Pramipexole for Depression

(SPARCLE Trial)

Overseen By Leyla Boyar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Psychotropic medications

Disqualifiers: Suicidality, Bipolar, Schizophrenia, ADHD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of pramipexole for individuals experiencing depression. Researchers aim to determine if different brain circuits influence how pramipexole alters mood and behavior. Participants will take the medication for 8 weeks, followed by a gradual discontinuation over 2 weeks. Individuals who have recently experienced depression symptoms, even without a formal diagnosis, may be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's efficacy in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

Yes, you need to stop taking any psychotropic medications (drugs that affect mood, behavior, or thinking) before joining the trial. You can enroll after tapering off these medications with your doctor's help, and you must complete a washout period (time without taking the medication) before the first scan.

Is there any evidence suggesting that pramipexole is likely to be safe for humans?

Research has shown that pramipexole is generally safe for people with depression. Studies have found that combining pramipexole with regular antidepressants can effectively and safely treat both unipolar and bipolar depression.

One study used pramipexole for 24 weeks and found it to be a safe option for individuals whose depression did not improve with other treatments. Another study also highlighted pramipexole as a safe method for addressing treatment-resistant depression.

Doctors are familiar with pramipexole, as it is already approved for other conditions. However, like any medication, it can have side effects, which will be monitored during the trial. Overall, evidence suggests that pramipexole is a reasonable choice for safely managing depression. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for depression, such as SSRIs and SNRIs, work by altering serotonin and norepinephrine levels in the brain. But pramipexole works differently, targeting the dopamine system, which offers a fresh angle on treating depression. Researchers are excited about pramipexole because it has the potential to help patients who don't respond well to standard antidepressants, possibly providing relief through a novel mechanism. Additionally, its unique action on dopamine receptors might lead to different side effect profiles, offering an alternative for those who struggle with the side effects of current medications.

What evidence suggests that pramipexole might be an effective treatment for depression?

Research has shown that pramipexole may help improve depression symptoms, particularly in people with Parkinson's disease. It has successfully reduced depression in these patients, but its comparison to traditional antidepressants remains unclear. Some studies are investigating its potential for individuals who haven't responded well to other depression treatments. While pramipexole has shown effects similar to antidepressants, more research is needed to determine its effectiveness compared to other options. Overall, pramipexole is considered an alternative for those who haven't found success with other medications. Participants in this trial will receive pramipexole to evaluate its effectiveness in treating depression. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals currently experiencing symptoms of depression, even without a prior diagnosis. It's designed to see if pramipexole can help improve mood and cognitive function by targeting specific brain circuits.

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive an 8-week course of pramipexole followed by a 2-week down taper

10 weeks

1 visit (in-person), weekly remote meetings

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Remote monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Pramipexole

Trial Overview Participants will take pramipexole immediate release for 8 weeks, followed by a 2-week tapering period. The study aims to understand how the drug interacts with brain circuits in people with depression.

How Is the Trial Designed?

Group I: Pramipexole Treatment Arm Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Citations

1. thelancet.com thelancet.com/journals/lanpsy/article/PIIS2215-0366(25)00194-4/fulltext

Pramipexole augmentation for the acute phase of treatment ... Meta-analyses by Tundo and colleagues found no significant effect of pramipexole on efficacy outcomes in patients with major depressive disorder ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11428619/

Comparative Short- and Long-Term Effectiveness ... A meta-analysis of 18 randomized controlled trials showed that pramipexole improves depressive symptoms in patients with Parkinson's disease [ ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00231959

Effectiveness of Pramipexole for Treatment-Resistant ... This study will evaluate the effectiveness of pramipexole in treating depression in individuals that have not responded to other medications.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725015290

Efficacy and tolerability of pramipexole versus ... Pramipexole alleviates depression in PD patients, but its efficacy versus typical antidepressants remain unclear. · Pramipexole shows antidepressant efficacy ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10141126/

Pramipexole Augmentation for Treatment-Resistant Unipolar ... The primary outcome measure was the treatment response, measured at the study endpoint. Results: We identified 8 studies including 281 patients ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0278584621001846

Efficacy and safety of 24-week pramipexole augmentation ... Off-label use of pramipexole as augmentation of traditional AD is an effective and safe 24 weeks treatment of resistant unipolar and bipolar depression.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03642964

A Study in Patients With Major Depressive Disorder This is a Phase 2a, placebo-controlled, single-blind study in up to 24 patients with major depressive disorder (MDD).