NCT00667745

Brief Summary

This study evaluated whether lithium included as part of optimized medication treatment improved overall level of illness, symptoms of mania and depression, and quality of life in people with bipolar disorder.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
283

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Apr 2008

Geographic Reach
1 country

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2008

Completed
23 days until next milestone

First Submitted

Initial submission to the registry

April 24, 2008

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 28, 2008

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2010

Completed
3.3 years until next milestone

Results Posted

Study results publicly available

June 28, 2013

Completed
Last Updated

February 13, 2018

Status Verified

July 1, 2010

Enrollment Period

1.9 years

First QC Date

April 24, 2008

Results QC Date

October 25, 2012

Last Update Submit

January 17, 2018

Conditions

Bipolar Disorder

Keywords

LithiumSymptomsMedication Changes

Outcome Measures

Primary Outcomes (2)

  • Overall Change in Bipolar Illness Severity as Measured by Clinical Global Impression for Bipolar Disorder Severity (CGI-BP-S) Score

    Scale: Clinical Global Impression for Bipolar Disorder Severity (CGI-BP-S) Construct: This scale holistically measures severity of a participant's depression, mania, and overall illness. Range: 0- not assessed, 1-normal (not at all ill), 2- borderline mentally ill, 3- mildly ill, 4- moderately ill, 5- markedly ill, 6- severely ill, 7- among the most extremely ill patients.

    Relevant time points: baseline and week 24

  • Number of Necessary Medication Adjustments

    Metric Definition (Necessary Clinical Adjustments (NCA)): Medication adjustments to reduce symptoms, optimize treatment response and functioning, or to address intolerable side effects. This was determined with the Medication Recommendation Tracking Form (MRTF), a novel method for capturing physician prescribing behavior and clinical decision making. Range: whole numbers Relevant time points: Weeks 2, 4, 6, 8, 12, 16, 20, and 24.

    Measured over 6 months

Secondary Outcomes (3)

  • Depression Symptoms as Measured Self Report Montgomery Asberg Depression Rating Scale (MADRS)

    Measured over 6 months

  • Mania Symptoms as Measured by the Young Mania Rating Scale (YMRS)

    Measured over 6 months

  • Suicidality as Measured by the Modified Scale for Suicidal Ideation (MSSI)

    Measured over 6 months

Study Arms (2)

1

EXPERIMENTAL

Participants received lithium plus optimized medication treatment, as needed.

Drug: Lithium CarbonateDrug: Optimized Treatment (OPT)

2

ACTIVE COMPARATOR

Participants only received optimized medication treatment, as needed; lithium was not be used.

Drug: Optimized Treatment (OPT)

Interventions

Lithium CarbonateDRUG

Lithium was started at 300 mg and then increased to 600 mg after 3 days. Lithium doses were maintained at 600 mg per day for 8 weeks, but may have been adjusted after that time as needed up to a serum level of 1.2 mEq/L.

Also known as: Lithium
1
Optimized Treatment (OPT)DRUG

The foundation of OPT was to maintain treatment that will typically include at least one FDA-approved mood stabilizer other than lithium (e.g., divalproex, carbamazepine, risperidone, quetiapine, olanzapine, aripiprazole, ziprasidone) and to follow the recommendations summarized in the evidence-based stages of the Texas Implementation of Medication Algorithm (TIMA) revised guidelines.

12

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Meets DSM-IV Criteria for bipolar disorder (type I or II)
  • Currently symptomatic, as defined as a Clinical Global Impressions Scale-Bipolar Version, Overall Severity Index (CGI-BP-S) of greater than or equal to 3
  • If taking or has taken lithium, must be off lithium for at least 30 days before study entry
  • If a woman of child bearing potential, agrees to inform their doctor at the earliest possible time of their plans to conceive, to use adequate contraception (e.g. oral contraceptives, intrauterine device, barrier methods, total abstinence from intercourse), and to acknowledge the risks of lithium to the fetus and infant (Depo Provera is acceptable if it is started 3 months before study entry)

You may not qualify if:

  • Renal impairment (serum creatinine greater than 1.5 mg/dL)
  • Thyroid stimulating hormone (TSH) over 20% above the upper normal limit (participants maintained on thyroid medication must be euthyroid for at least 3 months before Visit 1)
  • History of lithium toxicity that was not caused by mismanagement or overdose
  • Other contraindication to lithium (e.g., hypersensitivity to lithium or any component of the formulation, severe cardiovascular or renal disease, severe debilitation, dehydration, sodium depletion, pregnancy)
  • Currently in crisis such that inpatient hospitalization or other crisis - Participated in a clinical trial of an investigational drug within the 1 months before study entry
  • Pregnant or breastfeeding

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Stanford University

Stanford, California, 94035-5723, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

Related Publications (5)

  • Ostacher MJ, Nierenberg AA, Rabideau D, Reilly-Harrington NA, Sylvia LG, Gold AK, Shesler LW, Ketter TA, Bowden CL, Calabrese JR, Friedman ES, Iosifescu DV, Thase ME, Leon AC, Trivedi MH. A clinical measure of suicidal ideation, suicidal behavior, and associated symptoms in bipolar disorder: Psychometric properties of the Concise Health Risk Tracking Self-Report (CHRT-SR). J Psychiatr Res. 2015 Dec;71:126-33. doi: 10.1016/j.jpsychires.2015.10.004. Epub 2015 Oct 9.

    PMID: 26476489DERIVED

  • Reilly-Harrington NA, Sylvia LG, Leon AC, Shesler LW, Ketter TA, Bowden CL, Calabrese JR, Friedman ES, Ostacher MJ, Iosifescu DV, Rabideau DJ, Thase ME, Nierenberg AA. The Medication Recommendation Tracking Form: a novel tool for tracking changes in prescribed medication, clinical decision making, and use in comparative effectiveness research. J Psychiatr Res. 2013 Nov;47(11):1686-93. doi: 10.1016/j.jpsychires.2013.07.009. Epub 2013 Jul 30.

    PMID: 23911057DERIVED

  • Beech RD, Leffert JJ, Lin A, Sylvia LG, Umlauf S, Mane S, Zhao H, Bowden C, Calabrese JR, Friedman ES, Ketter TA, Iosifescu DV, Reilly-Harrington NA, Ostacher M, Thase ME, Nierenberg A. Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (LiTMUS). Pharmacogenomics J. 2014 Apr;14(2):182-91. doi: 10.1038/tpj.2013.16. Epub 2013 May 14.

    PMID: 23670706DERIVED

  • Nierenberg AA, Friedman ES, Bowden CL, Sylvia LG, Thase ME, Ketter T, Ostacher MJ, Leon AC, Reilly-Harrington N, Iosifescu DV, Pencina M, Severe JB, Calabrese JR. Lithium treatment moderate-dose use study (LiTMUS) for bipolar disorder: a randomized comparative effectiveness trial of optimized personalized treatment with and without lithium. Am J Psychiatry. 2013 Jan;170(1):102-10. doi: 10.1176/appi.ajp.2012.12060751.

    PMID: 23288387DERIVED

  • Sylvia LG, Reilly-Harrington NA, Leon AC, Kansky CI, Ketter TA, Calabrese JR, Thase ME, Bowden CL, Friedman ES, Ostacher MJ, Iosifescu DV, Severe J, Keyes M, Nierenberg AA. Methods to limit attrition in longitudinal comparative effectiveness trials: lessons from the Lithium Treatment - Moderate dose Use Study (LiTMUS) for bipolar disorder. Clin Trials. 2012 Feb;9(1):94-101. doi: 10.1177/1740774511427324. Epub 2011 Nov 10.

    PMID: 22076437DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Interventions

Lithium CarbonateLithium

Condition Hierarchy (Ancestors)

Bipolar and Related DisordersMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

CarbonatesAlkaliesInorganic ChemicalsCarbonic AcidCarbon Compounds, InorganicLithium CompoundsMetals, AlkaliElementsMetals, LightMetals

Results Point of Contact

Title
Dr. Andrew Nierenberg, Director of the Bipolar Trials Network
Organization
Bipolar Clinic and Research Program at
ANIERENBERG@PARTNERS.ORG
617-724-0837

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 24, 2008

First Posted

April 28, 2008

Study Start

April 1, 2008

Primary Completion

March 1, 2010

Study Completion

March 1, 2010

Last Updated

February 13, 2018

Results First Posted

June 28, 2013

Record last verified: 2010-07

Locations

US(6)