16-week Comparative Effectiveness Trial of Lamotrigine vs. Fluoxetine for Bipolar Depression (FLAME)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||16-week Open Randomized Comparative Effectiveness Trial of Lamotrigine vs. Fluoxetine for Bipolar Depression: Pharmacogenomic and Biomarker Predictors of Response|
- Inventory for Depressive Symptoms [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||March 2015|
|Estimated Study Completion Date:||April 2018|
|Estimated Primary Completion Date:||January 2018 (Final data collection date for primary outcome measure)|
Active Comparator: Lamotrigine
Subjects on this arm will be randomized to Lamotrigine.
Lamotrigine dosing: 25 mg daily x 2 weeks, 50 mg daily x 2 weeks, 100 mg daily x 2 weeks, 200 mg (100 mg bid)) x 4 weeks. If patient still has at least mild depressive symptoms, the dose can be increased to 300 mg daily for 2 weeks and 400 mg for 4 weeks. Dose will be held for treatment response and can be reduced for side effects.
Other Name: Lamictal
Active Comparator: Fluoxetine
Subjects on this arm will be randomized to Fluoxetine.
Fluoxetine dosing: 20mg for month 1, 40mg for month 2, and if still depressed (CGI ≥ 3) 60mg for month 3 and 4. Lower doses of fluoxetine will be prescribed for those with side effects. For known Cytochrome P450 2D6 poor metabolizers, fluoxetine will not be dosed > 40mg.
Other Name: Prozac
Depression is the predominant prevailing mood state of bipolar disorder and it is associated with substantial morbidity and mortality. However, in comparison to acute mania, bipolar depression is understudied both from the standpoint of its pathophysiology as well as clinical trials and treatment development. Given the lack of evidence-based guidelines, clinicians and participants enter a treatment phase with little guidance.
The FLAME Study is a 16-week, open randomized comparative effectiveness trial evaluating genomic predictors and biomarkers of response and adverse events to treatment with lamotrigine (n=200) and fluoxetine (n=200) for bipolar I, II and bipolar schizoaffective depressed adults (18-65). Participants will be recruited over a 5-year period.
It is known that functionally significant genetic polymorphisms of pharmacokinetics and pharmacodynamic pathways can influence individual differences in repose to specific medications. We propose to evaluate the contribution of these pharmacogenomic variations to lamotrigine and fluoxetine treatment response and adverse events. We will correlate clinical phenotypes of response and adverse events to treatment with genotype and haplotype variations of drug metabolism, neurotransmitter biosynthesis, (metabolism, storage, release, reuptake), receptor and intracellular signaling-that have been previously implicated to either lamotrigine or fluoxetine. These initial steps will be complemented with genome-wide analysis (GWA), pathway analysis and other candidate gene studies.
Based on our results we aim to develop a translational treatment algorithm of bipolar depression that may help individualized treatment for bipolar depression. This algorithm for participants could potentially increase the likelihood of successful treatment interventions, deliver the "right treatment, for the right participant at the right time", and decrease the number of ineffective treatments and/or risk for serious adverse events.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02389712
|Contact: Autumn Timm||Timm.Autumn@mayo.edu|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Autumn Timm Timm.Autumn@mayo.edu|
|Principal Investigator:||Mark A Frye, MD||Mayo Clinic|