- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01588457
Sequential Multiple Assignment Treatment for Bipolar Disorder (SMART)
Sequential Multiple Assignment Randomized Treatment (SMART) for Bipolar Disorder
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This open methods advancement study will randomize BD patients with clinically significant symptoms to treatment with one of two mood stabilizers (MS), lithium [Li] or divalproex [Div]. Those who develop protocol defined depression will then be randomized to a MS alone, MS + quetiapine [QTP] or MS + lamotrigine [LTG]. A SMART strategy employs a rule for adding new treatments based on each patient's current illness state and response during the trial, mimicking the adaptive nature of treatment selection which occurs in clinical settings, but in a controlled way which allows application of causal inference. By using early indices of response to dynamically alter treatment decisions to improve outcome, SMART eliminates unmeasured confounders associated with treatment decisions that are not randomized, as occurs in data mining exercises and in other non-randomized decisions in studies which randomize one variable at baseline. This sequential adaptive design represents a methodological innovation in bipolar trial history which will have particular implications for effectiveness studies.
Specific Aim A.1: Assess the feasibility of a SMART design in the conduct of an effectiveness study over 26 weeks in patients with BD (bipolar disorder).
Aim A.2 Compare the effectiveness of Li to Div as a primary component of treatment for BD over 26 weeks.
Aim A.3: Assess the effectiveness of MS + QTP and MS + LTG versus MS in subjects who develop depression.
A4. Exploratory Aims: 1.Determine the effects of ethnicity, language facility, education and stress as moderators of treatment outcomes; 2. Explore the use of novel statistical methodologies to more informatively characterize illness trajectories in response to the interventions. In the aggregate these aims also will clarify whether the SMART confirms results provided by traditional, single point randomized controlled trials (RCTs).
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Ohio
-
Cleveland, Ohio, United States, 44106
- Case Western Reserve University
-
-
Texas
-
San Antonio, Texas, United States, 78229-3900
- University of Texas Health Science Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- DSM-IV TR (Diagnostic and Statistical Manual Edition IV Text Revision) diagnosis BD I or II as assessed by MINI PLUS (Mini International Neuropsychiatric Interview PLUS)
- Male or female ≥ 18 years old
- Currently symptomatic with a CGI-BP-S ≥3 for mania/hypomania &/or depression for ≥ 2 weeks
- One of the following indicators of recent active illness: a depressive or manic or hypomanic or mixed episode in the past 12 months
- If female of child bearing age must use effective birth control.
Exclusion Criteria:
- Unwilling or unable to comply with study requirements
- Renal impairment (serum creatinine > 1.5 mg/dL)
- If maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1
- Patients who have had intolerable side effects to QTP, Li, Div, or LTG
- Patients whose clinical status requires inpatient care
- Drug/alcohol dependence within the past 30 days
- Pregnancy as determined by serum pregnancy test or breastfeeding
- History of poor response to Li at a serum Li of ≥ 0.5 mEq/L (milliequivalents per Liter) or Div at a serum level of ≥ 45 mg/dL for at least 2 weeks.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Lithium
This open methods advancement study will randomize BD patients with clinically significant symptoms to treatment with one of two mood stabilizers, lithium [Li] at baseline.
Lithium is one of these two mood stabilizers.
The person may or may not stay solely on lithium throughout the study.
|
Therapeutic dosage as indicated by participants condition with blood levels.
LI will be dosed to attain Li of ≥0.5mEq/L (milliequivalents per liter).
Other Names:
|
Active Comparator: Divalproex
This open methods advancement study will randomize BD patients with clinically significant symptoms to treatment with one of two mood stabilizers, divalproex (DV)at baseline.
Divalproex is one of these two mood stabilizers.
The person may or may not stay solely on divalproex throughout the study.
|
DV will be dosed to attain DV levels of ≥45mg/L.
Other Names:
|
Active Comparator: Lithium plus Quetiapine
Those who develop protocol defined depression will then be randomized to a mood stabilizer (lithium) + quetiapine [QT].
|
Therapeutic dosage as indicated by participants condition with blood levels.
LI will be dosed to attain Li of ≥0.5mEq/L (milliequivalents per liter).
Other Names:
QT will be started at 50 mg/day and titrated up to 300 mg as tolerated.
QT will be discontinued if not tolerated at 100mg/day and the patient will be treated according to guidelines.
Other Names:
|
Active Comparator: Lithium plus Lamotrigine
Those who develop protocol defined depression will then be randomized to a mood stabilizer (lithium) + lamotrigine (LM).
|
Therapeutic dosage as indicated by participants condition with blood levels.
LI will be dosed to attain Li of ≥0.5mEq/L (milliequivalents per liter).
Other Names:
LM will be incrementally dosed up to 400 mg/day, or, in combination with DV, 200 mg/day.
Dosage may be reduced for adverse effects to one half of the target dose.
Other Names:
|
Active Comparator: Divalproex plus Quetiapine
Those who develop protocol defined depression will then be randomized to a mood stabilizer (divalproex) + quetiapine [QT].
|
DV will be dosed to attain DV levels of ≥45mg/L.
Other Names:
QT will be started at 50 mg/day and titrated up to 300 mg as tolerated.
QT will be discontinued if not tolerated at 100mg/day and the patient will be treated according to guidelines.
Other Names:
|
Active Comparator: Divalproex plus Lamotrigine
Those who develop protocol defined depression will then be randomized to a mood stabilizer (divalproex) + lamotrigine (LM).
|
DV will be dosed to attain DV levels of ≥45mg/L.
Other Names:
LM will be incrementally dosed up to 400 mg/day, or, in combination with DV, 200 mg/day.
Dosage may be reduced for adverse effects to one half of the target dose.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Bipolar Inventory of Symptoms Scale (BISS)
Time Frame: Change from Baseline to 26 weeks
|
The BISS uses a structured interview to assess the full spectrum of symptoms associated with all primary clinical states in bipolar disorder, yielding a total severity, a depression, a mania, as well as dimensional scale scores. There are 42 items; each item is rated on a 0-4 scale. The BISS is a clinician-rated instrument. The Scale is rated as follows: 0 Not at all
|
Change from Baseline to 26 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Global Assessment of Functioning
Time Frame: Change from Baseline to 26 weeks
|
The Clinical Global Impression-Severity Scale (CGI-S) is used to assess global illness severity The CGI-S score change is measured from baseline to 26 weeks and is rated on a 7-point scale. The scale is read as follows:
|
Change from Baseline to 26 weeks
|
Baseline Randomization Percentage of Bipolar Types
Time Frame: Baseline
|
Percentages of Type I and Type II Bipolar Disorder included in Randomization groups
|
Baseline
|
Demographic in Randomization 1 Group
Time Frame: Baseline
|
Baseline demographic percentages of subject randomized to either Divalproex or Lithium at the first randomization
|
Baseline
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Charles L. Bowden, M.D., University of Texas
- Principal Investigator: Joseph R Calabrese, M.D., Case Western Reserve University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Pathologic Processes
- Bipolar and Related Disorders
- Disease
- Bipolar Disorder
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Membrane Transport Modulators
- Antidepressive Agents
- GABA Agents
- Anticonvulsants
- Sodium Channel Blockers
- Antimanic Agents
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Lamotrigine
- Valproic Acid
- Quetiapine Fumarate
- Lithium Carbonate
Other Study ID Numbers
- HSC20110361H
- 1P30MH086045-01A2 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Bipolar I Disorder
-
ProgenaBiomeRecruitingBipolar Disorder | Bipolar I Disorder | Bipolar II Disorder | Bipolar Type I Disorder | Bipolar Disorder Mild | Bipolar Disorder Moderate | Bipolar Disorder SevereUnited States
-
Rush University Medical CenterThe Ryan Licht Sang Bipolar FoundationCompletedBipolar Disorder | Bipolar Depression | Bipolar I Disorder | Bipolar Disorder I | Bipolar Affective DisorderUnited States
-
Otsuka Pharmaceutical Development & Commercialization...H. Lundbeck A/SCompletedBipolar I DisorderUnited States, Taiwan, Romania, Korea, Republic of, Japan, Poland, Canada
-
Professor Saad ShakirMerck Sharp & Dohme LLCCompletedBipolar I DisorderUnited Kingdom
-
Solvay PharmaceuticalsWyeth is now a wholly owned subsidiary of Pfizer; H. Lundbeck A/SCompleted
-
University of Sao PauloCompleted
-
University of Sao PauloUnknown
-
Merck Sharp & Dohme LLCRecruitingBipolar I DisorderUnited States
-
Roxane LaboratoriesCompletedBipolar I DisorderUnited States
-
Eli Lilly and CompanyCompletedBipolar I DisorderUnited States
Clinical Trials on Lithium
-
University of CincinnatiUnknownBipolar I DisorderUnited States
-
Brigham and Women's HospitalRecruitingDepression | Bipolar Disorder | Bipolar Depression | Major Depressive Episode | Bipolar I Depression | Bipolar II DepressionUnited States
-
University of Maryland, BaltimoreCompletedOsteoporosis PseudogliomaUnited States
-
Northwestern UniversityCompletedBipolar DisorderUnited States
-
New York State Psychiatric InstituteNational Institute on Aging (NIA)CompletedPsychosis | Alzheimer's Disease | AgitationUnited States
-
Region StockholmRigshospitalet, DenmarkRecruitingCognitive Impairment | Brain Tumor | Cognitive Decline | Memory Impairment | Radiotherapy Side Effect | Radiotherapy; Complications | Late Effect of RadiationSweden
-
University of PennsylvaniaNational Institute of Mental Health (NIMH)Completed
-
University of OxfordCompleted
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedPrimary Myelofibrosis | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Chronic Myelomonocytic Leukemia | Recurrent Adult Acute Myeloid Leukemia | Juvenile Myelomonocytic Leukemia | Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal... and other conditionsUnited States
-
Vanderbilt-Ingram Cancer CenterNational Cancer Institute (NCI)TerminatedSolid Tumor | Brain and Central Nervous System Tumors | Neurotoxicity | Cognitive/Functional EffectsUnited States