Comparative Effectiveness Study for Bipolar Disorder

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Andrew A. Nierenberg, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01331304
First received: April 6, 2011
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to compare the effectiveness of lithium and quetiapine for the treatment of individuals with bipolar disorder.


Condition Intervention Phase
Bipolar Disorder
Drug: Lithium
Drug: Quetiapine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer And a Classic Mood Stabilizer for Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Clinical Global Impression-Efficacy Index (CGI-EI) [ Time Frame: Average 6 month score minus Average baseline score ] [ Designated as safety issue: Yes ]
    The CGI-EI integrates benefits and harms and yields a score that can be compared across interventions. It is made up of 2 subscales: therapeutic effects and side effects. Each rating is on a scale from 1 to 4. To combine these two subscales into the CGI-EI we report as our primary outcome, we subtracted the side effects subscale from the therapeutic effects subscale. Thus, the CGI-EI we report ranges the integers from -3 to +3 (i.e. possible scores are -3,-2,-1,0,1,2,3). A score of -3 is the most burdensome side effect score (4) and the least therapeutic effect score (1) and a score of +3 is the least burdensome side effect score (1) and the highest therapeutic effect score (4). Higher CGI-EI signifies better outcome (minimal side effects, maximal therapeutic effect). Lower CGI-EI signifies worse outcome (maximal side effects, minimal therapeutic effect).To compute CGI-EI score, we subtract the side effect score from the therapeutic effect score.

  • Necessary Clinical Adjustments [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]
    Necessary Clinical Adjustment (NCA): The Medication Recommendation Tracking Form was developed and successfully implemented in a previous study to capture recommended medication changes at each study visit 17. Clinicians record dosage changes, missed doses, new medications added or discontinued, and specify the reason for each change. Any change in psychotropic medications, or medications used to treat side effects, is coded along with the reason for the change. NCAs include those changes made for lack of effectiveness or intolerance, but not changes for planned dose titrations.


Secondary Outcome Measures:
  • Risk of Cardiovascular Disease - Framingham Risk Score [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    The Framingham risk score captures the classic risk factors for cardiovascular disease, including age, sex, systolic blood pressure, total and high density lipoprotein cholesterol, diabetes mellitus, and smoking. The Framingham risk score is used as a simple predictive tool to determine 10-year (short term) risk for developing cardiovascular disease (CHD).

  • Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    The LIFE-RIFT asses the extent to which psychopathology has impacted current functioning in work, household chores, interpersonal relationships with partner, family, and friends, recreational activities, and life, satisfaction, leisure activities and social relationships.


Enrollment: 482
Study Start Date: September 2010
Study Completion Date: September 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Li + APT
Study participants will take lithium in addition to any other medications recommended by the study physician.
Drug: Lithium
600-900mg per day over 6 months
Other Name: Lithoboid, Eskalith
QTP + APT
Study participants will take quetiapine in addition to any other medications recommended by the study physician.
Drug: Quetiapine
100-800mg a day over 6 months
Other Name: Seroquel

Detailed Description:

Mood stabilizers, medications that prevent future mood episodes, are the foundation for treatment of bipolar disorder. While all published bipolar disorder treatment guidelines recommend that pharmacotherapy should include mood stabilizers for long-term maintenance treatment, no randomized comparative effectiveness studies have examined the real-world advantages and disadvantages of the newer second generation antipsychotic (SGA) mood stabilizers compared to the classic mood stabilizers, such as lithium (Li). No studies have looked at the effectiveness of SGAs compared to mood stabilizers when used in the context of other medications required to manage bipolar patients, since bipolar disorder patients take a median of 3 medications for optimal outcomes. Quetiapine (QTP) is the most extensively studied, broadly efficacious and the most widely prescribed SGA for bipolar disorder. The classic mood stabilizer Li has the largest evidence base for treating bipolar disorder, but has been largely supplanted by the SGAs.

Thus, this study compares symptomatic benefits and adverse effect burden between a QTP foundation with adjunctive personalized treatments (QTP+APT) and a mood stabilizer foundation consisting of Li with APT (Li+APT). APT will include any other medication needed with the following exceptions: the QTP+APT cannot receive Li and the Li+APT group cannot receive an antipsychotic. If, however, participants clinically require a switch to, or the addition of any other SGA or mood stabilizer, then those medications can be added as a rescue strategy that will be carefully recorded. Consistent with an effectiveness trial, participants will be able to continue in the study if they require a rescue treatment. The specific plan is a randomized, open, two arm, comparative effectiveness study of QTP+APT vs. Li+APT treatment for 6 months across 10 sites.

In summary, this comparative effectiveness study compares fundamentally different acute and continuation treatments for bipolar disorder. The investigators address the key question of whether to use a prototypical mood stabilizing SGA (i.e., QTP) or the classical mood stabilizer Li as the foundational treatment in the context of other necessary adjunctive personalized treatments (APT).

  Eligibility

Ages Eligible for Study:   18 Years to 68 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Meets DSM-IV criteria for BD I or II, which is the primary focus of treatment
  2. Able to give written informed consent
  3. Age > to 18 years and < 68 years
  4. Women of child bearing potential must agree to use adequate contraception (e.g. oral contraceptives, intrauterine device, barrier methods, or total abstinence from intercourse; Depo Provera is acceptable if it is started 3 months prior to enrollment), inform their doctor at the earliest possible time of their plans to conceive, and to understand the risks of lithium and other study treatments to the fetus and infant
  5. Currently symptomatic, as defined as a Clinical Global Impression - Bipolar Disorder Overall Severity (CGI-BP-S) score of at least 3 (mild)
  6. If currently taking an SGA, participants would be required to be willing to either discontinue or switch to QTP
  7. Willing to be randomized to either QTP+APT or Li+APT.

Exclusion Criteria:

  1. Unwilling or unable to comply with study requirements
  2. If maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1
  3. Patients who have had intolerable side effects with QTP or Li
  4. Patients whose clinical status requires inpatient care
  5. Drug/alcohol dependence within the past 30 days
  6. Pregnancy as determined by urine pregnancy test or breastfeeding
  7. History of nonresponse to Li at a serum level of ≥ 1.0 mEq/L ≥ 8 weeks
  8. History of nonresponse to QTP at doses of at least 600 mg ≥ 8 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: NCT01331304

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35205
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065
United States, Ohio
Case Western Reserve University School of Medicine
Cleveland, Ohio, United States, 44106
The Lindner Center of HOPE
Mason, Ohio, United States, 45040
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37212
United States, Texas
The University of Texas Health Science Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Andrew A Nierenberg, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Andrew A. Nierenberg, MD, Director of Research, Bipolar Clinic and Research Program, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01331304     History of Changes
Other Study ID Numbers: R01 HS019371-01
Study First Received: April 6, 2011
Results First Received: January 8, 2014
Last Updated: May 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Bipolar disorder
Comparative effectiveness trial
Lithium
Quetiapine

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Lithium
Quetiapine
Lithium Carbonate
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antimanic Agents
Antidepressive Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014