Stratified Pharmacological Approaches for Regulating Circuit-Level Effects

NCT ID: NCT07022405

Last Updated: 2025-06-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-31

Study Completion Date

2030-08-31

Brief Summary

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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

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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.

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Conditions

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Depression - Major Depressive Disorder

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pramipexole Treatment Arm

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.

Group Type EXPERIMENTAL

Pramipexole Immediate Release

Intervention Type DRUG

The intervention involves taking pramipexole immediate release (IR) for 8 weeks followed by 2 weeks of down titration and follow up.

Interventions

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Pramipexole Immediate Release

The intervention involves taking pramipexole immediate release (IR) for 8 weeks followed by 2 weeks of down titration and follow up.

Intervention Type DRUG

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Leanne Williams

Professor of Psychiatry and Behavioral Sciences

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Stanford University

Stanford, California, United States

Site Status

Countries

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United States

Central Contacts

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Erica Ma

Role: CONTACT

650-736-8262

Leyla Boyar

Role: CONTACT

650-498-9326

Facility Contacts

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Erica Ma

Role: primary

650-736-8262

References

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Sporn J, Ghaemi SN, Sambur MR, Rankin MA, Recht J, Sachs GS, Rosenbaum JF, Fava M. Pramipexole augmentation in the treatment of unipolar and bipolar depression: a retrospective chart review. Ann Clin Psychiatry. 2000 Sep;12(3):137-40. doi: 10.1023/a:1009060800999.

Reference Type BACKGROUND
PMID: 10984002 (View on PubMed)

Goldberg JF, Burdick KE, Endick CJ. Preliminary randomized, double-blind, placebo-controlled trial of pramipexole added to mood stabilizers for treatment-resistant bipolar depression. Am J Psychiatry. 2004 Mar;161(3):564-6. doi: 10.1176/appi.ajp.161.3.564.

Reference Type BACKGROUND
PMID: 14992985 (View on PubMed)

Lattanzi L, Dell'Osso L, Cassano P, Pini S, Rucci P, Houck PR, Gemignani A, Battistini G, Bassi A, Abelli M, Cassano GB. Pramipexole in treatment-resistant depression: a 16-week naturalistic study. Bipolar Disord. 2002 Oct;4(5):307-14. doi: 10.1034/j.1399-5618.2002.01171.x.

Reference Type BACKGROUND
PMID: 12479663 (View on PubMed)

Inoue T, Kitaichi Y, Masui T, Nakagawa S, Boku S, Tanaka T, Suzuki K, Nakato Y, Usui R, Koyama T. Pramipexole for stage 2 treatment-resistant major depression: an open study. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Dec 1;34(8):1446-9. doi: 10.1016/j.pnpbp.2010.07.035. Epub 2010 Aug 11.

Reference Type BACKGROUND
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Hori H, Kunugi H. The efficacy of pramipexole, a dopamine receptor agonist, as an adjunctive treatment in treatment-resistant depression: an open-label trial. ScientificWorldJournal. 2012;2012:372474. doi: 10.1100/2012/372474. Epub 2012 Aug 1.

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Dell'Osso B, Ketter TA. Assessing efficacy/effectiveness and safety/tolerability profiles of adjunctive pramipexole in bipolar depression: acute versus long-term data. Int Clin Psychopharmacol. 2013 Nov;28(6):297-304. doi: 10.1097/YIC.0b013e3283639015.

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Strejilevich SA, Martino DJ, Igoa A, Manes F. Pathological gambling in a bipolar patient treated with pramipexole. J Neuropsychiatry Clin Neurosci. 2011 Winter;23(1):E2-3. doi: 10.1176/jnp.23.1.jnpe2. No abstract available.

Reference Type BACKGROUND
PMID: 21304118 (View on PubMed)

El-Mallakh RS, Penagaluri P, Kantamneni A, Gao Y, Roberts RJ. Long-term use of pramipexole in bipolar depression: a naturalistic retrospective chart review. Psychiatr Q. 2010 Sep;81(3):207-13. doi: 10.1007/s11126-010-9130-6.

Reference Type BACKGROUND
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Cassano P, Lattanzi L, Soldani F, Navari S, Battistini G, Gemignani A, Cassano GB. Pramipexole in treatment-resistant depression: an extended follow-up. Depress Anxiety. 2004;20(3):131-8. doi: 10.1002/da.20038.

Reference Type BACKGROUND
PMID: 15549689 (View on PubMed)

Takahashi M, Nishida S, Nakamura M, Kobayashi M, Matsui K, Ito E, Usui A, Inoue Y. Restless legs syndrome augmentation among Japanese patients receiving pramipexole therapy: Rate and risk factors in a retrospective study. PLoS One. 2017 Mar 6;12(3):e0173535. doi: 10.1371/journal.pone.0173535. eCollection 2017.

