Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1R01MH102257 | U.S. NIH Grant/Contract | View source | |
| 1R01MH102309 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| The Zucker Hillside Hospital | OTHER |
| Northwell Health | OTHER |
| National Institute of Mental Health (NIMH) | NIH |
| Icahn School of Medicine at Mount Sinai |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pramipexole | Experimental | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pramipexole | Drug | Up to 4.5mg, PO, (by mouth) per day of the 12-week study. |
|
| Measure | Description | Time Frame |
|---|---|---|
| MATRICS Consensus Cognitive Battery | 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. | Baseline |
| MATRICS Consensus Cognitive Battery | 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. | Week 6 |
| MATRICS Consensus Cognitive Battery | 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. | Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Young Mania Rating Scale (YMRS) | 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. | Baseline and week 12 |
Not provided
Inclusion criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Katherine Burdick, PhD | Icahn School of Medicine at Mount Sinai | Principal Investigator |
| Anil Malhotra, MD | The Zucker Hillside Hospital, North Shore LIJ- Health System | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States | ||
| The Zucker Hillside Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22152405 | Background | 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. | |
| 14992985 | Background | 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. doi: 10.1176/appi.ajp.161.3.564. |
Not provided
Not provided
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).
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | MATRICS Consensus Cognitive Battery | 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. | Posted | Mean | Standard Deviation | T-score | Baseline |
|
Adverse event data collected from time of randomization/baseline visit through week 12 visit (end of study).
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea/Vomiting | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Katherine Burdick | Brigham and Women's Hospital | 617-732-5789 | kburdick1@bwh.harvard.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Zucker Hillside Hospital Site | Oct 23, 2017 | Jul 25, 2019 | Prot_SAP_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Brigham and Women's Hospital Site | Aug 29, 2018 | Jul 25, 2019 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Sep 6, 2018 | Jul 25, 2019 | ICF_002.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Mount Sinai School of Medicine Site | May 6, 2017 | Jan 13, 2020 | Prot_SAP_003.pdf |
Not provided
| ID | Term |
|---|---|
| D001714 | Bipolar Disorder |
| ID | Term |
|---|---|
| D000068105 | Bipolar and Related Disorders |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077487 | Pramipexole |
| ID | Term |
|---|---|
| D052160 | Benzothiazoles |
| D013844 | Thiazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided
| OTHER |
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | placebo match study drug |
|
| Hamilton Rating Scale for Depression (HRSD) |
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. |
| Baseline and week 12 |
| Brief Psychiatric Rating Scale (BPRS) | 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. | Baseline and week 12 |
| Number of Participants With Suicidal Acknowledgements | 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). | up to Week 12 |
| The Probabilistic Stimulus Selection 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. | Baseline |
| The Probabilistic Stimulus Selection 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. | Week 6 |
| The Probabilistic Stimulus Selection 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. | Week 12 |
| Glen Oaks |
| New York |
| 11004 |
| United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| 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 |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | 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 |
|
|
|
| Primary | MATRICS Consensus Cognitive Battery | 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. | 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. | Posted | Mean | Standard Deviation | T-score | Week 6 |
|
|
|
|
| Primary | MATRICS Consensus Cognitive Battery | 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. | Posted | Mean | Standard Deviation | T-score | Week 12 |
|
|
|
|
| Secondary | Young Mania Rating Scale (YMRS) | 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. | Average change in YMRS based on baseline and week 12 score. | Posted | Mean | Standard Deviation | score on a scale | Baseline and week 12 |
|
|
|
|
| Secondary | Hamilton Rating Scale for Depression (HRSD) | 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. | Average change in HRSD based on baseline and week 12 score. | Posted | Mean | Standard Deviation | score on a scale | Baseline and week 12 |
|
|
|
|
| Secondary | Brief Psychiatric Rating Scale (BPRS) | 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline and week 12 |
|
|
|
|
| Secondary | Number of Participants With Suicidal Acknowledgements | 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). | Posted | Count of Participants | Participants | up to Week 12 |
|
|
|
|
| Secondary | The Probabilistic Stimulus Selection 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. | The discrepancy in participants analyzed from participants in Participant Flow is due to availability of data because of software issues in running task. | Posted | Mean | Standard Deviation | percentage of accuracy | Baseline |
|
|
|
|
| Secondary | The Probabilistic Stimulus Selection 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. | The discrepancy in participants analyzed from participants in Participant Flow is due to availability of data because of software issues in running task. | Posted | Mean | Standard Deviation | percentage of accuracy | Week 6 |
|
|
|
|
| Secondary | The Probabilistic Stimulus Selection 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. | The discrepancy in participants analyzed from participants in Participant Flow is due to availability of data because of software issues in running task. | Posted | Mean | Standard Deviation | percentage of accuracy | Week 12 |
|
|
|
|
| 0 |
| 33 |
| 0 |
| 33 |
| 18 |
| 33 |
| EG001 | 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 | 0 | 30 | 0 | 30 | 5 | 30 |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Headache | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Poor Coordination | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Dizziness | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Blurred Vision | Eye disorders | MedDRA (10.0) | Systematic Assessment |
|
| Ringing in Ears | Ear and labyrinth disorders | MedDRA (10.0) | Systematic Assessment |
|
| Painful Urination | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
|
| Menstrual Irregularity | Reproductive system and breast disorders | MedDRA (10.0) | Systematic Assessment |
|
| Difficulty Sleeping | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Poor Concentration | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| General malaise | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (10.0) | Systematic Assessment |
|
| Decreased Energy | General disorders | MedDRA (10.0) | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D006571 |
| Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |