Targeting Cognition in Bipolar Disorder With Pramipexole

NCT ID: NCT02397837

Last Updated: 2020-02-28

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

103 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-31

Study Completion Date

2018-07-26

Brief Summary

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Converging evidence suggests that patients with bipolar disorder suffer from deficits in neurocognitive functioning that persist, despite remission of acute affective symptoms. These impairments contribute directly to functional disability, highlighting the need for interventions above and beyond standard treatments in order to achieve a full inter-episode recovery. The current study aims to investigate the safety and efficacy of a dopamine agonist (pramipexole), on these persistent cognitive abnormalities in euthymic bipolar patients using a placebo-controlled, adjunctive, 12-week trial design.

Detailed Description

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All eligible participants will undergo study visits at screening, baseline (week 0), week 1, week 2, week 3, week 4, week 6, week 8, and week 12, (end of study).

Randomization will be conducted via a computer generated program and all study staff will be blinded unless un-blinding is required for safety reasons. Subjects will be randomized on a 1:1 ratio with stratification for concomitant antipsychotic status and depression at baseline (HRSD \<8 vs \> 8). Study drug will be blinded and matched to placebo. Adapting from our previous work in BD and according to package labeling, the dosage titration schedule will be slow and flexible. Dosing will be initiated at 0.25 mg QHS on night one, followed by 0.25 mg BID day two onward, and increased every week to a target of 4.5 mg/day. As compared with our previous maximum 1.5 mg/day (Burdick et al. 2012), we opted to allow up to 4.5 mg/day (the maximum approved dosage in Parkinson's disease) to ensure adequate target engagement. We are familiar with this dose range, as 4.5 mg/day was allowed in our study in BD depression (Goldberg et al. 2004). Dosing will be flexible based on side effects; however, if 1.5 mg/day cannot be tolerated, the subject will be discontinued. Titration will occur up to week 6 and then efforts will be made to maintain the same dose until the completion of the trial (week 12).

Conditions

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Bipolar Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Pramipexole

Pramipexole, by mouth. Dosing will be initiated at 0.25 mg on night one, followed by 0.25 mg twice-a-day day two onward, and increased every week to a target of 4.5 mg/day for the 12-week duration of the study.

Group Type EXPERIMENTAL

Pramipexole

Intervention Type DRUG

Up to 4.5mg, PO, (by mouth) per day of the 12-week study.

Placebo

Placebo, by mouth. Dosing will be initiated at 0.25 mg on night one, followed by 0.25 mg twice-a-day day two onward, and increased every week to a target of 4.5 mg/day for the 12-week duration of the study.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

placebo match study drug

Interventions

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Pramipexole

Up to 4.5mg, PO, (by mouth) per day of the 12-week study.

Intervention Type DRUG

Placebo

placebo match study drug

Intervention Type DRUG

Other Intervention Names

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Mirapex

Eligibility Criteria

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Inclusion Criteria

* Age 18-65
* DSM-IV BD I or II diagnosis
* Affective stability, defined by a Young Mania Rating Scale (YMRS) rating of \< 8 and a Hamilton Depression Rating Scale (HRSD) rating of \< 16 at screening and baseline. We will further require that any subsyndromal depression has not significantly worsened in the 4 weeks prior to randomization so as to avoid enrolling subjects who are on the verge of a full depressive episode.
* Evidence of clinically-significant neurocognitive impairment at screening
* Clinically-acceptable, stably-dosed, mood stabilizing medication regimen for \> 1 month prior to enrollment, with no medication changes planned over the 12-week study period.

Exclusion Criteria

* History of CNS trauma, neurological disorder, ADHD, or learning disability
* Positive urine toxicology or DSM-IV diagnosis of substance abuse/dependence within 3 months
* Active, unstable medical problem that may interfere with cognition
* Recent history of rapid-cycling
* Abnormal lab or ECG result at screen
* History of heart failure
* Significant suicidal risk (HRSD item 3 \> 2 or by clinical judgment)
* Estimated IQ in MR range as per Wide Range Achievement Test (WRAT) standard score of less than 70
* Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (including oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy)
* Women who are breastfeeding
* Participation in any other investigational cognitive enhancement study within 30 days
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Zucker Hillside Hospital

OTHER

Sponsor Role collaborator

Northwell Health

OTHER

Sponsor Role collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Katherine Burdick

Lead Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Katherine Burdick, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Anil Malhotra, MD

Role: PRINCIPAL_INVESTIGATOR

The Zucker Hillside Hospital, North Shore LIJ- Health System

Locations

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Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

The Zucker Hillside Hospital

Glen Oaks, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Countries

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United States

References

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Burdick KE, Braga RJ, Nnadi CU, Shaya Y, Stearns WH, Malhotra AK. Placebo-controlled adjunctive trial of pramipexole in patients with bipolar disorder: targeting cognitive dysfunction. J Clin Psychiatry. 2012 Jan;73(1):103-12. doi: 10.4088/JCP.11m07299. Epub 2011 Nov 29.

Reference Type BACKGROUND
PMID: 22152405 (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)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan: Zucker Hillside Hospital Site

View Document

Document Type: Study Protocol and Statistical Analysis Plan: Brigham and Women's Hospital Site

View Document

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol and Statistical Analysis Plan: Mount Sinai School of Medicine Site

View Document

Other Identifiers

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1R01MH102257

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01MH102309

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2017P001185

Identifier Type: -

Identifier Source: org_study_id

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