Assessing the Role of Cariprazine in Improving Cognition in Euthymic Bipolar Patients

NCT04771299 | Terminated Phase 3 DMC

• 1 other identifier: H20-01293
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Some patients with bipolar disorder show broad cognitive impairments (e.g. difficulty with concentration, problem solving, memory etc.) that persist during euthymia (no symptoms of depression or mania) despite remission of mood symptoms. Cognitive deficits (significant cognitive impairments) in bipolar disorder are associated with impairments in everyday functioning and quality of life. Thus, improving cognitive functioning is an important treatment goal in people with bipolar disorder. In a recent study, investigators have demonstrated that lurasidone; an atypical antipsychotic was more effective than treatment as usual in improving cognition. The study will examine the efficacy of Cariprazine (VRAYLAR®) in improving cognition in patients with bipolar disorder. Cariprazine is a novel atypical antipsychotic medication that has been approved by the Food and Drug Administration (FDA) for treatment of schizophrenia, manic or mixed, and depressive episodes associated with bipolar I disorder. This study is a randomized (like the flip of a coin), double-blind (participant and the study team will not know which treatment arm participant will receive) study in which 30 participants will be randomized across two sites in Canada.

Conditions

Bipolar I Disorder; Cognitive Impairment

Keywords

Bipolar I Disorder; Euthymia; Cariprazine; Cognition; Memory

Outcome Measures

Primary Outcomes (2)

• Improvement in cognitive performance

  The primary efficacy measure will be improvement in cognitive performance, as measured by changes in composite cognitive score from baseline to endpoint, extracted from the International Society for Bipolar Disorders-Battery for Assessment of Neurocognition. The higher the scores the better the outcome.

  6 weeks

• Improvement in functioning

  The co-primary efficacy measure will include changes in functioning from baseline to endpoint measured using UCSD based performance skills assessment-brief version. The higher the scores the better the outcome.

  6 weeks

Secondary Outcomes (7)

• Change in depression

  6 weeks

• Change in Mania

  6 weeks

• Improvement in overall psychiatric status

  6 weeks

• Improvement in Quality of Life

  6 weeks

• Improvement in Subjective-rated Cognitive Functioning

  6 weeks

Study Arms (2)

Cariprazine

ACTIVE COMPARATOR

1.5mg of Cariprazine added to their current treatment for 6 week period

Drug: Cariprazine

Placebo

PLACEBO COMPARATOR

Matching placebo added to their current treatment for 6 week period.

Other: Placebo

Interventions

Cariprazine DRUG

Cariprazine is a novel atypical antipsychotic medication that has been approved by the Food and Drug Administration (FDA) for treatment of schizophrenia, manic or mixed, and depressive episodes associated with bipolar I disorder.

Also known as: VRAYLAR®

Cariprazine

Placebo OTHER

Placebo is an inactive substance that looks identical to the study medication that contains no therapeutic ingredient.

Placebo

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged 19 to 65 years inclusive.
• DSM-5 diagnosis of Bipolar I Disorder, with or without a history of psychosis.
• All patients must be taking either a mood stabilizer (i.e. lithium or valproate) or an atypical antipsychotic, or a combination of these (two mood stabilizers or a mood stabilizer plus an atypical antipsychotic), at therapeutic doses, for mood stabilization. Those taking two or more atypical antipsychotics are excluded. Medications and therapeutic doses are: lithium, serum level 0.6-1.2 mEq/L; divalproex/sodium valproate, serum level 350-700 mM/L (45-125 mcg/ml); risperidone 1-6 mg/day; olanzapine 5-20 mg/day; quetiapine IR or XR 300-800 mg/day; aripiprazole 10-30 mg/day; asenapine 5-20 mg/day, or ziprasidone 80-160 mg/day.
• All concomitant medication must be at a stable dose for a minimum of two weeks prior to randomization.
• Clinically stable during the last 4 weeks, as assessed by clinical interview, prior to the randomization visit.
• A MADRS and YMRS score less than or equal to 8.
• Patients who show cognitive impairments, defined as 0.5 standard deviations below the mean or worse (Z = -0.5 or lower), on either the WAIS-IV Coding subtest, or the RAVLT total learning score on trials 1-5 or immediate recall trial, at screening visit.
• A WAIS-IV vocabulary scaled score ≥ 5 (equivalent to estimated IQ 80 or greater).
• A sufficient level of English language.
• Females who are postmenopausal for at least 1 year before the screening visit (confirmed by an FSH test) or are surgically sterile.
• Females of childbearing potential who are taking contraceptive pills or agree to practice highly effective double barrier methods of contraception, from the time of signing the informed consent up to the last dose of study drug, and for 7 days after the last dose. Abstinence will only be considered an adequate form of contraception if it is the usual and preferred method.
• Capability of understanding, consenting to, and complying with study requirements, study visits, and to return to the clinic for follow-up evaluations as specified by the protocol.

You may not qualify if:

• A history of unstable or inadequately treated medical illnesses including moderate to severe brain injury, or neurological illnesses impacting cognitive function. Patients with a personal or family history of cardiac problems will need to undergo EKG at screen visit, and will be excluded if results are abnormal.
• Participants taking procognitive medications, clozapine, tricyclic antidepressants, first-generation antipsychotics, benztropine, cogentin or lurasidone at screening visit.
• Those taking two or more antipsychotics.
• Anticholinergics and stimulants that increase dopamine levels are not permitted.
• Cognitive remediation therapy within 3 months prior to entry or during the double blind phase.
• Neuromodulation treatment with ECT or DBS within 8 weeks, or rTMS, tDCS or experimental drug treatment within 30days.
• History of nonresponse or intolerance to cariprazine.
• Psychiatric disorder other than bipolar disorder.
• Participants who currently meet criteria for anxiety disorder (GAD, OCD, panic disorder, PTSD).
• Those with a current or lifetime diagnosis of ADHD or other learning disorders.
• Those meeting DSM-5 criteria for alcohol or substance abuse or dependence disorder within the past month.
• Significant risk of harm to self or others.
• Those with severe personality disorders causing significant impairment in functioning.
• Pregnancy or lactation.
• Liver function tests (AST and ALT) three times the upper limit of normal.

Sponsors & Collaborators

• Lakshmi N Yatham: lead

Study Sites (1)

Djavad Mowfaghian Centre for Brain Heath

Vancouver, British Columbia, V6T 1Z3, Canada

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

cariprazine

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Lakshmi N Yatham, MBBS,MRCPsyc

  University of British Columbia, Department of Psychiatry, BC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: February 25, 2021
• Study Start: July 7, 2021
• Primary Completion: September 8, 2024
• Study Completion: September 8, 2024
• Last Updated: October 26, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)