Targeting Cognition in Bipolar Disorder With Pramipexole

Brigham and Women's Hospital103 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Conditions

Bipolar Disorder

Interventions

PramipexoleDRUG

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

PlaceboDRUG

placebo match study drug

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (3)

Brigham and Women's Hospital

Boston, Massachusetts, United States

The Zucker Hillside Hospital

Glen Oaks, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Outcomes

Primary Outcomes

MATRICS Consensus Cognitive Battery

MATRICS Consensus Cognitive Battery (MCCB) as measure of Neurocognitive/Functional Measures is a standardized battery designed to measure cognitive functioning in people with schizophrenia. The MCCB is represented as a composite T score. This T-score scale has a mean of 50 and a standard deviation of 10, where higher scores reflect better performance.

Time frame: Baseline

MATRICS Consensus Cognitive Battery

Time frame: Week 6

MATRICS Consensus Cognitive Battery

Time frame: Week 12

Secondary Outcomes

Young Mania Rating Scale (YMRS)

Mean change of symptoms of mania throughout the study. YMRS contains 7 items rated from 0 (symptom absent) to 4 (severe symptom) and 4 items scored 0 (symptom absent) to 8 (severe symptom), with total range from 0 to 60, where higher score indicates manic symptoms.

Time frame: Baseline and week 12

Hamilton Rating Scale for Depression (HRSD)

Mean change of symptoms of depression throughout the study. HRSD consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe), with a total score range of 0-56, where higher score indicates more depressive symptoms.

Data from ClinicalTrials.gov

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