Sequential Multiple Assignment Treatment for Bipolar Disorder (SMART)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2012 by The University of Texas Health Science Center at San Antonio
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Charles L. Bowden, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier:
NCT01588457
First received: February 29, 2012
Last updated: November 19, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to compare which of the two mood stabilizers (drugs that help to steady/stabilize mood in patients with bipolar disorder (BD)), lithium and divalproex, is more effective in patients with bipolar disorder over 26 weeks. The study will also compare if lithium or divalproex used alone versus lithium or divalproex used with quetiapine versus lithium or divalproex used with lamotrigine is more effective when symptoms of depression develop.


Condition Intervention Phase
Bipolar I Disorder
Bipolar II Disorder
Drug: Lithium/Lithium Carbonate
Drug: Divalproex
Drug: Lamotrigine
Drug: Quetiapine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Sequential Multiple Assignment Randomized Treatment (SMART)for Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Bipolar Inventory of Symptoms Scale (BISS) [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Global Assessment of Functioning Scale (GAF) [ Time Frame: Baseline and 26 weeks ] [ Designated as safety issue: No ]
    Rating scale used to rate the social, occupational, and psychological functioning of adults.


Estimated Enrollment: 200
Study Start Date: June 2011
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Lithium/Lithium Carbonate
Therapeutic dosage as indicated by participants condition with blood levels. LI will be dosed to attain LI of ≥0.5mEq/L.
Other Name: Lithium Carbonate
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.
Drug: Divalproex
DV will be dosed to attain DV levels of ≥45mg/L.
Other Names:
  • Depakote
  • Depakote ER
Active Comparator: Lithium plus Quetiapine
Those who develop protocol defined depression will then be randomized to a mood stabilizer (lithium) + quetiapine [QT].
Drug: Lithium/Lithium Carbonate
Therapeutic dosage as indicated by participants condition with blood levels. LI will be dosed to attain LI of ≥0.5mEq/L.
Other Name: Lithium Carbonate
Drug: Quetiapine
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 Name: Seroquel
Active Comparator: Lithium plus Lamotrigine
Those who develop protocol defined depression will then be randomized to a mood stabilizer (lithium) + lamotrigine (LM).
Drug: Lithium/Lithium Carbonate
Therapeutic dosage as indicated by participants condition with blood levels. LI will be dosed to attain LI of ≥0.5mEq/L.
Other Name: Lithium Carbonate
Drug: Lamotrigine
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 Name: Lamictal
Active Comparator: Divalproex plus Quetiapine
Those who develop protocol defined depression will then be randomized to a mood stabilizer (divalproex) + quetiapine [QT].
Drug: Divalproex
DV will be dosed to attain DV levels of ≥45mg/L.
Other Names:
  • Depakote
  • Depakote ER
Drug: Quetiapine
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 Name: Seroquel
Active Comparator: Divalproex plus Lamotrigine
Those who develop protocol defined depression will then be randomized to a mood stabilizer (divalproex) + lamotrigine (LM).
Drug: Divalproex
DV will be dosed to attain DV levels of ≥45mg/L.
Other Names:
  • Depakote
  • Depakote ER
Drug: Lamotrigine
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 Name: Lamictal

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 [DV]. Those who develop protocol defined depression will then be randomized to a MS alone, MS + quetiapine [QT] or MS + lamotrigine [LM]. 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.

Aim A.2 Compare the effectiveness of LI to DV as a primary component of treatment for BD over 26 weeks.

Aim A.3: Assess the effectiveness of MS + QT and MS + LM 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).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • DSM-IV TR diagnosis BD I or II as assessed by MINI 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 QT, LI, DV, or LM
  • 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 or DV at a serum level of ≥ 45 mg/dL for at least 2 weeks.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01588457

Contacts
Contact: Martha L. Dahl, RN 210-567-0996 dahlml@uthscsa.edu
Contact: Melissa A Hernandez, MA 210-567-0956 hernandezma0@uthscsa.edu

Locations
United States, Ohio
Case Western Reserve University Recruiting
Cleveland, Ohio, United States, 44106
Contact: Carla Conroy    216-844-2871    carla.conroy@uhhospitals.org   
Principal Investigator: Joseph Calabrese, M.D.         
United States, Texas
University of Texas Health Science Center Recruiting
San Antonio, Texas, United States, 78229-3900
Contact: Martha L. Dahl, RN    210-567-0956    dahlml@uthscsa.edu   
Sub-Investigator: Mauricio Tohen, M.D.         
Sub-Investigator: Peter Thompson, M.D.         
Sub-Investigator: Marlon Quinones, M.D.         
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Investigators
Principal Investigator: Charles L. Bowden, M.D. University of Texas
Principal Investigator: Joseph R Calabrese, M.D. Case Western Reserve University
Principal Investigator: Vivek Singh, M.D. University of Texas
  More Information

No publications provided

Responsible Party: Charles L. Bowden, Professor/Clinical Psychiatry, The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT01588457     History of Changes
Other Study ID Numbers: HSC20110361H, 1P30MH086045-01A2
Study First Received: February 29, 2012
Last Updated: November 19, 2012
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Lamotrigine
Valproic Acid
Anticonvulsants
Lithium Carbonate
Lithium
Quetiapine
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Antipsychotic Agents
Antidepressive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Cardiovascular Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on August 28, 2014