Clinical trial NCT02397837: Targeting Cognition in Bipolar Disorder With Pramipexole
Official title: Pramipexole in Bipolar Disorder: Targeting Cognition (PRAM-BD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Keywords: Bipolar Disorder
Cognition
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: The Zucker Hillside Hospital
name: Northwell Health
name: National Institute of Mental Health (NIMH)
name: Icahn School of Medicine at Mount Sinai
First posted: 2015-03-25
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: MATRICS Consensus Cognitive Battery
timeFrame: Baseline
measure: MATRICS Consensus Cognitive Battery
timeFrame: Week 6
measure: MATRICS Consensus Cognitive Battery
timeFrame: Week 12
Secondary outcomes:
measure: Young Mania Rating Scale (YMRS)
timeFrame: Baseline and week 12
measure: Hamilton Rating Scale for Depression (HRSD)
timeFrame: Baseline and week 12
measure: Brief Psychiatric Rating Scale (BPRS)
timeFrame: Baseline and week 12
measure: Number of Participants With Suicidal Acknowledgements
timeFrame: up to Week 12
measure: The Probabilistic Stimulus Selection Task
timeFrame: Baseline
measure: The Probabilistic Stimulus Selection Task
timeFrame: Week 6
measure: The Probabilistic Stimulus Selection Task
timeFrame: Week 12
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Glen Oaks
country: United States
facility: The Zucker Hillside Hospital
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Katherine Burdick, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Zucker Hillside Hospital, North Shore LIJ- Health System
name: Anil Malhotra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.