Cognitive Enhancement in Bipolar Disorder

This study has been completed.
Sponsor:
Collaborator:
Stanley Medical Research Institute
Information provided by (Responsible Party):
Ray, Susan, North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier:
NCT00597896
First received: January 8, 2008
Last updated: June 10, 2015
Last verified: June 2015
  Purpose

The purpose of this study is to examine whether the medication pramipexole (Mirapex) may be able to improve cognitive problems (i.e. difficulties with thinking, memory, and concentration) that may be associated with bipolar disorder.


Condition Intervention Phase
Bipolar Disorder
Drug: pramipexole
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cognitive Enhancement in Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by North Shore Long Island Jewish Health System:

Primary Outcome Measures:
  • Change From Baseline to Week 8 in Weschler Adult Intelligence Scale-Third Edition (WAIS-III) Digit Span Subtest (Digits Forward) [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    The examinee is read a sequence of numbers and must recall the numbers in the same order. Measures auditory attention and verbal working memory. The standard scores were reported for this measure. Values indicate the change from baseline to week 8, with positive values reflecting higher scores at week 8 and negative values reflecting lower scores at week 8.

  • Change From Baseline to Week 8 in Weschler Adult Intelligence Scale-Third Edition (WAIS-III) Digit Span Subtest (Digits Backward) [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    The examinee is read a sequence of numbers and must recall the numbers in reverse order. Measures auditory attention and verbal working memory. The standard scores were reported for this measure. Values indicate the change from baseline to week 8, with positive values reflecting higher scores at week 8 and negative values reflecting lower scores at week 8.

  • Change From Baseline to Week 8 in Weschler Adult Intelligence Scale-Third Edition (WAIS-III) Digit Symbol Coding Test [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    Using a key, the examinee copies symbols that are paired with numbers within a specified time limit. Measures visual scanning and graphomotor speed. The standard scores were reported for this measure. Values indicate the change from baseline to week 8, with positive values reflecting higher scores at week 8 and negative values reflecting lower scores at week 8.

  • Change From Baseline to Week 8 in Stroop Color-Word Test [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    The Stroop Color-Word Test consists of a word page with words printed in black ink, a color page with 'Xs' printed in color, and a color-word page where the color and the word do not match. The examinee reads the words or names the ink colors as quickly as possible within a time limit. Measures selective attention and inhibitory control. The raw scores (total number of words read) for each trial were reported for this measure. Values indicate the change from baseline to week 8, with positive values reflecting higher scores at week 8 and negative values reflecting lower scores at week 8.

  • Change From Baseline to Week 8 in Trail Making Test Part A [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    The examinee is instructed to connect a set of 25 dots as quickly as possible while maintaining accuracy. Measures attentional resources and is a measure of the frontal lobe "executive" functions of visual search, set-switching and conceptual flexibility. The total time in seconds was reported for this measure. Values indicate the change from baseline to week 8, with positive values reflecting higher scores at week 8 and negative values reflecting lower scores at week 8.

  • Change From Baseline to Week 8 in Trail Making Test Part B [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    The examinee is instructed to connect a set of 25 dots, alternating between numbers and letters, as quickly as possible while maintaining accuracy. Measures attentional resources and is a measure of the frontal lobe "executive" functions of visual search, set-switching and conceptual flexibility. The total time in seconds was reported for this measure. Values indicate the change from baseline to week 8, with positive values reflecting higher scores at week 8 and negative values reflecting lower scores at week 8.

  • Change From Baseline to Week 8 in d2 Test of Attention [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    The d2 Test of Attention consist of 14 lines, each comprised of 47 characters, for a total of 658 items. The examinee must scan each line and cross out all the "d's" with two dashes. The subject is allowed 20 seconds per line. Measures rapid processing of visual information and motor speed.

  • Change From Baseline to Week 8 in Hopkins Verbal Learning Test [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    The examinee is required to recall a list of 12 words over 3 immediate learning trials, a delayed recall trial and a recognition trial. Measures learning and retention of verbal material. The total number of words recalled during the delayed recall trial was reported. Values indicate the change from baseline to week 8, with positive values reflecting higher scores at week 8 and negative values reflecting lower scores at week 8.

  • Change From Baseline to Week 8 in Controlled Oral Word Association Test (COWAT) Letter Fluency [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    The examinee is required to say as many words as they can think of in one minute that begin with a given letter of the alphabet. The task contains three trials. Measures phonetic verbal fluency. The raw score (total words recorded across the three trials) was reported. Values indicate the change from baseline to week 8, with positive values reflecting higher scores at week 8 and negative values reflecting lower scores at week 8.


Secondary Outcome Measures:
  • Double-blind: Change From Baseline in Hamilton Rating Scale for Depression (HAM-D-21) Total Score at Endpoint [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    The Hamilton Depression Rating Scale is a clinician-rated scale used to rate depression severity. The items are rated on either a 5-point (0 to 4) or a 3-point (0 to 2) scale. The 5-point scale uses a rating of 0 (absent), 1 (doubtful to mild), 2 (mild to moderate), 3 (moderate to severe), and 4 (very severe). Higher scores indicate worsening. The responses are summed to yield the HAM-D-21 score that ranges from 0-64.

