Study of the Efficacy of Lurasidone in Cognitive Functioning in Bipolar Patients

Bipolar Disorder Clinical Trial

— ELICE_BD  

Official title:

A 6-Week Randomised, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy of Lurasidone Adjunctive Therapy in Improving Cognitive Functioning in Euthymic Bipolar Disorder Patients (ELICE-BD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02731612
• Other study ID #: H16-00129
• Status: Recruiting
• Phase: Phase 3
• Start date: May 8, 2017
• Est. completion date: March 31, 2025

Study information

• Verified date: November 2023
• Source: University of British Columbia
• Contact: Nazlin Walji, B.Sc
• Phone: 604-822-7294
• Email: nazlin.walji[@]ubc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, placebo-controlled, multicentre, parallel-group study to assess the cognitive effects of lurasidone in bipolar I and II patients (manic depression) who are in remission from an episode. Participants who show cognitive impairment at the screening visit will be enrolled into the study and randomized at the baseline visit to receive either lurasidone or placebo adjunctive therapy in a 1:1 ratio for 6 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: March 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Males or females aged 19 to 65 years inclusive.

2. Diagnostic and Statistical Manual of Mental Disorder, 5th Edition (DSM.5) diagnosis of Bipolar Type I or Type II Disorder, with or without a history of psychosis. BP II patients must have had 2 definite periods of hypomania in the last 5 years.

3. All patients must be taking either a mood stabilizer (i.e. lithium or valproate) (lamotrigine as a mood stabilizer is acceptable for bipolar 2 disorder patients only and not for bipolar I disorder) 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 atypical antipsychotics are excluded. Combinations of these medications as outlined above, or the combination of any of them with lamotrigine 100-400 mg daily, or the combination of a mood stabilizer plus asenapine 5-20 mg/day, are also permitted.

4. All concomitant medication must be at a stable dose for two weeks prior to the randomization visit.

5. Clinically stable during the last 4 weeks as assessed by clinical interview.

6. A Montgomery Asberg Depression Rating Scale(MADRS) and Young Mania Rating Scale (YMRS) score less than or equal to 8.

7. Patients who show cognitive impairments (-0.50 SD or below) on either the Wechsler Adult Intelligence Scale-IV (WAIS-IV) -Coding subtest, or the Rey Auditory Verbal Learning Test (RAVLT) total learning score on trials 1 to 5 or immediate recall, at screening visit.

8. A WAIS-IV vocabulary scaled score >5 (equivalent to estimated IQ 80 or greater).

9. A sufficient level of the English or Japanese language.

10. Females who are postmenopausal for at least 1 year before the screening visit (confirmed by an FSH test) or are surgically sterile.

11. Females of childbearing potential who are taking contraceptive pills or agree to practice 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 dosing stops, or who agree to completely abstain from heterosexual intercourse.

12. 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.

Exclusion Criteria:

1. 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.

2. Patients taking procognitive medications, clozapine, tricyclic antidepressants, first-generation antipsychotics, and cogentin.

3. Those taking two or more antipsychotics.

4. Those taking strong CYP3A4 inhibitors (e.g. clarithromycin, nefazodone, grapefruit juice) or strong CYP3A4 inducers (e.g. carbamazepine, St John's wort (Hypericum perforatum). Please refer to the current Lurasidone SmPC for further listed contraindications.

5. Anticholinergics and stimulants that increase dopamine levels are not permitted

6. Cognitive remediation therapy within 3 months prior to entry or during the double blind phase.

7. Neuromodulation treatment with ECT or rTMS or tDCS or DBS within eight weeks or treatment with an experimental drug within 30 days.

8. History of nonresponse or intolerance to lurasidone.

9. Psychotic disorder other than Bipolar Disorder.

10. Patients who currently meet criteria for anxiety disorder (GAD, OCD, Panic disorder, PTSD).

11. Those with a current or lifetime diagnosis of ADHD or other learning disorders.

12. Axis I diagnosis of alcohol/substance abuse or dependence within the past month.

13. Significant risk of harm to self or others.

14. Pregnancy or lactation.

15. Liver function tests (AST and ALT) three times the upper limit of normal.

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• lurasidone
Atypical Antipsychotic

Other:
• Placebo
Inactive substance

Locations

Country	Name	City	State
Canada	UBC Mood Disorders Center	Vancouver	British Columbia
Japan	Department of Psychiatry, Fujita Health University School of Medicine	Aichi	Toyoake
Japan	Department of Psychiatry, Hokkaido University Graduate School of Medicine	Kita-ku	Sapporo
Japan	Department of Psychiatry, University of Occupational and Environmental Health	Kitakyushu	Fukuoka
Japan	National Center of Neurology and Psychiatry	Kodaira	Tokyo
Japan	Department of Neuropsychiatry, Kansai Medical University	Moriguchi-shi	Osaka
United Kingdom	Institute of Psychiatry, Psychology and Neuroscience,King's College London	London	England
United States	The Brigham and Women's Hospital, Department of Psychiatry	Boston	Massachusetts
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Nazlin Walji

Countries where clinical trial is conducted

United States,  Canada,  Japan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in cognitive performance in Euthymic bipolar patients treated with Lurasidone vs Placebo adjunctive therapy.	Cognitive improvement will be measured by changes in composite cognitive score from baseline to endpoint, extracted from the International Society for Bipolar Disorders-Battery for Assessment of Neurocognition.	6 weeks
Secondary	Change in Depression	Montgomery Asberg Depression Rating Scale (MADRS) will be used to assess changes in bipolar depression from baseline to endpoint.	6 weeks
Secondary	Change in Mania	The Young Mania Rating Scale (YMRS) will be used to assess changes in mania from baseline to endpoint.	6 weeks
Secondary	Improvement in overall psychiatric status	Clinical Global Improvement Scale will be used to assess change from baseline to endpoint in overall psychiatric status.	6 weeks
Secondary	Improvement in Quality of Life	Quality of Life, Bipolar Version Scale will be used to assess improvement in quality of life from baseline to endpoint.	6 weeks
Secondary	Improvement in Subjective-rated Cognitive Functioning	Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) will be used to assess changes in subjective cognitive functioning from baseline to endpoint.	6 weeks
Secondary	Improvement in Objectively Rated Daily Functioning	Functioning Assessment Short Test (FAST) will be used to assess improvement in objectively rated daily functioning, defined as change in scores from baseline to endpoint.	6 weeks
Secondary	Improvement in Subjectively Rated Daily Functioning	Sheehan Disability Scale (SDS) will be used to assess improvement in subjectively rated daily functioning, defined as change in scores from baseline to endpoint.	6 weeks