Back to resultsCognitive Enhancement in Bipolar Disorder
Primary Purpose
Bipolar Disorder
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
pramipexole
Sponsored by
About this trial
This is an interventional treatment trial for Bipolar Disorder
Eligibility 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.
Sites / Locations
- North Shore - Long Island Jewish Health System
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Active pramipexole
Placebo pramipexole
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Change From Baseline to Week 8 in Weschler Adult Intelligence Scale-Third Edition (WAIS-III) Digit Span Subtest (Digits Forward)
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)
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
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
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
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
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
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
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
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
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
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.
Full Information
NCT ID
NCT00597896
First Posted
January 8, 2008
Last Updated
June 10, 2015
Sponsor
Northwell Health
Collaborators
Stanley Medical Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT00597896
Brief Title
Cognitive Enhancement in Bipolar Disorder
Official Title
Cognitive Enhancement in Bipolar Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
October 2005 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Northwell Health
Collaborators
Stanley Medical Research Institute
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active pramipexole
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo pramipexole
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
pramipexole
Other Intervention Name(s)
Mirapex
Intervention Description
po pramipexole versus matching placebo minimum 0.125 mg bid and maximum 0.75 mg bid
Primary Outcome Measure Information:
Title
Change From Baseline to Week 8 in Weschler Adult Intelligence Scale-Third Edition (WAIS-III) Digit Span Subtest (Digits Forward)
Description
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.
Time Frame
Change from Baseline to Week 8
Title
Change From Baseline to Week 8 in Weschler Adult Intelligence Scale-Third Edition (WAIS-III) Digit Span Subtest (Digits Backward)
Description
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.
Time Frame
Change from Baseline to Week 8
Title
Change From Baseline to Week 8 in Weschler Adult Intelligence Scale-Third Edition (WAIS-III) Digit Symbol Coding Test
Description
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.
Time Frame
Change from Baseline to Week 8
Title
Change From Baseline to Week 8 in Stroop Color-Word Test
Description
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.
Time Frame
Change from Baseline to Week 8
Title
Change From Baseline to Week 8 in Trail Making Test Part A
Description
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.
Time Frame
Change from Baseline to Week 8
Title
Change From Baseline to Week 8 in Trail Making Test Part B
Description
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.
Time Frame
Change from Baseline to Week 8
Title
Change From Baseline to Week 8 in d2 Test of Attention
Description
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.
Time Frame
Change from Baseline to Week 8
Title
Change From Baseline to Week 8 in Hopkins Verbal Learning Test
Description
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.
Time Frame
Change from Baseline to Week 8
Title
Change From Baseline to Week 8 in Controlled Oral Word Association Test (COWAT) Letter Fluency
Description
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.
Time Frame
Change from Baseline to Week 8
Secondary Outcome Measure Information:
Title
Double-blind: Change From Baseline in Hamilton Rating Scale for Depression (HAM-D-21) Total Score at Endpoint
Description
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.
Time Frame
Change from Baseline to Week 8
Title
Double-blind: Change From Baseline in Clinician-Administered Rating Scale for Mania (CARS-M)Total Score at Endpoint
Description
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.
Time Frame
Change from Baseline to Week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anil K. Malhotra, MD
Organizational Affiliation
Northwell Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Katherine Burdick, PhD
Organizational Affiliation
Northwell Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
North Shore - Long Island Jewish Health System
City
Glen Oaks
State/Province
New York
ZIP/Postal Code
11004
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.
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Cognitive Enhancement in Bipolar Disorder
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