Trial Outcomes & Findings for Targeting Cognition in Bipolar Disorder With Pramipexole (NCT NCT02397837)

Last Updated: 2020-02-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

103 participants

Primary outcome timeframe

Baseline

Results posted on

2020-02-28

Participant Flow

Protocol enrollment of 103 is the total number of participants who signed a consent form. 63 were randomized to a treatment group. The discrepancy between 103 and 63 is the total number of participants who completed a screen visit but failed to randomize (N=40).

Participant milestones

Participant milestones
Measure	Pramipexole 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo 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. Placebo: placebo match study drug
Overall Study STARTED	33	30
Overall Study COMPLETED	26	24
Overall Study NOT COMPLETED	7	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Pramipexole 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo 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. Placebo: placebo match study drug
Overall Study Withdrawal by Subject	6	5
Overall Study Physician Decision	1	1

Baseline Characteristics

Targeting Cognition in Bipolar Disorder With Pramipexole

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pramipexole n=33 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=30 Participants 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. Placebo: placebo match study drug	Total n=63 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	33 Participants n=5 Participants	30 Participants n=7 Participants	63 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	17 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants	26 Participants n=7 Participants	51 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	14 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	14 Participants n=7 Participants	33 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	33 Participants n=5 Participants	30 Participants n=7 Participants	63 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline

Outcome measures

Outcome measures
Measure	Pramipexole n=33 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=30 Participants 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. Placebo: placebo match study drug
MATRICS Consensus Cognitive Battery	35.45 T-score Standard Deviation 12.33	38.07 T-score Standard Deviation 10.45

PRIMARY outcome

Timeframe: Week 6

Population: The discrepancy in participants analyzed here compared to baseline is due to an early termination from study of 5 participants in pramipexole group and 4 participants in placebo group.

Outcome measures

Outcome measures
Measure	Pramipexole n=28 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=26 Participants 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. Placebo: placebo match study drug
MATRICS Consensus Cognitive Battery	35.57 T-score Standard Deviation 13.87	39.81 T-score Standard Deviation 11.01

PRIMARY outcome

Timeframe: Week 12

Outcome measures

Outcome measures
Measure	Pramipexole n=26 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=24 Participants 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. Placebo: placebo match study drug
MATRICS Consensus Cognitive Battery	36.46 T-score Standard Deviation 13.61	41.50 T-score Standard Deviation 11.47

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Average change in YMRS based on baseline and week 12 score.

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.

Outcome measures

Outcome measures
Measure	Pramipexole n=33 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=30 Participants 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. Placebo: placebo match study drug
Young Mania Rating Scale (YMRS)	-0.92 score on a scale Standard Deviation 2.21	-0.57 score on a scale Standard Deviation 1.88

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Average change in HRSD based on baseline and week 12 score.

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.

Outcome measures

Outcome measures
Measure	Pramipexole n=33 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=30 Participants 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. Placebo: placebo match study drug
Hamilton Rating Scale for Depression (HRSD)	-0.24 score on a scale Standard Deviation 3.78	-.22 score on a scale Standard Deviation 3.66

SECONDARY outcome

Timeframe: Baseline and week 12

Population: Average change in BPRS based on baseline and week 12 score.The discrepancy in participants analyzed here compared to participant flow is due to available data.

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.

Outcome measures

Outcome measures
Measure	Pramipexole n=32 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=29 Participants 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. Placebo: placebo match study drug
Brief Psychiatric Rating Scale (BPRS)	-0.63 score on a scale Standard Deviation 3.53	-0.61 score on a scale Standard Deviation 3.70

SECONDARY outcome

Timeframe: up to Week 12

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).

Outcome measures

Outcome measures
Measure	Pramipexole n=33 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=30 Participants 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. Placebo: placebo match study drug
Number of Participants With Suicidal Acknowledgements	0 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline

Population: The discrepancy in participants analyzed from participants in Participant Flow is due to availability of data because of software issues in running 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.

Outcome measures

Outcome measures
Measure	Pramipexole n=18 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=21 Participants 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. Placebo: placebo match study drug
The Probabilistic Stimulus Selection Task	56.94 percentage of accuracy Standard Deviation 17.00	67.56 percentage of accuracy Standard Deviation 20.12

SECONDARY outcome

Timeframe: Week 6

Population: The discrepancy in participants analyzed from participants in Participant Flow is due to availability of data because of software issues in running task.

Outcome measures

Outcome measures
Measure	Pramipexole n=19 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=18 Participants 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. Placebo: placebo match study drug
The Probabilistic Stimulus Selection Task	56.91 percentage of accuracy Standard Deviation 22.60	56.94 percentage of accuracy Standard Deviation 22.67

SECONDARY outcome

Timeframe: Week 12

Population: The discrepancy in participants analyzed from participants in Participant Flow is due to availability of data because of software issues in running task.

Outcome measures

Outcome measures
Measure	Pramipexole n=19 Participants 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=19 Participants 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. Placebo: placebo match study drug
The Probabilistic Stimulus Selection Task	59.54 percentage of accuracy Standard Deviation 21.59	50.99 percentage of accuracy Standard Deviation 16.04

Adverse Events

Pramipexole

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Katherine Burdick

Brigham and Women's Hospital

Phone: 617-732-5789

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Pramipexole n=33 participants at risk 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week study.	Placebo n=30 participants at risk 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. Placebo: placebo match study drug
Gastrointestinal disorders Nausea/Vomiting	6.1% 2/33 • Number of events 2 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	6.7% 2/30 • Number of events 2 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
Skin and subcutaneous tissue disorders Rash	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
General disorders Headache	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
General disorders Poor Coordination	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
General disorders Dizziness	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
Eye disorders Blurred Vision	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	3.3% 1/30 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
Ear and labyrinth disorders Ringing in Ears	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	6.7% 2/30 • Number of events 2 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
Renal and urinary disorders Painful Urination	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
Reproductive system and breast disorders Menstrual Irregularity	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
General disorders Difficulty Sleeping	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
Psychiatric disorders Anxiety	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
General disorders Poor Concentration	6.1% 2/33 • Number of events 2 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
General disorders General malaise	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
General disorders Fatigue	3.0% 1/33 • Number of events 1 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
General disorders Decreased Energy	6.1% 2/33 • Number of events 2 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).	0.00% 0/30 • Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).