Study of the Efficacy of Lurasidone in Cognitive Functioning in Bipolar Patients (ELICE_BD)
Primary Purpose
Bipolar Disorder
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
lurasidone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Bipolar Disorder focused on measuring Bipolar Disorder, Cognition, Euthymic, Lurasidone
Eligibility Criteria
Inclusion Criteria:
- Males or females aged 19 to 65 years inclusive.
- 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.
- 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.
- All concomitant medication must be at a stable dose for two weeks prior to the randomization visit.
- Clinically stable during the last 4 weeks as assessed by clinical interview.
- A Montgomery Asberg Depression Rating Scale(MADRS) and Young Mania Rating Scale (YMRS) score less than or equal to 8.
- 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.
- A WAIS-IV vocabulary scaled score >5 (equivalent to estimated IQ 80 or greater).
- A sufficient level of the English or Japanese 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 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.
- 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:
- 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.
- Patients taking procognitive medications, clozapine, tricyclic antidepressants, first-generation antipsychotics, and cogentin.
- Those taking two or more antipsychotics.
- 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.
- 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 rTMS or tDCS or DBS within eight weeks or treatment with an experimental drug within 30 days.
- History of nonresponse or intolerance to lurasidone.
- Psychotic disorder other than Bipolar Disorder.
- Patients 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.
- Axis I diagnosis of alcohol/substance abuse or dependence within the past month.
- Significant risk of harm to self or others.
- Pregnancy or lactation.
- Liver function tests (AST and ALT) three times the upper limit of normal.
Sites / Locations
- The Brigham and Women's Hospital, Department of Psychiatry
- University Hospitals Cleveland Medical Center
- UBC Mood Disorders CenterRecruiting
- Department of Psychiatry, University of Occupational and Environmental HealthRecruiting
- Department of Neuropsychiatry, Kansai Medical UniversityRecruiting
- Department of Psychiatry, Hokkaido University Graduate School of MedicineRecruiting
- National Center of Neurology and PsychiatryRecruiting
- Department of Psychiatry, Fujita Health University School of MedicineRecruiting
- Institute of Psychiatry, Psychology and Neuroscience,King's College LondonRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Lurasidone
Placebo
Arm Description
Lurasidone 20 - 80 mg / day added to current treatment for 6 weeks.
Placebo added to current treatment for 6 weeks
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change in Depression
Montgomery Asberg Depression Rating Scale (MADRS) will be used to assess changes in bipolar depression from baseline to endpoint.
Change in Mania
The Young Mania Rating Scale (YMRS) will be used to assess changes in mania from baseline to endpoint.
Improvement in overall psychiatric status
Clinical Global Improvement Scale will be used to assess change from baseline to endpoint in overall psychiatric status.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02731612
Brief Title
Study of the Efficacy of Lurasidone in Cognitive Functioning in Bipolar Patients
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 8, 2017 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nazlin Walji
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder
Keywords
Bipolar Disorder, Cognition, Euthymic, Lurasidone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lurasidone
Arm Type
Experimental
Arm Description
Lurasidone 20 - 80 mg / day added to current treatment for 6 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo added to current treatment for 6 weeks
Intervention Type
Drug
Intervention Name(s)
lurasidone
Other Intervention Name(s)
Latuda
Intervention Description
Atypical Antipsychotic
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Inactive substance
Primary Outcome Measure Information:
Title
Improvement in cognitive performance in Euthymic bipolar patients treated with Lurasidone vs Placebo adjunctive therapy.
Description
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.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Change in Depression
Description
Montgomery Asberg Depression Rating Scale (MADRS) will be used to assess changes in bipolar depression from baseline to endpoint.
Time Frame
6 weeks
Title
Change in Mania
Description
The Young Mania Rating Scale (YMRS) will be used to assess changes in mania from baseline to endpoint.
Time Frame
6 weeks
Title
Improvement in overall psychiatric status
Description
Clinical Global Improvement Scale will be used to assess change from baseline to endpoint in overall psychiatric status.
Time Frame
6 weeks
Title
Improvement in Quality of Life
Description
Quality of Life, Bipolar Version Scale will be used to assess improvement in quality of life from baseline to endpoint.
Time Frame
6 weeks
Title
Improvement in Subjective-rated Cognitive Functioning
Description
Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) will be used to assess changes in subjective cognitive functioning from baseline to endpoint.
Time Frame
6 weeks
Title
Improvement in Objectively Rated Daily Functioning
Description
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.
Time Frame
6 weeks
Title
Improvement in Subjectively Rated Daily Functioning
Description
Sheehan Disability Scale (SDS) will be used to assess improvement in subjectively rated daily functioning, defined as change in scores from baseline to endpoint.
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or females aged 19 to 65 years inclusive.
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.
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.
All concomitant medication must be at a stable dose for two weeks prior to the randomization visit.
Clinically stable during the last 4 weeks as assessed by clinical interview.
A Montgomery Asberg Depression Rating Scale(MADRS) and Young Mania Rating Scale (YMRS) score less than or equal to 8.
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.
A WAIS-IV vocabulary scaled score >5 (equivalent to estimated IQ 80 or greater).
A sufficient level of the English or Japanese 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 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.
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:
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.
Patients taking procognitive medications, clozapine, tricyclic antidepressants, first-generation antipsychotics, and cogentin.
Those taking two or more antipsychotics.
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.
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 rTMS or tDCS or DBS within eight weeks or treatment with an experimental drug within 30 days.
History of nonresponse or intolerance to lurasidone.
Psychotic disorder other than Bipolar Disorder.
Patients 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.
Axis I diagnosis of alcohol/substance abuse or dependence within the past month.
Significant risk of harm to self or others.
Pregnancy or lactation.
Liver function tests (AST and ALT) three times the upper limit of normal.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nazlin Walji, B.Sc
Phone
604-822-7294
Email
nazlin.walji@ubc.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Jayasree Basivireddy, PhD
Phone
604-822-3769
Email
jayasree.basivireddy@ubc.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lakshmi N Yatham, MBBS,MRCPsy
Organizational Affiliation
University of British Columbia, Department of Psychiatry
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Brigham and Women's Hospital, Department of Psychiatry
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
UBC Mood Disorders Center
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 1Z3
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jayasree Basivireddy, PhD
Phone
604-822-3769
Email
jayasree.basivireddy@ubc.ca
First Name & Middle Initial & Last Name & Degree
Nazlin Walji, BSc.
Phone
604-822-7294
Email
nazlin.walji@ubc.ca
First Name & Middle Initial & Last Name & Degree
Lakshmi N Yatham
Facility Name
Department of Psychiatry, University of Occupational and Environmental Health
City
Kitakyushu
State/Province
Fukuoka
ZIP/Postal Code
807-8555
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reiji Yoshimura, MD, Ph.D
Phone
81-93-603-1611
Email
yoshi621@med.uoeh-u.ac.jp
First Name & Middle Initial & Last Name & Degree
Reiji Yoshimura, MD, Ph.D
Facility Name
Department of Neuropsychiatry, Kansai Medical University
City
Moriguchi-shi
State/Province
Osaka
ZIP/Postal Code
570-8506
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Masaki Kato, MD, Ph.D
Phone
81-6-6992-1001
Email
masaaki-ogasa@ds-pharma.co.jp
First Name & Middle Initial & Last Name & Degree
Masaki Kato, MD, Ph.D
Facility Name
Department of Psychiatry, Hokkaido University Graduate School of Medicine
City
Kita-ku
State/Province
Sapporo
ZIP/Postal Code
060-8638
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ichiro Kusumi, MD., Ph.D
Phone
81-11-706-5160
First Name & Middle Initial & Last Name & Degree
Ichiro Kusumi, MD, Ph.D
Facility Name
National Center of Neurology and Psychiatry
City
Kodaira
State/Province
Tokyo
ZIP/Postal Code
187-8551
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kazuyuki Nakagome, MD, Ph.D
Phone
81-42-341-2711
Ext
6200
Email
nakagome@guitar.ocn.ne.jp
First Name & Middle Initial & Last Name & Degree
Kazuyuki Nakagome, MD, Ph.D
Facility Name
Department of Psychiatry, Fujita Health University School of Medicine
City
Aichi
State/Province
Toyoake
ZIP/Postal Code
470-1192
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nakao Iwata, MD, Ph.D
Phone
81-562-93-2000
First Name & Middle Initial & Last Name & Degree
Nakao Iwata, MD, Ph.D
Facility Name
Institute of Psychiatry, Psychology and Neuroscience,King's College London
City
London
State/Province
England
ZIP/Postal Code
SE5 8AF
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elliot Hampsey, MSc.
Email
elliot.hampsey@kcl.ac.uk
First Name & Middle Initial & Last Name & Degree
Andrea M Ulrichsen, MBBS
Email
andrea.ulrichsen@kcl.ac.uk
First Name & Middle Initial & Last Name & Degree
Allan Young, MB.ChB, Mphil, PhD,
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of the Efficacy of Lurasidone in Cognitive Functioning in Bipolar Patients
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