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Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder (PGBD)

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ClinicalTrials.gov Identifier: NCT01272531
Recruitment Status : Completed
First Posted : January 7, 2011
Last Update Posted : June 9, 2020
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
John Kelsoe, 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.

Condition or disease Intervention/treatment
Bipolar Affective Disorder Drug: Mood stabilizer treatment

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.

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Study Type : Observational
Actual Enrollment : 560 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder (PGBD)
Actual Study Start Date : April 2011
Actual Primary Completion Date : April 2016
Actual Study Completion Date : April 2016


Group/Cohort Intervention/treatment
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




Primary Outcome Measures :
  1. Time to relapse [ Time Frame: every 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.


Biospecimen Retention:   Samples With DNA
DNA from patients with bipolar disorder


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01272531


Locations
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United States, California
University of California San Diego
San Diego, California, United States, 92037
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109-2700
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-3309
Canada, Nova Scotia
Dalhousie University
Halifax, Nova Scotia, Canada, B3H 2E2
Norway
University of Bergen
Bergen, Norway, 5020
Sponsors and Collaborators
University of California, San Diego
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: John R Kelsoe, M.D. University of California, San Diego
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: John Kelsoe, Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01272531    
Other Study ID Numbers: NIH 1 U01 MH92758-01
U01MH092758 ( U.S. NIH Grant/Contract )
First Posted: January 7, 2011    Key Record Dates
Last Update Posted: June 9, 2020
Last Verified: June 2020
Keywords provided by John Kelsoe, 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:
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Disease
Bipolar Disorder
Mood Disorders
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Valproic Acid
Lithium Carbonate
Anticonvulsants
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