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

Primary Purpose

Bipolar Disorder

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Pramipexole

Placebo

About this trial

This is an interventional treatment trial for Bipolar Disorder focused on measuring Bipolar Disorder, Cognition

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Brigham and Women's Hospital
The Zucker Hillside Hospital
Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Pramipexole

Placebo

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

MATRICS Consensus Cognitive Battery

Secondary Outcome Measures

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.

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.

Brief Psychiatric Rating Scale (BPRS)

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.

Number of Participants With Suicidal Acknowledgements

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).

The Probabilistic Stimulus Selection Task

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.

The Probabilistic Stimulus Selection Task

Full Information

NCT ID

NCT02397837

First Posted

March 19, 2015

Last Updated

February 14, 2020

Sponsor

Brigham and Women's Hospital

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT02397837

Brief Title

Targeting Cognition in Bipolar Disorder With Pramipexole

Acronym

PRAM-BD

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Completed

Study Start Date

October 2014 (undefined)

Primary Completion Date

July 26, 2018 (Actual)

Study Completion Date

July 26, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Brigham and Women's Hospital

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Bipolar Disorder

Keywords

Bipolar Disorder, Cognition

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

103 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pramipexole

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pramipexole

Other Intervention Name(s)

Mirapex

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

placebo match study drug

Primary Outcome Measure Information:

Title

MATRICS Consensus Cognitive Battery

Description

Time Frame

Baseline

Title

MATRICS Consensus Cognitive Battery

Description

Time Frame

Week 6

Title

MATRICS Consensus Cognitive Battery

Description

Time Frame

Week 12

Secondary Outcome Measure Information:

Title

Young Mania Rating Scale (YMRS)

Description

Time Frame

Baseline and week 12

Title

Hamilton Rating Scale for Depression (HRSD)

Description

Time Frame

Baseline and week 12

Title

Brief Psychiatric Rating Scale (BPRS)

Description

Time Frame

Baseline and week 12

Title

Number of Participants With Suicidal Acknowledgements

Description

Time Frame

up to Week 12

Title

The Probabilistic Stimulus Selection Task

Description

Time Frame

Baseline

Title

The Probabilistic Stimulus Selection Task

Description

Time Frame

Week 6

Title

The Probabilistic Stimulus Selection Task

Description

Time Frame

Week 12

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Katherine Burdick, PhD

Organizational Affiliation

Icahn School of Medicine at Mount Sinai

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Anil Malhotra, MD

Organizational Affiliation

The Zucker Hillside Hospital, North Shore LIJ- Health System

Official's Role

Principal Investigator

Facility Information:

Facility Name

Brigham and Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

The Zucker Hillside Hospital

City

Glen Oaks

State/Province

New York

ZIP/Postal Code

11004

Country

United States

Facility Name

Icahn School of Medicine at Mount Sinai

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22152405

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.

Results Reference

background

PubMed Identifier

14992985

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.

Results Reference

background

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Targeting Cognition in Bipolar Disorder With Pramipexole

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