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Brexpiprazole Treatment for Bipolar I Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04569448
Recruitment Status : Not yet recruiting
First Posted : September 29, 2020
Last Update Posted : October 8, 2020
Sponsor:
Collaborators:
McMaster University
Jewish General Hospital
Information provided by (Responsible Party):
Serge Beaulieu, Douglas Mental Health University Institute

Brief Summary:
Bipolar disorder (BD) is a frequent and lifelong recurrent mood disorder with treatment-resistant depressive episodes. Importantly, depressive symptoms and cognitive decline are major determinants of functionality and quality of life in this clinical population. There is robust evidence that individuals with BD have neurocognitive deficits (especially in memory and executive functioning domains) compared to the healthy population. These deficits are present in all mood states and can greatly affect patients' functional capacity, often more so than mood symptoms themselves. Many pharmacological treatments for BD adversely affect cognition, and those that are beneficial can be difficult to use. There is thus a pressing need to identify a safe, easy-to-use medication that can target both cognitive deficits and depressive symptoms in BD. It is expected that Brexpiprazole adjunctive treatment will be efficacious in treating BD type I depression by improving mood symptoms, as well as cognitive capacity and global functioning, and that such changes will be accompanied by concurrent alterations in associated brain structures.

Condition or disease Intervention/treatment Phase
Bipolar Depression Drug: Brexpiprazole Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Low-Dose Adjunctive Brexpiprazole in the Treatment of Bipolar I Depression: An Open-Label Pilot Study
Estimated Study Start Date : November 2020
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Patient
Individuals diagnosed with Bipolar Disorder Type I and suffering a major depressive episode who will receive an adjunctive and variable dose of Brexpiprazole treatment
Drug: Brexpiprazole
Adjunctive variable dose (1-3 mg/day) Brexpiprazole




Primary Outcome Measures :
  1. Change from Baseline Depressive Symptoms as Assessed by MADRS at 8 weeks [ Time Frame: 8 weeks ]
    Percentage of response to treatment, as defined by a 50% improvement of depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) at 8 weeks. The overall MADRS score ranges from 0 to 60, where a higher score indicates more severe depression.


Secondary Outcome Measures :
  1. Change from Baseline Global Functioning as Assessed by FAST at 8 weeks [ Time Frame: 8 weeks ]
    Differential scores from baseline on Functioning Assessment Short Test (FAST) after 8 weeks of treatment. The overall FAST score ranges from 0 to 72, where a higher score indicates more severe difficulties.

  2. Change from Baseline Global Functioning as Assessed by FAST at 12 weeks [ Time Frame: 12 weeks ]
    Differential scores from baseline on Functioning Assessment Short Test (FAST) after 12 weeks of treatment. The overall FAST score ranges from 0 to 72, where a higher score indicates more severe difficulties.

  3. Change from Baseline Global Functioning as Assessed by FAST at 6 months [ Time Frame: 6 months ]
    Differential scores from baseline on Functioning Assessment Short Test (FAST) after 6 months of treatment. The overall FAST score ranges from 0 to 72, where a higher score indicates more severe difficulties.

  4. Change from Baseline Global Functioning as Assessed by CPFQ at 8 weeks [ Time Frame: 8 weeks ]
    Differential scores from baseline on Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) after 8 weeks. The overall CPFQ score ranges from 0 to 42, where a higher score indicates poorer functioning.

  5. Change from Baseline Global Functioning as Assessed by CPFQ at 12 weeks [ Time Frame: 12 weeks ]
    Differential scores from baseline on Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) after 12 weeks. The overall CPFQ score ranges from 0 to 42, where a higher score indicates poorer functioning.

  6. Change from Baseline Global Functioning as Assessed by CPFQ at 6 months [ Time Frame: 6 months ]
    Differential scores from baseline on Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) after 6 months.The overall CPFQ score ranges from 0 to 42, where a higher score indicates poorer functioning.

  7. Change from Baseline Global Functioning as Assessed by SDS at 8 weeks [ Time Frame: 8 weeks ]
    Differential scores from baseline on Sheehan Disability Scale (SDS) after 8 weeks. The overall SDS score ranges from 0 to 30, where a higher score indicates greater impairment.

  8. Change from Baseline Global Functioning as Assessed by SDS at 12 weeks [ Time Frame: 12 weeks ]
    Differential scores from baseline on Sheehan Disability Scale (SDS) after 12 weeks. The overall SDS score ranges from 0 to 30, where a higher score indicates greater impairment.

  9. Change from Baseline Global Functioning as Assessed by SDS at 6 months [ Time Frame: 6 months ]
    Differential scores from baseline on Sheehan Disability Scale (SDS) after 6 months. The overall SDS score ranges from 0 to 30, where a higher score indicates greater impairment.

  10. Number of Participants with Treatment-Related Adverse Events or Serious Adverse Events [ Time Frame: Up to 6 months ]
    Number of safety events as measured by adverse event (AE) and serious adverse event (SAE) reporting.

  11. Change from Baseline Impairments as Assessed by AIMS at 8 weeks [ Time Frame: 8 weeks ]
    Differential scores from baseline on Abnormal Involuntary Movement Scale (AIMS) at 8 weeks. The overall scores ranges from 0 to 12, where a higher score indicates greater impairment.

  12. Change from Baseline Impairments as Assessed by BARS at 8 weeks [ Time Frame: 8 weeks ]
    Differential scores from baseline impairments on Barnes-Akathisia Rating Scale (BARS) at 8 weeks. The overall score ranges from 0 to 9, where a higher score indicates greater severity.

  13. Switch Rate into Hypomania as Assessed by the YMRS at 8 weeks [ Time Frame: 8 weeks ]
    Percentage of switch into hypomania as defined by a Young Mania Rating Scale (YMRS) score ≥ 8 at 8 weeks.

  14. Switch Rate into Hypomania as Assessed by the YMRS at 12 weeks [ Time Frame: 12 weeks ]
    Percentage of switch into hypomania as defined by a Young Mania Rating Scale (YMRS) score ≥ 8 at 12 weeks.

  15. Change from Baseline Impairments as Assessed by CGI-I at 8 weeks [ Time Frame: 8 weeks ]
    Differential scores from baseline impairments on Clinical Global Impression-Improvement (CGI-I) at 8 weeks. Scores range from 0 to 7, where a higher score indicates worsening of the illness.

  16. Change from Baseline Impairments as Assessed by CGI-I at 12 weeks [ Time Frame: 12 weeks ]
    Differential scores from baseline impairments on Clinical Global Impression-Improvement (CGI-I) at 12 weeks. Scores range from 0 to 7, where a higher score indicates worsening of the illness.

  17. Change from Baseline Level of CRP at 8 weeks [ Time Frame: 8 weeks ]
    Differential baseline levels of C-reactive protein (CRP) (mg/L) at 8 weeks.

  18. Change from Baseline Level of CRP at 12 weeks [ Time Frame: 12 weeks ]
    Differential baseline levels of C-reactive protein (CRP) (mg/L) at 12 weeks.

  19. Change from Baseline Rest/Activity Rhythm at 8 weeks [ Time Frame: 8 weeks ]
    Differential baseline rest-activity rhythm regularity at 8 weeks as measured by standard deviation of sleep onset, midpoint of sleep, and sleep consolidation.

  20. Change from Baseline Cognition as Assessed by the SCIP at 8 weeks [ Time Frame: 8 weeks ]
    Differential scores from baseline cognitive impairments assessed using the Screen for Cognitive Impairment in Psychiatry (SCIP) at 8 weeks. Total scores range from 0 to 94, where higher scores indicate higher performance.

  21. Change from Baseline Cognition as Assessed by the SCIP at 12 weeks [ Time Frame: 12 weeks ]
    Differential scores from baseline cognitive impairments assessed using the Screen for Cognitive Impairment in Psychiatry (SCIP) at 12 weeks. Total scores range from 0 to 94, where higher scores indicate higher performance.

  22. Change from Baseline Cognition as Assessed by the SCIP at 6 months [ Time Frame: 6 months ]
    Differential scores from baseline cognitive impairments assessed using the Screen for Cognitive Impairment in Psychiatry (SCIP) at 6 months. Total scores range from 0 to 94, where higher scores indicate higher performance.

