Brexpiprazole for Bipolar Depression
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|ClinicalTrials.gov Identifier: NCT03427892|
Recruitment Status : Completed
First Posted : February 9, 2018
Results First Posted : March 13, 2019
Last Update Posted : March 13, 2019
|First Submitted Date ICMJE||December 28, 2016|
|First Posted Date ICMJE||February 9, 2018|
|Results First Submitted Date ICMJE||November 13, 2018|
|Results First Posted Date ICMJE||March 13, 2019|
|Last Update Posted Date||March 13, 2019|
|Actual Study Start Date ICMJE||March 1, 2017|
|Actual Primary Completion Date||March 15, 2018 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||The Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Baseline through week 8 ]
The Montgomery-Asberg Depression Rating Scale is used to assess depressive symptom severity. There are 10 items and each item is rated from 0 to 6 (increasing severity) based on the assessment of symptoms within the past 7 days. Scoring is assisted by descriptive anchors that serve as useful guides at 0,2,4, 8. Odd numbers (1,3,5) between the descriptive anchors are also meant to be scored. Highest possible MADRS score is 60. Lowest possible MADRS score is 0. MADRS is scored by taking the sum of the scores for each item. A higher score is indicative of more acute depressive symptoms.
|Original Primary Outcome Measures ICMJE
||The Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 8 weeks ]
The Montgomery-Asberg Depression Rating Scale is used to assess depressive symptom severity
|Change History||Complete list of historical versions of study NCT03427892 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures
||High Sensitivity C-Reactive Protein (Hs-CRP) [ Time Frame: Baseline and at week 8 ]
high sensitivity C-Reactive Protein values will be used to measure inflammation
|Original Other Pre-specified Outcome Measures
|Brief Title ICMJE||Brexpiprazole for Bipolar Depression|
|Official Title ICMJE||Brexpiprazole for Bipolar Depression|
The investigators will conduct an 8-week, non-randomized, open-label study of brexpiprazole in 20 persons with bipolar I or II disorder, depressed mood state. Primary aim will be to assess if brexpiprazole is associated with a reduction in depressive symptom severity using the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary aims will include an assessment of the following in patients with bipolar disorder taking brexpiprazole: manic symptoms, cognition, safety and tolerability of brexpiprazole, and quality of life.
Subjects will be discontinued from the study if any of the following conditions occurs: change in diagnosis to other than bipolar I or II disorder, development of active suicidal or homicidal ideation with plan and intent, worsening of mood symptoms, that in the opinion of the investigators requires discontinuation, pregnancy, development of severe life-threatening medical condition, involuntary psychiatric hospitalization or incarceration.
We will conduct an 8-week, non-randomized, open label study of brexpiprazole in 20 persons with bipolar disorder. Primary Aim will be to determine if brexpiprazole is associated with a reduction in depressive symptom severity using the Montgomery-Asberg Depression Rating Scale (MADRS) in outpatients with bipolar disorder, depressed mood state. Secondary Aims will be: 1) Assess manic symptoms in patients with bipolar disorder receiving brexpiprazole, 2) Assess cognition in patients with bipolar disorder receiving brexpiprazole, 3) Assess the safety and tolerability of brexpiprazole in patients with bipolar disorder, 4) Assess quality of life in patients with bipolar disorder receiving brexpiprazole. Subjects will be discontinued from the study if any of the following conditions occurs: change in diagnosis to other than bipolar I or II disorder, development of active suicidal or homicidal ideation with plan and intent, worsening in mood symptoms, that in the opinion of the investigators requires discontinuation, pregnancy, development of severe or life-threatening medical condition, involuntary psychiatric hospitalization or incarceration.
Baseline: This visit will be split into two portions: Baseline 1 and Baseline 2.
For Baseline 1 (~3 hours), the psychiatric diagnosis will be confirmed by the structured clinical interview for DSM-5 (SCID), mood assessed via the Montgomery-Asberg Depression Rating Scale (MADRS), depression via the Inventory of Depressive Symptomatology Self-Report (IDS-SR30), mania via the Young Mania Rating Scale, and quality of life via the Quality of Life in Bipolar Disorder (QOLBD). Blood will be drawn for complete blood count (CBC), Comprehensive Metabolic Panel (CMP, includes a liver panel with AST, ALT, as well as lipids), and high-sensitivity c-reactive protein (hs-CRP). A urine sample for drug screen and pregnancy test (if applicable), psychiatrist assessment, physical exam, collection of weight and vitals will be completed.
For Baseline 2 (~2 hours), recent depressive symptoms will be assessed via the IDS-SR30 and MADRS, mania via the YMRS, current mood via Internal State Scale (ISS), suicidal ideation will be assessed via the Columbia Suicide Severity Rating Scale (CSSRS), safety and side effects will be assessed with the SAFTEE, the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Scale (BAS) and Simpson-Angus Scale (SAS). Subjects will also complete the The Ray Auditory Verbal Learning Test (RAVLT) to assess word memory, the Stroop test to measure attention, speed, and accuracy of thinking, and The Trail Making Test (TMT) to measure attention, speed and accuracy. A urine sample for drug screen and pregnancy test (if applicable) will also be completed. Brexpiprazole capsules will be initiated at 0.5 mg/day.