  • Double-blind: Change From Baseline in Clinician-Administered Rating Scale for Mania (CARS-M)Total Score at Endpoint [ Time Frame: Change from Baseline to Week 8 ] [ Designated as safety issue: No ]
    The CARS-M is a 15-item clinician-rated scale designed to assess severity of both manic and psychotic symptoms. There are 2 subscales: a mania scale and a scale for psychotic symptoms and disorganization. There are a total of 15 items on the CARS-M, each of which is rated on a 6-point Likert scale (0/Absent to 5/Extreme), with the exception of item 15 ("Insight") which is rated on a 5-point Likert scale. These items yield two subscale scores—one for Mania (items 1-10) and one for Psychosis (items 11-15). Higher scores indicate worsening. The responses are summed to yield the CARS-M-15 score that ranges from 0-74.


Enrollment: 50
Study Start Date: October 2005
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active pramipexole
Day 1: Random assignment to drug or placebo and dosage starting at 0.125 mg BID, which will be increased every week to a target dose of 1.5 mg/day. Targeted maximum dose of 1.5 mg/day is expected to be reached by week 4, however, dosing will be flexible based upon side effects reported. The maximum dose will be 1.5 mg/day.
Drug: pramipexole
po pramipexole versus matching placebo minimum 0.125 mg bid and maximum 0.75 mg bid
Other Name: Mirapex
Placebo Comparator: Placebo pramipexole
Day 1: Random assignment to drug or placebo and dosage starting at 0.125 mg BID, which will be increased every week to a target dose of 1.5 mg/day. Targeted maximum dose of 1.5 mg/day is expected to be reached by week 4, however, dosing will be flexible based upon side effects reported. The maximum dose will be 1.5 mg/day.
Drug: pramipexole
po pramipexole versus matching placebo minimum 0.125 mg bid and maximum 0.75 mg bid
Other Name: Mirapex

Detailed Description:

To address the primary aim, the study is an eight-week, randomized, double-blind, placebo-controlled treatment trial of pramipexole in 50 euthymic bipolar I and II disorder (BPD) patients, who demonstrate cognitive impairment.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects between 18 and 65 years of age, who meet Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for BPD I or II (by SCID) and confirmed in the diagnostic consensus conference will be included.
  • Subjects must also meet criteria for euthymia described above.
  • All subjects must be taking a standard mood stabilizer at a stable therapeutic dose (i.e. lithium, carbamazepine, valproate, lamotrigine).

Exclusion Criteria:

  • Subjects with a history of central nervous system (CNS) trauma, neurological disorder, Attention Deficit Hyperactivity Disorder (ADHD), or learning disability will be excluded.
  • Subjects with a DSM-IV diagnosis of current or recent substance abuse or dependence (in the previous 1 month) will be excluded.
  • Moreover, subjects with rapid-cycling during the past year will be excluded (based on SCID).
  • Any subject with an active, unstable medical problem that may interfere with cognition will be excluded based on the investigator's judgment.
  • While medication status is an important consideration in any study of bipolar disorder, the exclusion of patients taking any medication is not practical, given the high prevalence of combination pharmacotherapy for bipolar disorder. To help control for medication effects on cognition, we plan to limit the types of medications allowed by excluding certain medications with a known impact on cognitive performance.

    • Subjects taking clozapine will be excluded due to it's potential overlapping mechanisms of action with pramipexole.
    • Subjects taking prescription or over-the counter medications may also be excluded if these medications have been shown to impact cognition (i.e. diphenhydramine).
    • The use of benzodiazepines, sedatives, or sleeping pills, within 6 hours of neurocognitive testing will not be allowed. In addition, patients taking topiramate, tricyclic antidepressants, or anticholinergic medications that are known to impact cognition will be excluded from participation.
    • Subjects taking any medications that are known to interact with pramipexole (i.e. Zantac, Tagamet, Reglan, Benemid, Probalan, Compazine, Phenergan, quinidine, selegiline, verapamil, and any other medication with a known interaction) will also be excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00597896

Locations
United States, New York
North Shore - Long Island Jewish Health System
Glen Oaks, New York, United States, 11004
Sponsors and Collaborators
North Shore Long Island Jewish Health System
Stanley Medical Research Institute
Investigators
Principal Investigator: Anil K. Malhotra, MD North Shore Long Island Jewish Health System
Principal Investigator: Katherine Burdick, PhD North Shore Long Island Jewish Health System
  More Information

Publications:
Responsible Party: Ray, Susan, Senior Research Coordinator, North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier: NCT00597896     History of Changes
Other Study ID Numbers: 05-069, 05T-670
Study First Received: January 8, 2008
Results First Received: January 4, 2013
Last Updated: June 10, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mental Disorders
Mood Disorders
Pramipexole
Anti-Dyskinesia Agents
Antioxidants
Antiparkinson Agents
Central Nervous System Agents
Dopamine Agents
Dopamine Agonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015