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Completed

NCT Number: NCT02397837

Targeting Cognition in Bipolar Disorder With Pramipexole

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.

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Key information

Conditions

Bipolar Disorder Bipolar and Related Disorders Mental Disorders Mood Disorders

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Brigham and Women's Hospital, Boston, Massachusetts, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Pramipexole

Drug

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

Other names: Mirapex

Placebo

Drug

placebo match study drug

Primary outcomes

  1. MATRICS Consensus Cognitive Battery

    Time frame: Baseline

    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.

  2. MATRICS Consensus Cognitive Battery

    Time frame: Week 6

    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.

  3. MATRICS Consensus Cognitive Battery

    Time frame: Week 12

    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.

Secondary outcomes

  1. Young Mania Rating Scale (YMRS)

    Time frame: Baseline and week 12

    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.

  2. Hamilton Rating Scale for Depression (HRSD)

    Time frame: Baseline and week 12

    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.

  3. Brief Psychiatric Rating Scale (BPRS)

    Time frame: Baseline and week 12

    Mean change for positive symptoms throughout the study. BPRS consists of 18 items, each defined by a series of symptoms. Each item is rated on a 7-point scale, ranging from 1 (not observed) to 7 (very severe), with a total score range from 18-126, where higher scores indicate psychiatric symptoms.

  4. Number of Participants With Suicidal Acknowledgements

    Time frame: up to Week 12

    Number of individual participants who acknowledged at least one item on the Columbia Suicide Severity Rating Scale (C-SSRS) over the 12-week study period. Examples of items on the scale are suicidal ideation (having thoughts, planning) and suicidal behavior (preparing, attempting).

  5. The Probabilistic Stimulus Selection Task

    Time frame: Baseline

    The probabilistic selection task assesses the tendency to learn from positive versus negative outcomes. In the probabilistic stimulus selection task, participants are trained to choose one of two paired stimuli; three sets of paired stimuli are shown in total (AB, CD, and EF) and are presented randomly during the training period. To minimize verbal encoding, stimuli are Japanese Hiragana characters. Probabilistic feedback regarding the "correct" choice is provided. We report the mean percentage of accuracy on choosing the correct paired stimuli among the two treatment groups.

  6. The Probabilistic Stimulus Selection Task

    Time frame: Week 6

    The probabilistic selection task assesses the tendency to learn from positive versus negative outcomes. In the probabilistic stimulus selection task, participants are trained to choose one of two paired stimuli; three sets of paired stimuli are shown in total (AB, CD, and EF) and are presented randomly during the training period. To minimize verbal encoding, stimuli are Japanese Hiragana characters. Probabilistic feedback regarding the "correct" choice is provided. We report the mean percentage of accuracy on choosing the correct paired stimuli among the two treatment groups.

  7. The Probabilistic Stimulus Selection Task

    Time frame: Week 12

    The probabilistic selection task assesses the tendency to learn from positive versus negative outcomes. In the probabilistic stimulus selection task, participants are trained to choose one of two paired stimuli; three sets of paired stimuli are shown in total (AB, CD, and EF) and are presented randomly during the training period. To minimize verbal encoding, stimuli are Japanese Hiragana characters. Probabilistic feedback regarding the "correct" choice is provided. We report the mean percentage of accuracy on choosing the correct paired stimuli among the two treatment groups.

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Collaborators

  • Icahn School of Medicine at Mount Sinai
  • National Institute of Mental Health (NIMH)
  • Northwell Health
  • The Zucker Hillside Hospital

Registry information

Official study title

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

Acronym: PRAM-BD

Important dates

Study start
2014
Primary completion
2018
Study completion
2018
First posted
Mar 25, 2015
Registry last updated
Feb 28, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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