PRAM-BD: Targeting Cognition in Bipolar Disorder With Pramipexole

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02397837
• Collaborator: The Zucker Hillside Hospital (Other), Northwell Health (Other), National Institute of Mental Health (NIMH) (NIH), Icahn School of Medicine at Mount Sinai (Other)
• Enrollment: 103
• Locations: 3
• Arms: 2
• Duration (Months): 45.8
• Patients Per Site: 34.3
• Patients Per Site Per Month: 0.7

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder	Drug: Pramipexole; Drug: Placebo	Phase 4

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pramipexole in Bipolar Disorder: Targeting Cognition (PRAM-BD)
• Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Jul 26, 2018
• Actual Study Completion Date: Jul 26, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Pramipexole; Up to 4.5mg, PO, (by mouth) per day of the 12-week study.; Other Names: Mirapex
Placebo Comparator: 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.	Drug: Placebo; placebo match study drug

Outcome Measures

Primary Outcome Measures

1. MATRICS Consensus Cognitive Battery [Baseline]

   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.

2. MATRICS Consensus Cognitive Battery [Week 6]

   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.

3. MATRICS Consensus Cognitive Battery [Week 12]

   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.

Secondary Outcome Measures

1. Young Mania Rating Scale (YMRS) [Baseline and week 12]

   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.

2. Hamilton Rating Scale for Depression (HRSD) [Baseline and week 12]

   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.

3. Brief Psychiatric Rating Scale (BPRS) [Baseline and week 12]

   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.

4. Number of Participants With Suicidal Acknowledgements [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).

5. The Probabilistic Stimulus Selection Task [Baseline]

   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.

6. The Probabilistic Stimulus Selection Task [Week 6]

   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.

7. The Probabilistic Stimulus Selection Task [Week 12]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
2	The Zucker Hillside Hospital	Glen Oaks	New York	United States	11004
3	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029

Sponsors and Collaborators

• Brigham and Women's Hospital
• The Zucker Hillside Hospital
• Northwell Health
• National Institute of Mental Health (NIMH)
• Icahn School of Medicine at Mount Sinai

Investigators

• Principal Investigator: Katherine Burdick, PhD, Icahn School of Medicine at Mount Sinai
• Principal Investigator: Anil Malhotra, MD, The Zucker Hillside Hospital, North Shore LIJ- Health System

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan: Zucker Hillside Hospital Site - Oct 23, 2017
• Study Protocol and Statistical Analysis Plan: Brigham and Women's Hospital Site - Aug 29, 2018
• Informed Consent Form - Sep 6, 2018
• Study Protocol and Statistical Analysis Plan: Mount Sinai School of Medicine Site - May 6, 2017

More Information

Publications

• 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.
• 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.

• Responsible Party: Katherine Burdick, Lead Investigator, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT02397837
• Other Study ID Numbers: 2017P001185; 1R01MH102257; 1R01MH102309
• First Posted: Mar 25, 2015
• Last Update Posted: Feb 28, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Katherine Burdick, Lead Investigator, Brigham and Women's Hospital: Bipolar Disorder; Cognition
• Additional relevant MeSH terms: Disease; Bipolar Disorder; Pramipexole

Study Results

Participant Flow

Pre-assignment Detail	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).

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

Baseline Characteristics

Arm/Group Title	Pramipexole	Placebo	Total
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug	Total of all reporting groups
Overall Participants	33	30	63
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	33 100%	30 100%	63 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	20 60.6%	17 56.7%	37 58.7%
Male	13 39.4%	13 43.3%	26 41.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 12.1%	4 13.3%	8 12.7%
Not Hispanic or Latino	25 75.8%	26 86.7%	51 81%
Unknown or Not Reported	4 12.1%	0 0%	4 6.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	5 15.2%	1 3.3%	6 9.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 21.2%	14 46.7%	21 33.3%
White	19 57.6%	14 46.7%	33 52.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 6.1%	1 3.3%	3 4.8%
Region of Enrollment (Count of Participants)
United States	33 100%	30 100%	63 100%