Reference Type BACKGROUND
PMID: 28264052 (View on PubMed)

Perugi G, Toni C, Ruffolo G, Frare F, Akiskal H. Adjunctive dopamine agonists in treatment-resistant bipolar II depression: an open case series. Pharmacopsychiatry. 2001 Jul;34(4):137-41. doi: 10.1055/s-2001-15872.

Reference Type BACKGROUND
PMID: 11518474 (View on PubMed)

Aiken CB. Pramipexole in psychiatry: a systematic review of the literature. J Clin Psychiatry. 2007 Aug;68(8):1230-6.

Reference Type BACKGROUND
PMID: 17854248 (View on PubMed)

Zarate CA Jr, Payne JL, Singh J, Quiroz JA, Luckenbaugh DA, Denicoff KD, Charney DS, Manji HK. Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry. 2004 Jul 1;56(1):54-60. doi: 10.1016/j.biopsych.2004.03.013.

Reference Type BACKGROUND
PMID: 15219473 (View on PubMed)

Corrigan MH, Denahan AQ, Wright CE, Ragual RJ, Evans DL. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety. 2000;11(2):58-65. doi: 10.1002/(sici)1520-6394(2000)11:23.0.co;2-h.

Reference Type BACKGROUND
PMID: 10812530 (View on PubMed)

Chaudhuri KR, Rizos A, Sethi KD. Motor and nonmotor complications in Parkinson's disease: an argument for continuous drug delivery? J Neural Transm (Vienna). 2013 Sep;120(9):1305-20. doi: 10.1007/s00702-013-0981-5. Epub 2013 Mar 2.

Reference Type BACKGROUND
PMID: 23456290 (View on PubMed)

Drijgers RL, Verhey FR, Tissingh G, van Domburg PH, Aalten P, Leentjens AF. The role of the dopaminergic system in mood, motivation and cognition in Parkinson's disease: a double blind randomized placebo-controlled experimental challenge with pramipexole and methylphenidate. J Neurol Sci. 2012 Sep 15;320(1-2):121-6. doi: 10.1016/j.jns.2012.07.015. Epub 2012 Jul 22.

Reference Type BACKGROUND
PMID: 22824349 (View on PubMed)

Miura S, Kida H, Nakajima J, Noda K, Nagasato K, Ayabe M, Aizawa H, Hauser M, Taniwaki T. Anhedonia in Japanese patients with Parkinson's disease: analysis using the Snaith-Hamilton Pleasure Scale. Clin Neurol Neurosurg. 2012 May;114(4):352-5. doi: 10.1016/j.clineuro.2011.11.008. Epub 2011 Dec 2.

Reference Type BACKGROUND
PMID: 22137783 (View on PubMed)

Fujiwara S, Kimura F, Hosokawa T, Ishida S, Sugino M, Hanafusa T. Anhedonia in Japanese patients with Parkinson's disease. Geriatr Gerontol Int. 2011 Jul;11(3):275-81. doi: 10.1111/j.1447-0594.2010.00678.x. Epub 2011 Jan 17.

Reference Type BACKGROUND
PMID: 21241445 (View on PubMed)

Hamidovic A, Kang UJ, de Wit H. Effects of low to moderate acute doses of pramipexole on impulsivity and cognition in healthy volunteers. J Clin Psychopharmacol. 2008 Feb;28(1):45-51. doi: 10.1097/jcp.0b013e3181602fab.

Reference Type BACKGROUND
PMID: 18204340 (View on PubMed)

Lemke MR, Brecht HM, Koester J, Kraus PH, Reichmann H. Anhedonia, depression, and motor functioning in Parkinson's disease during treatment with pramipexole. J Neuropsychiatry Clin Neurosci. 2005 Spring;17(2):214-20. doi: 10.1176/jnp.17.2.214.

Reference Type BACKGROUND
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Reichmann H, Brecht MH, Koster J, Kraus PH, Lemke MR. Pramipexole in routine clinical practice: a prospective observational trial in Parkinson's disease. CNS Drugs. 2003;17(13):965-73. doi: 10.2165/00023210-200317130-00003.

Reference Type BACKGROUND
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Fawcett J, Rush AJ, Vukelich J, Diaz SH, Dunklee L, Romo P, Yarns BC, Escalona R. Clinical Experience With High-Dosage Pramipexole in Patients With Treatment-Resistant Depressive Episodes in Unipolar and Bipolar Depression. Am J Psychiatry. 2016 Feb 1;173(2):107-11. doi: 10.1176/appi.ajp.2015.15060788. No abstract available.

Reference Type BACKGROUND
PMID: 26844792 (View on PubMed)

Other Identifiers

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5U01MH136062-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

80975

Identifier Type: -

Identifier Source: org_study_id

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