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Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder (PGBD)

Completed
Conditions
Bipolar Affective Disorder
Interventions
Drug: Mood stabilizer treatment
Registration Number
NCT01272531
Lead Sponsor
University of California, San Diego
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
560
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.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
lithiumMood stabilizer treatmentAll 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.
valproateMood stabilizer treatmentSubjects 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.
Primary Outcome Measures
NameTimeMethod
Time to relapseevery 2 months for 2 years

Relapse definition:

* meets criteria for mania and is considered "markedly ill" or worse; or

* meets criteria for major depression with 4 week duration;

* meets criteria for a mixed episode and is considered "markedly ill" or worse.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (10)

University of Iowa

🇺🇸

Iowa City, Iowa, United States

University Hospitals Case Medical Center

🇺🇸

Cleveland, Ohio, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

University of California San Diego

🇺🇸

San Diego, California, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

Johns Hopkins Hospital

🇺🇸

Baltimore, Maryland, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

University of Bergen

🇳🇴

Bergen, Norway

Dalhousie University

🇨🇦

Halifax, Nova Scotia, Canada

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