Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder (PGBD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2012 by University of California, San Diego
Sponsor:
Information provided by:
University of California, San Diego
ClinicalTrials.gov Identifier:
NCT01272531
First received: January 6, 2011
Last updated: April 9, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Bipolar Affective Disorder
Drug: Mood stabilizer treatment
Phase 4

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder (PGBD)

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Time to relapse [ Time Frame: every 2 months for 2 years ] [ Designated as safety issue: No ]

    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.


Biospecimen Retention:   Samples With DNA

DNA from patients with bipolar disorder


Estimated Enrollment: 880
Study Start Date: January 2011
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.
Drug: Mood stabilizer treatment
lithium or valproate
Other Names:
  • lithium carbonate
  • Eskalith
  • Lithobid
  • divalproex sodium
  • Depakote
  • Depakene
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.
Drug: Mood stabilizer treatment
lithium or valproate
Other Names:
  • lithium carbonate
  • Eskalith
  • Lithobid
  • divalproex sodium
  • Depakote
  • Depakene

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Inpatient and outpatients with bipolar affective disorder

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01272531

Contacts
Contact: Anna DeModena 858-642-3590 ademodena@ucsd.edu
Contact: Susan G Leckband, R.Ph. 858-552-8585 ext 5337 susan.leckband@va.gov

Locations
United States, California
University of California San Diego Recruiting
San Diego, California, United States, 92037
Contact: Anna DeModena    858-642-3590    ademodena@ucsd.edu   
Principal Investigator: John R. Kelsoe, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Ben Romanos    773-834-5128    bromanos@yoda.bsd.uchicago.edu   
Principal Investigator: Elliot Gershon, MD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Carrie Fisher, RN    317-274-8844    cfisher2@iupui.edu   
Principal Investigator: John Nurnberger, MD         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Bruce H Tarwater, MSW, LISW    319-353-5684    bruce-tarwater@uiowa.edu   
Principal Investigator: William Coryell, MD         
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Emma K Stokes, MHS    410-550-1652    estokes9@jhmi.edu   
Principal Investigator: Peter Zandi, PhD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109-2700
Contact: Gloria Harrington    877-864-3637    BPResearch@umich.edu   
Principal Investigator: Melvin McInnis, MD         
United States, Ohio
University Hospitals Case Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Carla Conroy    216-844-2871    Carla.Conroy@uhhospitals.org   
Principal Investigator: Joe Calabrese, MD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104-3309
Contact: Zachary Guy-Frank    215-746-6414    guyfrank@mail.med.upenn.edu   
Principal Investigator: Wade Berrettini, MD         
Canada, Nova Scotia
Dalhousie University Recruiting
Halifax, Nova Scotia, Canada, B3H 2E2
Contact: Julie Garnham, RN BN    (902) 473-7144    jgarnham@dal.ca   
Contact: Claire Slaney    (902) 473-5884    Claire.Slaney@cdha.nshealth.ca   
Principal Investigator: Martin Alda, MD         
Norway
University of Bergen Recruiting
Bergen, Norway, 5020
Contact: Petter Jakobsen    (+47) 55 95 84 67    , petter.jakobsen@helse-bergen.no   
Principal Investigator: Ketil J Oedegaard, MD, PhD         
Sponsors and Collaborators
University of California, San Diego
Investigators
Principal Investigator: John R Kelsoe, M.D. University of California, San Diego
  More Information

Additional Information:
No publications provided

Responsible Party: John R. Kelsoe, MD, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01272531     History of Changes
Other Study ID Numbers: NIH 1 U01 MH92758-01
Study First Received: January 6, 2011
Last Updated: April 9, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Diego:
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

Additional relevant MeSH terms:
Bipolar Disorder
Disease
Mood Disorders
Genetic Diseases, X-Linked
Affective Disorders, Psychotic
Mental Disorders
Pathologic Processes
Genetic Diseases, Inborn
Valproic Acid
Lithium Carbonate
Lithium
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Antidepressive Agents
Antipsychotic Agents

ClinicalTrials.gov processed this record on September 30, 2014