The goal of this work is to identify genes associated with good response of bipolar patients to two commonly used mood stabilizing agents, lithium and valproate. 1. All patients will be started on lithium, then enter the maintenance phase where they will be followed for 2 years or until relapse. Those that fail lithium will be crossed over to valproic acid (VPA). Those that fail on VPA will be again crossed-over to a standardized treatment as usual (TAU) arm. MedDRA version: 14.0 Level: LLT Cla
Conditions
Interventions
Trade Name: Lithionit
Product Name: Lithium
Product Code: no
Pharmaceutical Form: Tablet
INN or Proposed INN: Lithionit
CAS Number: 7439-93-2
Other descriptive name: LITHIUM
Trade Name: Orfiril
Produ
Sponsors
Haukeland University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1) Any phase of bipolar I disorder including, depressive, manic, hypomanic, mixed, or baseline/euthymic/not symptomatic, 2) 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, 3) Both outpatients and inpatients will be permitted to enroll into this study, 4) Able to give informed consent, in the judgment of the investigator; 5) Age greater than or equal to 18 years; 6) 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; Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria: 1) Unwilling or unable to comply with study requirements; 2) Renal impairment (serum creatinine >1.5 mg/dL); 3) 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; 4) Other contraindication to lithium, 5) Currently in crisis such that inpatient hospitalization or other crisis management should take priority; 6) Subjects with alcohol/drug dependence who meet criteria for physical dependence requiring acute detoxification 7) Pregnant or breastfeeding; 8) Women of child-bearing potential who aren’t able to agree to the requirements specified above; 9) Those who have participated in a clinical trial of an investigational drug within the past 1 month; 10) Inability to agree to comply with the visit schedule or study procedures; 11) History of lithium toxicity, not due to mismanagement or overdose that required treatment. 12) Current unstable medical condition.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.The study will have an algorithmic design. All patients will be started on lithium. Those that fail lithium will be crossed over to valproic acid (VPA). Those that fail that VPA will be again crossed-over to a standardized treatment as usual (TAU) arm. 2.The study will be designed to identify genes for relapse prevention. All patients will be stabilized on lithium monotherapy and then enter the maintenance phase where they will be followed for 2 years or until relapse. On relapse, they are discontinued or crossed over as appropriate. 3.All subjects will be genotyped at 1M single nucleotide polymorphism (SNP) DNA markers for a genomewide association study. The primary outcome measure will be time to relapse. Response and genotype data will be analyzed using survival analysis in order to identify genes whose alleles are associated with longer time to relapse. ;Secondary Objective: Secondary outcomes include studies of sub-phenotypes, co-morbidity and neuropsychological data.;Primary end point(s): Relapse is the primary outcome measure for the study, so its definition and assessment is key. Subjects whose rating scales suggest a relapse will be reviewed using the Mood Episode Checklist that summarizes DSM IV criteria for mania and depression. Relapse will be defined by the following criteria: 1) meets criteria for mania; 2) meets criteria for major depression; 3) meets criteria for a mixed episode. | — |
Countries
Norway
Outcome results
None listed