Clinical trial NCT01272531: Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder (PGBD)
Official title: Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder (PGBD)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bipolar Affective Disorder
Keywords: pharmacogenetics
bipolar disorders
affective disorders
mood disorders
pharmacologic actions
psychotropic drugs
antimanic agents
antidepressant agents
lithium
lithium carbonate
Lithobid
Eskalith
divalproex
divalproex sodium
Depakote
valproate
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2011-01-07
Enrollment: 560
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Inpatient and outpatients with bipolar affective disorder

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.

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.

Primary outcomes:
measure: Time to relapse
timeFrame: every 2 months for 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Halifax
country: Canada
facility: Dalhousie University
state: Nova Scotia
city: Bergen
country: Norway
facility: University of Bergen
Study officials:
affiliation: University of California, San Diego
name: John R Kelsoe, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.