Targeting Cognition in Bipolar Disorder With Pramipexole (PRAM-BD)

Mass General Brigham

Status and phase: Completed; Phase 4

Conditions: Bipolar Disorder

Treatments: Drug: Pramipexole; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02397837

2017P001185

1R01MH102309 (U.S. NIH Grant/Contract)

1R01MH102257 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 103 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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103 participants in 2 patient groups, including a placebo group

Pramipexole

Experimental group

Description:

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.

Treatment:

Drug: Pramipexole

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo