Comparative Effectiveness Study for Bipolar Disorder

NCT01331304 | Completed Phase 4 Results DMC

• 2 other identifiers: 2010P001442R01HS019371-01
• Study Type: interventional
• Target: 482
• Locations: 1 country
• Sites: 11

Brief Summary

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

Conditions

Bipolar Disorder

Keywords

Bipolar disorder; Comparative effectiveness trial; Lithium; Quetiapine

Outcome Measures

Primary Outcomes (2)

• Clinical Global Impression-Efficacy Index (CGI-EI)

  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.

  Average 6 month score minus Average baseline score

• Necessary Clinical Adjustments

  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.

  6 Months

Secondary Outcomes (2)

• Risk of Cardiovascular Disease - Framingham Risk Score

  Average baseline score minus Average 6 month score

• Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT)

  Average baseline score minus Average 6-month score

Study Arms (2)

Li + APT

OTHER

Study participants will take lithium in addition to any other medications recommended by the study physician.

Drug: Lithium

QTP + APT

OTHER

Study participants will take quetiapine in addition to any other medications recommended by the study physician.

Drug: Quetiapine

Interventions

Lithium DRUG

600-900mg per day over 6 months

Also known as: Lithoboid, Eskalith

Li + APT

Quetiapine DRUG

100-800mg a day over 6 months

Also known as: Seroquel

QTP + APT

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets DSM-IV criteria for BD I or II, which is the primary focus of treatment
• Able to give written informed consent
• Age \> to 18 years and \< 68 years
• 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
• Currently symptomatic, as defined as a Clinical Global Impression - Bipolar Disorder Overall Severity (CGI-BP-S) score of at least 3 (mild)
• If currently taking an SGA, participants would be required to be willing to either discontinue or switch to QTP
• Willing to be randomized to either QTP+APT or Li+APT.

You may not qualify if:

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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Agency for Healthcare Research and Quality (AHRQ): collaborator

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35205, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Case Western Reserve University School of Medicine

Cleveland, Ohio, 44106, United States

Location

The Lindner Center of HOPE

Mason, Ohio, 45040, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

The University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

Related Publications (4)

• Sylvia LG, Montana RE, Deckersbach T, Thase ME, Tohen M, Reilly-Harrington N, McInnis MG, Kocsis JH, Bowden C, Calabrese J, Gao K, Ketter T, Shelton RC, McElroy SL, Friedman ES, Rabideau DJ, Nierenberg AA. Poor quality of life and functioning in bipolar disorder. Int J Bipolar Disord. 2017 Dec;5(1):10. doi: 10.1186/s40345-017-0078-4. Epub 2017 Mar 27.

  PMID: 28188565 DERIVED

• Deckersbach T, Nierenberg AA, McInnis MG, Salcedo S, Bernstein EE, Kemp DE, Shelton RC, McElroy SL, Sylvia LG, Kocsis JH, Bobo WV, Friedman ES, Singh V, Tohen M, Bowden CL, Ketter TA, Calabrese JR, Thase ME, Reilly-Harrington NA, Rabideau DJ, Kinrys G, Kamali M. Baseline disability and poor functioning in bipolar disorder predict worse outcomes: results from the Bipolar CHOICE study. J Clin Psychiatry. 2016 Jan;77(1):100-8. doi: 10.4088/JCP.14m09210.

  PMID: 26845265 DERIVED

• Nierenberg AA, McElroy SL, Friedman ES, Ketter TA, Shelton RC, Deckersbach T, McInnis MG, Bowden CL, Tohen M, Kocsis JH, Calabrese JR, Kinrys G, Bobo WV, Singh V, Kamali M, Kemp D, Brody B, Reilly-Harrington NA, Sylvia LG, Shesler LW, Bernstein EE, Schoenfeld D, Rabideau DJ, Leon AC, Faraone S, Thase ME. Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness): a pragmatic 6-month trial of lithium versus quetiapine for bipolar disorder. J Clin Psychiatry. 2016 Jan;77(1):90-9. doi: 10.4088/JCP.14m09349.

  PMID: 26845264 DERIVED

• Bobo WV, Reilly-Harrington NA, Ketter TA, Brody BD, Kinrys G, Kemp DE, Shelton RC, McElroy SL, Sylvia LG, Kocsis JH, McInnis MG, Friedman ES, Singh V, Tohen M, Bowden CL, Deckersbach T, Calabrese JR, Thase ME, Nierenberg AA, Rabideau DJ, Schoenfeld DA, Faraone SV, Kamali M. Complexity of illness and adjunctive benzodiazepine use in outpatients with bipolar I or II disorder: results from the Bipolar CHOICE study. J Clin Psychopharmacol. 2015 Feb;35(1):68-74. doi: 10.1097/JCP.0000000000000257.

  PMID: 25514063 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Lithium; Lithium Carbonate; Quetiapine Fumarate

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals; Carbonates; Alkalies; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds; Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Andrew Nierenberg
• Organization: Massachusetts General Hospital

anierenberg@mgh.harvard.edu

617-724-0837

Study Officials

• Andrew A Nierenberg, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research, Bipolar Clinic and Research Program

Study Record Dates

• First Submitted: April 6, 2011
• First Posted: April 8, 2011
• Study Start: September 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: September 1, 2013
• Last Updated: April 26, 2018
• Results First Posted: June 4, 2014

Record last verified: 2018-03

Locations

US (11)