Outcome Measures

1. Primary Outcome

Title	MATRICS Consensus Cognitive Battery
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
Measure Participants	33	30
Mean (Standard Deviation) [T-score]	35.45 (12.33)	38.07 (10.45)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	MATRICS Consensus Cognitive Battery
Description	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.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Pramipexole	Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
Measure Participants	28	26
Mean (Standard Deviation) [T-score]	35.57 (13.87)	39.81 (11.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	t-test, 2 sided
	Comments

3. Primary Outcome

Title	MATRICS Consensus Cognitive Battery
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
Measure Participants	26	24
Mean (Standard Deviation) [T-score]	36.46 (13.61)	41.50 (11.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Young Mania Rating Scale (YMRS)
Description	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.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pramipexole	Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
Measure Participants	33	30
Mean (Standard Deviation) [score on a scale]	-0.92 (2.21)	-0.57 (1.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Hamilton Rating Scale for Depression (HRSD)
Description	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.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pramipexole	Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
Measure Participants	33	30
Mean (Standard Deviation) [score on a scale]	-0.24 (3.78)	-.22 (3.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Brief Psychiatric Rating Scale (BPRS)
Description	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.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Pramipexole	Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
Measure Participants	32	29
Mean (Standard Deviation) [score on a scale]	-0.63 (3.53)	-0.61 (3.70)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Number of Participants With Suicidal Acknowledgements
Description	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).
Time Frame	up to Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pramipexole	Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
Measure Participants	33	30
Count of Participants [Participants]	0 0%	5 16.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Tabulation of participants with suicidal acknowledgements over 12-week study

8. Secondary Outcome

Title	The Probabilistic Stimulus Selection Task
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pramipexole	Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
Measure Participants	18	21
Mean (Standard Deviation) [percentage of accuracy]	56.94 (17.00)	67.56 (20.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	t-test, 2 sided
	Comments

9. Secondary Outcome

Title	The Probabilistic Stimulus Selection Task
Description	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.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pramipexole	Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
Measure Participants	19	18
Mean (Standard Deviation) [percentage of accuracy]	56.91 (22.60)	56.94 (22.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1.00
	Comments
	Method	t-test, 2 sided
	Comments

10. Secondary Outcome

Title	The Probabilistic Stimulus Selection Task
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pramipexole	Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
Measure Participants	19	19
Mean (Standard Deviation) [percentage of accuracy]	59.54 (21.59)	50.99 (16.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
Arm/Group Title	Pramipexole		Placebo
Arm/Group 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. Pramipexole: Up to 4.5mg, PO, (by mouth) per day of the 12-week 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. Placebo: placebo match study drug
All Cause Mortality
	Pramipexole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/30 (0%)
Serious Adverse Events
	Pramipexole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Pramipexole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/33 (54.5%)		5/30 (16.7%)
Ear and labyrinth disorders
Ringing in Ears	1/33 (3%)	1	2/30 (6.7%)	2
Eye disorders
Blurred Vision	1/33 (3%)	1	1/30 (3.3%)	1
Gastrointestinal disorders
Nausea/Vomiting	2/33 (6.1%)	2	2/30 (6.7%)	2
General disorders
Headache	1/33 (3%)	1	0/30 (0%)	0
Poor Coordination	1/33 (3%)	1	0/30 (0%)	0
Dizziness	1/33 (3%)	1	0/30 (0%)	0
Difficulty Sleeping	1/33 (3%)	1	0/30 (0%)	0
Poor Concentration	2/33 (6.1%)	2	0/30 (0%)	0
General malaise	1/33 (3%)	1	0/30 (0%)	0
Fatigue	1/33 (3%)	1	0/30 (0%)	0
Decreased Energy	2/33 (6.1%)	2	0/30 (0%)	0
Psychiatric disorders
Anxiety	1/33 (3%)	1	0/30 (0%)	0
Renal and urinary disorders
Painful Urination	1/33 (3%)	1	0/30 (0%)	0
Reproductive system and breast disorders
Menstrual Irregularity	1/33 (3%)	1	0/30 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/33 (3%)	1	0/30 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.