Baseline 2 to Week 1: Subjects will be given the ISS to fill out at home. Subjects will be asked to complete the scale at home on 7 consecutive days between Baseline 2 and Week 1 visits and return the filled out scales to the researcher's office. The scale will take approximately 3-5 minutes to fill out.
Week 1, 2, 3, 6 (~1.5 hours each): Subjects will complete the MADRS, YMRS, IDS-SR30, ISS, SAFTEE, CSSRS, AIMS, BAS, SAS, and a urine sample will be collected for a drug screen. Subjects will meet with the psychiatrist for weekly assessment and vitals will be collected.
Week 4 (~2 hours): Subjects will complete the MADRS, IDS-SR, YMRS, SAFTEE, ISS, C-SSRS, AIMS, BAS, SAS, RAVLT, Stroop, TMT, vital signs, a urine sample for a drug screen and a urine pregnancy test, and visit the doctor for a psychiatric evaluation.
Week 8 (final visit ~2.5 hours): Subjects will complete the MADRS, IDS-SR, YMRS, SAFTEE, ISS, C-SSRS, AIMS, BAS, SAS, RAVLT, Stroop, TMT, QOLBD, vital signs, a urine sample for drug screen, take a urine pregnancy test, have blood drawn for clinical testing (CBC, CMP, hs-CRP), and visit the doctor for a psychiatric evaluation and physical exam. During this visit, participants will also be provided with aftercare referral information and will begin their medication taper. The medication taper schedule is described below under "Study Medication and Intervention Description".
Safety Phone Call (~15 min): Participants will receive a phone call from researchers 7-10 days following their Week 8 study visit (at the end of their tapering schedule). During this phone call, the researchers will assess any withdrawal effects or adverse events and check on the status of the aftercare referrals.
Participants will be paid for their time and inconvenience per visit as follows: $60 at Baseline 1, Baseline 2, weeks 1, 2, 3, 6; $70 at week 4; $90 for week 8. Participants will also be paid for each ISS scale they bring back at the rate of $1 per scale (maximum $7). These payments will be processed during Week 1 visit. These payments will be completed via the ClinCard system. Bus or rail passes will be provided. After study completion, standard psychiatric care will be provided until referral is arranged.
Study Medication and Intervention Description:
Participants will be initiated on a 0.5 mg/day brexpiprazole dose (week 0/baseline); after one week the dose will be increased to 1 mg/day (week 1), after another week to 2 mg/day (week 2). If any dose appears to be poorly tolerated, the dose titration can be slowed or stopped based on clinician judgment. If response in weeks 3-6, defined as a 50% reduction in the MADRS, has not been achieved, and the current dose is well tolerated, then additional dose increases to 3 mg/day and 4 mg/day (maximum allowed dose in protocol) will occur with at least a one week interval between dose increases.
Following the last study visit (Week 8), participants will be gradually tapered off the medication every 2 days until they stop taking the medication completely. For example, if a participants takes 4 mg of brexpiparzole at Week 8, then he/she will take 3 mg for 2 days, then 2 mg for 2 days, then 1 mg for 2 days, and then 0.5 mg for 2 days. At the end of the tapering period (7-10 days depending on the highest brexpiprazole dose at the end of the study), participants will receive a safety phone call from a research staff member to assess any withdrawal symptoms and check on the status of the aftercare referrals.
Primary Aim: Determine if brexpiprazole is associated with a reduction in depressive symptom severity in outpatients with bipolar disorder, depressed mood state.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 4|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||Bipolar Depression|
|Intervention ICMJE||Drug: Brexpiprazole
Brexpiprazole is an atypical antipsychotic drug that is used to treat mental/mood disorders.
Other Name: Rexulti
|Study Arms ICMJE||Experimental: Brexpiprazole
Brexipiprazole will be taken orally beginning at 0.5 mg/day with an increase to 1 mg/day at week 1 and 2 mg/day at week 2. If reduction in mood symptoms does not occur, the dose will increase to 3 mg/day and 4 mg/day.
Intervention: Drug: Brexpiprazole
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Actual Study Completion Date ICMJE||March 15, 2018|
|Actual Primary Completion Date||March 15, 2018 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years to 65 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT03427892|
|Other Study ID Numbers ICMJE||102016-048|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||
|Responsible Party||University of Texas Southwestern Medical Center|
|Study Sponsor ICMJE||University of Texas Southwestern Medical Center|
|Collaborators ICMJE||Otsuka America Pharmaceutical|
|PRS Account||University of Texas Southwestern Medical Center|
|Verification Date||March 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP