Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder (PGBD)

NCT ID: NCT01272531

Last Updated: 2020-06-09

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 560 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2016-04-30

Brief Summary

This is a prospective pharmacogenomics study of mood stabilizer response. The goal of this work is to identify genes associated with good response of patients with bipolar disorder to two commonly used mood stabilizing agents, lithium and valproate.

Detailed Description

All subjects meeting study inclusion criteria will be started on lithium. Those that fail lithium will be crossed over to valproate (VPA). Those that also fail VPA will be again crossed-over to a standardized treatment as usual (TAU) arm. Subjects who are eligible for the study must be at least 18 years of age and have been diagnosed or are thought to have bipolar I disorder with at least one episode of mood instability in the last 12 months. They must also be eligible to take lithium and, if female and of child bearing age, agree to use adequate birth control methods and to inform their doctor of their plans to become pregnant.

Conditions

Bipolar Affective Disorder

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

lithium

All study subjects will be started on lithium and taken off other medications, such as antidepressants, antipsychotic or other mood stabilizers used to control their mood. They will be stabilized over a 3 month time period, observed for one month, the followed every 2 months for 2 years.

Mood stabilizer treatment

Intervention Type: DRUG

lithium or valproate

valproate

Subjects that do not achieve stabilization or relapse while on lithium monotherapy will be started on valproate (VPA), in an identically designed prospective trial of VPA.

Mood stabilizer treatment

Intervention Type: DRUG

lithium or valproate

Interventions

Mood stabilizer treatment

lithium or valproate

Intervention Type: DRUG

Other Intervention Names

lithium carbonate; Eskalith; Lithobid; divalproex sodium; Depakote; Depakene

Eligibility Criteria

Inclusion Criteria

• Any phase of bipolar I disorder including, depressive, manic, hypomanic, mixed, or baseline/euthymic/not symptomatic;
• Lithium naïve patients and inadequately past lithium treated patients will be required to have had at least one affective episode in the last 12 months meeting DSM-IV criteria. Current lithium treated patients (CLTPs) will be stable on lithium monotherapy and will be exempted from this criterion if they have had no mood episodes meeting DSM-IV criteria in the last 6 months;
• Both outpatients and inpatients will be permitted to enroll into this study;
• Able to give informed consent, in the judgment of the investigator;
• Age greater than or equal to 18 years;
• Women of child bearing potential agree to inform their doctor at the earliest possible time of their plans to conceive, and to use adequate contraception (e.g. oral contraceptives, intrauterine device, barrier methods, or total abstinence from intercourse), and to understand the risks of lithium to the fetus and infant. Depo Provera is acceptable if it is started 3 months prior to enrollment.

Exclusion Criteria

• Unwilling or unable to comply with study requirements;
• Renal impairment (serum creatinine >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;
• Other contraindication to lithium;
• Currently in crisis such that inpatient hospitalization or other crisis management should take priority;
• Subjects with alcohol/drug dependence who meet criteria for physical dependence requiring acute detoxification;
• Pregnant or breastfeeding;
• Women of child-bearing potential who aren't able to agree to the requirements specified above;
• Those who have participated in a clinical trial of an investigational drug within the past 1 month;
• Inability to agree to comply with the visit schedule or study procedures;
• History of lithium toxicity, not due to mismanagement or overdose that required treatment;
• Current unstable medical condition.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

John Kelsoe

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John R Kelsoe, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

University of California San Diego

San Diego, California, United States

University of Chicago

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

University of Iowa

Iowa City, Iowa, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

University Hospitals Case Medical Center

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Dalhousie University

Halifax, Nova Scotia, Canada

University of Bergen

Bergen, , Norway

Countries

United States; Canada; Norway

References

Oedegaard KJ, Alda M, Anand A, Andreassen OA, Balaraman Y, Berrettini WH, Bhattacharjee A, Brennand KJ, Burdick KE, Calabrese JR, Calkin CV, Claasen A, Coryell WH, Craig D, DeModena A, Frye M, Gage FH, Gao K, Garnham J, Gershon E, Jakobsen P, Leckband SG, McCarthy MJ, McInnis MG, Maihofer AX, Mertens J, Morken G, Nievergelt CM, Nurnberger J, Pham S, Schoeyen H, Shekhtman T, Shilling PD, Szelinger S, Tarwater B, Yao J, Zandi PP, Kelsoe JR. The Pharmacogenomics of Bipolar Disorder study (PGBD): identification of genes for lithium response in a prospective sample. BMC Psychiatry. 2016 May 5;16:129. doi: 10.1186/s12888-016-0732-x.

Reference Type: DERIVED

PMID: 27150464 (View on PubMed)

Related Links

http://www.lithium.ucsd.edu

PGBD website

Other Identifiers

U01MH092758

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIH 1 U01 MH92758-01

Identifier Type: -

Identifier Source: org_study_id