Clinical trial NCT02731612: Study of the Efficacy of Lurasidone in Cognitive Functioning in Bipolar Patients
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder
Keywords: Bipolar Disorder
Cognition
Euthymic
Lurasidone
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2016-04-07
Enrollment: 100
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Improvement in cognitive performance in Euthymic bipolar patients treated with Lurasidone vs Placebo adjunctive therapy.
timeFrame: 6 weeks
Secondary outcomes:
measure: Change in Depression
timeFrame: 6 weeks
measure: Change in Mania
timeFrame: 6 weeks
measure: Improvement in overall psychiatric status
timeFrame: 6 weeks
measure: Improvement in Quality of Life
timeFrame: 6 weeks
measure: Improvement in Subjective-rated Cognitive Functioning
timeFrame: 6 weeks
measure: Improvement in Objectively Rated Daily Functioning
timeFrame: 6 weeks
measure: Improvement in Subjectively Rated Daily Functioning
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: The Brigham and Women's Hospital, Department of Psychiatry
state: Massachusetts
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Vancouver
country: Canada
facility: UBC Mood Disorders Center
state: British Columbia
city: Kitakyushu
country: Japan
facility: Department of Psychiatry, University of Occupational and Environmental Health
state: Fukuoka
city: Moriguchi-shi
country: Japan
facility: Department of Neuropsychiatry, Kansai Medical University
state: Osaka
city: Kita-ku
country: Japan
facility: Department of Psychiatry, Hokkaido University Graduate School of Medicine
state: Sapporo
city: Kodaira
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo
city: Aichi
country: Japan
facility: Department of Psychiatry, Fujita Health University School of Medicine
state: Toyoake
city: London
country: United Kingdom
facility: Institute of Psychiatry, Psychology and Neuroscience,King's College London
state: England
Study officials:
affiliation: University of British Columbia, Department of Psychiatry
name: Lakshmi N Yatham, MBBS,MRCPsy
role: PRINCIPAL_INVESTIGATOR
References: