Cognitive Enhancement in Bipolar Disorder

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00597896

Enrollment

Registered

2008-01-18

Start date

2005-10-31

Completion date

2011-04-30

Last updated

2015-06-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bipolar Disorder

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.

Interventions

DRUGpramipexole

po pramipexole versus matching placebo minimum 0.125 mg bid and maximum 0.75 mg bid

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline to Week 8 in Controlled Oral Word Association Test (COWAT) Letter Fluency	Change from Baseline to Week 8	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.
Change From Baseline to Week 8 in d2 Test of Attention	Change from Baseline to Week 8	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	Change from Baseline to Week 8	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 Weschler Adult Intelligence Scale-Third Edition (WAIS-III) Digit Span Subtest (Digits Forward)	Change from Baseline to Week 8	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)	Change from Baseline to Week 8	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	Change from Baseline to Week 8	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	Change from Baseline to Week 8	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	Change from Baseline to Week 8	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	Change from Baseline to Week 8	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.

Secondary

Measure	Time frame	Description
Double-blind: Change From Baseline in Clinician-Administered Rating Scale for Mania (CARS-M)Total Score at Endpoint	Change from Baseline to Week 8	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.
Double-blind: Change From Baseline in Hamilton Rating Scale for Depression (HAM-D-21) Total Score at Endpoint	Change from Baseline to Week 8	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Active Pramipexole 0.125 mg BID-0.75 mg BID - pramipexole	21
Placebo Pramipexole 0.125 mg BID-0.75 mg BID - matching placebo	24
Total	45

Baseline characteristics

Characteristic	Placebo Pramipexole	Active Pramipexole	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	24 Participants	21 Participants	45 Participants
Age, Continuous	44.42 years STANDARD_DEVIATION 12.2	43.81 years STANDARD_DEVIATION 9.4	44.14 years STANDARD_DEVIATION 10.9
Region of Enrollment United States	24 participants	21 participants	45 participants
Sex: Female, Male Female	10 Participants	14 Participants	24 Participants
Sex: Female, Male Male	14 Participants	7 Participants	21 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 21	0 / 24
serious Total, serious adverse events	2 / 21	1 / 24

Outcome results

Primary

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.

Time frame: Change from Baseline to Week 8