  23. Change from Baseline Hippocampal Volume as Assessed with MRI at 6 months [ Time Frame: 6 months ]
    Differential hippocampal volumes between baseline and 6 months as assessed with structural magnetic resonance imaging (MRI).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age: 18-75
  • Male or female
  • Bipolar Disorder type I
  • Current treatment-resistant depressive episode (with MADRS >/= 24 and item 2 (reported sadness) >/= 3) for a minimum of 2 weeks but </= 52 weeks at screening visit and baseline visit
  • Patients must have failed at least one other treatment for the current depressive episode
  • If female and of childbearing potential, is using an adequate method of contraception. Adequate methods of contraception include abstinence; oral contraceptive pill or surgically implanted device; intra-uterine device; condom plus spermicidal foam or jelly; or tubal ligation
  • Is treated with a mood stabilizer (lithium and/or valproate and/or lamotrigine and/or quetiapine </= 100mg/day)
  • Patient is able to give his(her) consent

Exclusion Criteria:

  • Is at high risk of suicide as defined by a score of >/= 3 to item 10 of MADRS and/or in the clinical opinion of the investigator
  • Hypo(mania) episode with YMRS >/= 8
  • Psychotic symptoms as defined by a score of >/= 4 to item 8 (content) of YMRS and/or in the opinion of the investigator
  • Is treated with fluoxetine OR carbamazepine
  • Is treated with risperidone OR olanzapine OR quetiapine > 100mg/day OR ziprazidone OR any other antipsychotic
  • Is pregnant or lactating or absence of contraceptive treatment
  • Drug abuse or dependence as per DSM-V (MINI)
  • Unstable medical condition
  • Other psychiatric condition, organic brain disorder, unstable and/or untreated medical condition such as hypothyroidism, hyperthyroidism, diabetes, cardiac condition, hypertension
  • Deficit in vitamin B12 or folate
  • Alcohol or drug abuse
  • Rapid cycling (more than 4 mood episodes per year)
  • Active or history of difficulty to swallow
  • Seizures not currently controlled with medications
  • Orthostatic hypotension
  • A history of clinically significant cardiovascular disorders and cardiac arrhythmias
  • A low white blood cell count
  • Known eye disease
  • Involuntary, irregular muscle movements, especially in the face
  • Known hypersensitivity to Brexpiprazole and any components of its formulation
  • Known lactose intolerance or have hereditary galactose intolerance or glucose-galactose malabsorption, because Brexpiprazole and placebo tablets contain lactose (a disaccharide of glucose and galactose)
  • Active inflammatory disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04569448


Contacts
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Contact: Gabriella Buck, MSc 514 444 5397 gabriella.buck@douglas.mcgill.ca
Contact: Paola Lavin Gonzalez, MD, MSc 438 389 8181 maria.lavingonzalez@mail.mcgill.ca

Locations
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Canada, Ontario
McMaster University
Hamilton, Ontario, Canada, L8S 4L8
Principal Investigator: Benicio Frey, MD, MSc, PhD         
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Principal Investigator: Soham Rej, MD, MSc         
Douglas Mental Health University Institute
Montreal, Quebec, Canada, H4H 1R3
Contact: Gabriella Buck, MSc    514 444 5397    gabriella.buck@douglas.mcgill.ca   
Contact: Paola Lavin Gonzalez, MD, MSc    438 389 8181    maria.lavingonzalez@mail.mcgill.ca   
Principal Investigator: Serge Beaulieu, MD, PhD, FRCPC, DFAPA         
Sponsors and Collaborators
Douglas Mental Health University Institute
McMaster University
Jewish General Hospital
Investigators
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Principal Investigator: Serge Beaulieu, MD, PhD, FRCPC, DFAPA Douglas Mental Health University Institute
Publications:

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Responsible Party: Serge Beaulieu, MD, PhD, FRCPC, DFAPA, Medical Chief, Douglas Mental Health University Institute
ClinicalTrials.gov Identifier: NCT04569448    
Other Study ID Numbers: RSS 5182913
First Posted: September 29, 2020    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Serge Beaulieu, Douglas Mental Health University Institute:
Brexpiprazole
Treatment-resistant depression
Cognition
Functioning
Rest-Activity rhythm
Hippocampus
CRP
Additional relevant MeSH terms:
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Depression
Depressive Disorder
Bipolar Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Bipolar and Related Disorders
Brexpiprazole
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Dopamine Agonists
Dopamine Agents