: 2025-08-01
• Primary Completion: 2030-08
• Study Completion: 2030-08-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• 18-65 years old (inclusive)
• Fluent and literate in English, with non-impaired intellectual abilities to ensure adequate comprehension of the task instructions.
• Willing to provide written, informed consent.
• Functional magnetic resonance imaging (fMRI) scanning eligibility. All participants will need to successfully complete the screening forms at the Stanford Center for Cognitive and Neurobiological Imaging (CNI).
• Patient Health Questionnaire-8 (PHQ-8) >/= 10
• Meet the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnostic criteria for current or recurrent nonpsychotic Major Depressive Disorder (MDD) established by the Mini International Neuropsychiatric Interview (MINI)

Exclusion Criteria

• Suicidality with active plan or as determined clinician judgment
• Current or lifetime history of medical illness or brain injury that may interfere with assessments as determined by clinician judgment
• Severe impediment to vision, hearing, and/or hand movement likely to interfere with ability to complete the assessments, or is unable and/or unlikely to follow the study protocols as determined by clinician judgment
• Pregnant, breastfeeding or unwilling or unable to use adequate birth control throughout the study
• History of non-responsive depression to dopamine agonists
• Any contraindication to being scanned in the 3.0T fMRI scanner, such as a cardiac pacemaker or implanted device that has not been cleared for scanning
• Previous or current DSM-5 bipolar disorder (I, II, not otherwise specified), schizophrenia spectrum or other psychotic disorders, or psychosis or as determined by clinician judgment
• Previous or current diagnosis of Attention-Deficit/Hyperactivity Disorder (ADHD)
• Meeting DSM-5 criteria for current Obsessive-Compulsive Disorder (OCD) or eating disorder
• Meeting DSM-5 criteria for alcohol use disorder or substance use disorder within the last 12 months
• Clinically significant presence/history of impulsive-compulsive behaviors or control disorder including but not limited to gambling disorder within the last 12 months.
• Current use or use of psychotropic medication within the past month. (If the participant's usual treating clinician agrees with discontinuing the medication, participants may enroll after tapering off the medication under the supervision of either their usual clinician or the study clinician. A washout period of 5 half-lives-or a different duration as determined by the study clinician-must be completed before the first scan.)
• Concurrent participation in other intervention or treatment studies
• Not having a current primary care or psychiatric provider (seen within the past year)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Pramipexole Treatment Arm	Pramipexole Immediate Release	The investigators will ask eligible participants to attend up to 2 in-person testing visits and commit to 10 weeks of treatment and remote participation. The in-person testing visit at the beginning of the study lasts up to 4 hours. During this visit participants will undergo a non-invasive functional magnetic resonance imaging (fMRI) brain scan, complete game-like tasks in the scanner, and answer questions regarding emotional health. Treatment involves an 8-week course of pramipexole and followed by a 2-week down titration and follow up. During this 10-week period, participants will meet remotely with a study coordinator or study clinician each week to answer questions about medication side effects and emotional health and to complete online surveys to monitor mood.

Primary Outcome Measures

Name	Time	Method
QIDS-SR: Quick Inventory of Depressive Symptomatology Self-Report	8 weeks	The QIDS-SR (Quick Inventory of Depressive Symptomatology - Self-Report) is a self-report questionnaire designed to assess the severity of depressive symptoms over the past seven days. It includes 16 items that evaluate 9 symptom domains corresponding to the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for major depressive disorder: sad mood, concentration difficulties, self-criticism or guilt, suicidal ideation, loss of interest, low energy or fatigue, sleep disturbances, changes in appetite or weight, and psychomotor agitation or retardation. Each domain is rated on a scale from 0 to 3, with total scores ranging from 0 to 27. Scores are interpreted as follows: 0-5 indicates no depression, 6-10 mild, 11-15 moderate, 16-20 severe, and 21-27 very severe depression. It is brief, taking approximately 5 to 10 minutes to complete.
MASQ-30: Mood Anxiety Symptom Questionnaire	8 weeks	The MASQ-30 (Mood and Anxiety Symptom Questionnaire - 30-item version) is a self-report questionnaire designed to measure symptoms of depression and anxiety. It separate symptoms that are shared between depression and anxiety from those that are more specific to each condition. The MASQ-30 includes 30 questions, divided into three main areas: Anhedonic Depression, which looks at symptoms like loss of interest or pleasure; Anxious Arousal, which focuses on physical signs of anxiety such as restlessness or a racing heart; and General Distress, which captures overall emotional discomfort common to both depression and anxiety. Each question asks how much the person has experienced a particular symptom in the past week, using a scale from 1 ("not at all") to 5 ("extremely").
Brain imaging	8 weeks	Non-invasive brain circuit quantification as assessed by functional magnetic resonance imaging metrics of activation and connectivity.
Cognitive-Emotional Behavioral Assessment	8 weeks	WebNeuro is a computerized cognitive-emotional behavioral assessment designed to objectively measure cognitive and emotional function.

Secondary Outcome Measures

Name	Time	Method
DARS: Dimensional Anhedonia Rating Scale	8 weeks	The DARS (Dimensional Anhedonia Rating Scale) is a brief, self-report tool developed to assess anhedonia, the reduced ability to experience pleasure-a key symptom in depression and other psychiatric disorders. It evaluates four domains of reward-related functioning: hobbies, food/drink, social activities, and sensory experiences (e.g., music, nature). For each domain, individuals rate items across several dimensions: interest, motivation, effort, and pleasure. Responses are given on a 5-point Likert scale, typically ranging from 0 to 4, with higher scores indicating greater engagement or enjoyment.; The full scale includes 17 items, and the total score is calculated by summing the responses, with possible scores ranging from 0 to 68. Higher total scores reflect lower levels of anhedonia. Conversely, lower scores suggest greater anhedonia
PHQ-9: Patient Health Questionnaire-9	8 weeks	The PHQ-9 (Patient Health Questionnaire-9) is a self-report screening tool designed to assess the presence and severity of depressive symptoms. It consists of 9 questions, each corresponding to one of the diagnostic criteria for major depressive disorder as outlined in the DSM. Respondents rate how often they have experienced each symptom over the past two weeks on a 4-point scale: 0 ("not at all"), 1 ("several days"), 2 ("more than half the days"), and 3 ("nearly every day"). The total score ranges from 0 to 27, with higher scores indicating more severe depressive symptoms. Scores are typically interpreted as follows: 0-4 (minimal depression), 5-9 (mild), 10-14 (moderate), 15-19 (moderately severe), and 20-27 (severe depression).
HAM-D-17: Hamilton Depression Rating Scale	8 weeks	The HAM-D-17 (Hamilton Depression Rating Scale), also known as the HDRS, is a clinician-administered assessment used to evaluate the severity of depressive symptoms in individuals diagnosed with depression. Each item is rated based on a structured interview, focusing on symptoms such as depressed mood, insomnia, anxiety, appetite disturbance, and suicidal ideation. Most items are scored on a scale from 0 to 4 or 0 to 2, depending on the symptom, with the total score ranging from 0 to 52 in the 17-item version. Interpretation of scores is generally as follows: 0-7 is considered normal or in remission, 8-13 indicates mild depression, 14-18 moderate, 19-22 severe, and 23 or higher very severe depression.
SWLS: Satisfaction With Life Scale	8 weeks	The Satisfaction With Life Scale (SWLS) is a brief, self-report questionnaire used to assess an individual's cognitive evaluation of life satisfaction. It consists of 5 items, each rated on a 7-point Likert scale ranging from 1 ("strongly disagree") to 7 ("strongly agree"), resulting in a total score ranging from 5 to 35. Higher scores indicate greater life satisfaction. The SWLS does not assess specific domains (e.g., health or work) but instead provides a broad measure of perceived well-being.
WHOQoL-BREF: The World Health Organization Quality of Life - BREF	8 weeks	The World Health Organization Quality of Life - BREF (WHOQOL-BREF) was developed by the World Health Organization to assess an individual's perceived quality of life. It includes 26 items that ask about a person's physical health, psychological well-being, social relationships, and environment. Each item is rated on a 5-point scale, with higher scores indicating a more positive perception of that area of life. The responses are grouped into four domain scores: Physical Health, Psychological Health, Social Relationships, and Environment. Scores for each domain are calculated and then transformed to a scale from 0 to 100, with higher scores reflecting better quality of life. The WHOQOL-BREF provides a broad yet efficient snapshot of how individuals feel about their overall well-being and daily functioning.

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States