NCT01272531

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
560

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Apr 2011

Longer than P75 for all trials

Geographic Reach
3 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 6, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 7, 2011

Completed
3 months until next milestone

Study Start

First participant enrolled

April 1, 2011

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

June 9, 2020

Status Verified

June 1, 2020

Enrollment Period

5 years

First QC Date

January 6, 2011

Last Update Submit

June 4, 2020

Conditions

Bipolar Affective Disorder

Keywords

pharmacogeneticsbipolar disordersaffective disordersmood disorderspharmacologic actionspsychotropic drugsantimanic agentsantidepressant agentslithiumlithium carbonateLithobidEskalithdivalproexdivalproex sodiumDepakotevalproate

Outcome Measures

Primary Outcomes (1)

  • Time to relapse

    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.

    every 2 months for 2 years

Study Arms (2)

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

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

Interventions

Mood stabilizer treatmentDRUG

lithium or valproate

Also known as: lithium carbonate, Eskalith, Lithobid, divalproex sodium, Depakote, Depakene
lithiumvalproate

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

Inpatient and outpatients with bipolar affective disorder

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

University of California San Diego

San Diego, California, 92037, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-2700, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104-3309, United States

Location

Dalhousie University

Halifax, Nova Scotia, B3H 2E2, Canada

Location

University of Bergen

Bergen, 5020, Norway

Location

Related Publications (1)

  • 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.

    PMID: 27150464DERIVED

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

DNA from patients with bipolar disorder

MeSH Terms

Conditions

Bipolar DisorderMood Disorders

Interventions

Lithium CarbonateValproic Acid

Condition Hierarchy (Ancestors)

Bipolar and Related DisordersMental Disorders

Intervention Hierarchy (Ancestors)

CarbonatesAlkaliesInorganic ChemicalsCarbonic AcidCarbon Compounds, InorganicLithium CompoundsPentanoic AcidsValeratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty Acids, VolatileFatty AcidsLipids

Study Officials

  • John R Kelsoe, M.D.

    University of California, San Diego

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

January 6, 2011

First Posted

January 7, 2011

Study Start

April 1, 2011

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

June 9, 2020

Record last verified: 2020-06

Locations

NO(1)US(8)CA(1)