Bipolar DisorderPhase 4PRAM-BDNCT02397837
Targeting Cognition in Bipolar Disorder With Pramipexole
A Phase 4 study testing Pramipexole in people with Bipolar Disorder, run by Brigham and Women's Hospital at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Pramipexole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- 3 sitesUnited States
- Study dates
- Oct 2014to 26 Jul 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
The Zucker Hillside Hospital
Glen Oaks, New York, 11004
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Pramipexole in Bipolar Disorder: Targeting Cognition (PRAM-BD)
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.
Read the 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).
- Conditions
- Bipolar Disorder
- Being tested
- Pramipexole, Placebo
- Keywords
- Bipolar Disorder, Cognition
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PramipexoleDrug
Also called Mirapex
Up to 4.5mg, PO, (by mouth) per day of the 12-week study.
PlaceboDrug
placebo match study drug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pramipexole |
| 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Week 12
Secondary outcomes (7)
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.
Measured: Baseline and week 12
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2015 (estimated)
- Study startOct 2014
- Primary completion26 Jul 2018
- Study completion26 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Zucker Hillside Hospital, Northwell Health, National Institute of Mental Health (NIMH), Icahn School of Medicine at Mount Sinai
- Responsible party
- Principal investigator, Katherine Burdick, Brigham and Women's Hospital
- Investigators
- Katherine Burdick, PhD, Principal investigator, Icahn School of Medicine at Mount SinaiAnil Malhotra, MD, Principal investigator, The Zucker Hillside Hospital, North Shore LIJ- Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02397837
- Sponsor's protocol ID
- 2017P001185
- Other IDs
- 1R01MH102257, 1R01MH102309
- Acronym
- PRAM-BD
- Status last verified
- Feb 2020
- First submitted
- 19 Mar 2015
- Last updated
- 28 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 22152405Goldberg 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.
PubMed 14992985
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pramipexole in Bipolar Disorder: Targeting Cognition (PRAM-BD)
- ClinicalTrials.gov ID
- NCT02397837
- Acronym / sponsor ID
- PRAM-BD / 2017P001185
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar Disorder, Cognition
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- The Zucker Hillside Hospital, Northwell Health, National Institute of Mental Health (NIMH), Icahn School of Medicine at Mount Sinai
- Study start
- Oct 2014
- Primary completion
- 26 Jul 2018 (actual)
- Study completion
- 26 Jul 2018 (actual)
- First posted
- 25 Mar 2015 (estimated)
- Results
- Posted 28 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pramipexole | Experimental | Drug: PramipexolePramipexole, 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 | Drug: PlaceboPlacebo, 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PramipexoleAlso: MirapexUp to 4.5mg, PO, (by mouth) per day of the 12-week study. | Drug | Pramipexole |
| Placeboplacebo match study drug | Drug | Placebo |
Primary outcome
MATRICS Consensus Cognitive Battery
Time frame: 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.
MATRICS Consensus Cognitive Battery
Time frame: 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.
MATRICS Consensus Cognitive Battery
Time frame: 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.
7 secondary outcomes
Young Mania Rating Scale (YMRS)
Time frame: Baseline and week 12
Hamilton Rating Scale for Depression (HRSD)
Time frame: Baseline and week 12
Brief Psychiatric Rating Scale (BPRS)
Time frame: Baseline and week 12
Number of Participants With Suicidal Acknowledgements
Time frame: up to Week 12
The Probabilistic Stimulus Selection Task
Time frame: Baseline
The Probabilistic Stimulus Selection Task
Time frame: Week 6
The Probabilistic Stimulus Selection Task
Time frame: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22152405Burdick 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.
- Background: PubMed 14992985Goldberg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine Burdick, PhD principal investigator
Icahn School of Medicine at Mount Sinai
Anil Malhotra, MD principal investigator
The Zucker Hillside Hospital, North Shore LIJ- Health System
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pramipexole in people with Bipolar Disorder, run by Brigham and Women's Hospital at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MATRICS Consensus Cognitive Battery (time frame: Baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02397837, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2020.