AzTrials
AzTrials

Bipolar DisorderPhase 4NCT01331304

Comparative Effectiveness Study for Bipolar Disorder

A Phase 4 study testing Lithium and Quetiapine in people with Bipolar Disorder, run by Massachusetts General Hospital at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 to 68 years
Conditions the study is for
Bipolar Disorder
What is being tested?
Lithium and Quetiapine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
482 participants
Where
11 sitesUnited States
Study dates
Sep 2010to Sep 2013
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 68 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35205

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Case Western Reserve University School of Medicine

    Cleveland, Ohio, 44106

  • The Lindner Center of HOPE

    Mason, Ohio, 45040

  • Vanderbilt University

    Nashville, Tennessee, 37212

  • Weill Cornell Medical College

    New York, New York, 10065

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

  • The University of Texas Health Science Center

    San Antonio, Texas, 78229

  • Stanford University School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer And a Classic Mood Stabilizer for Bipolar Disorder

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

Read the 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).

Being tested
Lithium, Quetiapine
Keywords
Bipolar disorder, Comparative effectiveness trial, Lithium, Quetiapine
Medical subject headings
Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LithiumDrug

    Also called Lithoboid, Eskalith

    600-900mg per day over 6 months

  • QuetiapineDrug

    Also called Seroquel

    100-800mg a day over 6 months

Study groups in NCT01331304
Study groupRoleWhat they receive
Li + APTOtherStudy participants will take lithium in addition to any other medications recommended by the study physician.
Receives: Drug: Lithium
QTP + APTOtherStudy participants will take quetiapine in addition to any other medications recommended by the study physician.
Receives: Drug: Quetiapine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Average 6 month score minus Average baseline score

  2. 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.

    Measured: 6 Months

Secondary outcomes (2)

  1. Risk of Cardiovascular Disease - Framingham Risk Score

    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), with higher scores indicating higher risk. Established benchmarks exist for scores from 0 to 25--though it can exceed this value--that are meant to translate to the probability of developing heart disease.

    Measured: Average baseline score minus Average 6 month score

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

    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. Summary scores can range from 4 to 20, with higher scores indicating greater functional impairment.

    Measured: Average baseline score minus Average 6-month score

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2011 (estimated)
  2. Study startSep 2010
  3. Primary completionApr 2013
  4. Study completionSep 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
482 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01331304
Sponsor's protocol ID
2010P001442
Other IDs
R01HS019371-01
Status last verified
Mar 2018
First submitted
6 Apr 2011
Last updated
26 Apr 2018
Data monitoring committee
Yes

Publications

  • Wrobel AL, Dean OM, Lotfaliany M, Berk M, Sylvia LG, Thase ME, Deckersbach T, Tohen M, McInnis MG, Kocsis JH, Shelton RC, McElroy SL, Turner A, Nierenberg AA. Potential Impact of Childhood Abuse on Quality of Life During Mood-Stabilising Treatment in Individuals Living With Bipolar Disorder. Bipolar Disord. 2026 Mar;28(2):e70079. doi: 10.1111/bdi.70079.

    PubMed 41677164

  • 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.

    PubMed 28188565

  • 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.

    PubMed 26845265

  • 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.

    PubMed 26845264

  • 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.

    PubMed 25514063

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Lithium and Quetiapine in people with Bipolar Disorder, run by Massachusetts General Hospital at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical Global Impression-Efficacy Index (CGI-EI) (time frame: Average 6 month score minus Average baseline score). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01331304, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
Comparative Effectiveness Study for Bipolar Disorder | AzTrials