Determinants in Antidepressant Outcomes
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||SERT Affinity Determinants in Antidepressant Outcomes|
|Study Start Date:||January 2004|
|Study Completion Date:||September 2005|
|Primary Completion Date:||September 2005 (Final data collection date for primary outcome measure)|
OBJECTIVE: The objective of this dose-ranging three-arm study of fluoxetine is to study the kinetics of the serotonin transporter in platelets and relate this to antidepressant response by comparing the manipulation of serotonin and platelet measure to standard treatment as it now exists.
RESEARCH PLAN: The project will examine two methods of dose adjustment of selective serotonin reuptake inhibitor (SSRI) treatment: The first method emulates the current standard clinical practice, i.e., titrating the dosage based upon the subject's current depression symptomatology (standard treatment arm). The second method utilizes the measurement of the Km to create a dosage tailored to the individual to approach the optimum treatment Kapp (biological treatment arm). Additionally, the placebo arm will control for treatment failure and high placebo response. This application is a double-blind, placebo controlled, randomized, dose ranging study in male and female outpatients with Major Depressive Disorder. The proposed study will take place over a period of 12 weeks recruiting 117 subjects (in order to achieve 90 completers, 30 in each arm, assuming 30% dropout rate) over a five year period who are diagnosed with Major Depression according to DSM-IV criteria. Following a 1 week screening period during which safety assessments are completed and evaluated and the Km and dosage are calculated, the subjects will be blindly randomized in a 1:1:1 ratio to either the standard treatment, the biological arm or the placebo arm. Subjects will return to the clinic at weeks 4, 8, and 12 for ratings and platelet Km determinations. Response will be measured and dosage adjustment will be made at weeks 4 and 8. A final determination of response will be made at week 12.
METHODS: Responders will be identified according to conventional criteria will be defined as those subject who 1) have a 50% or more improvement from baseline scores, as measured on the Hamilton Depression Scale (HAM-D), 2) no longer meet Major Depressive criteria according to DSM-IV; and 3) score < 10 on the HAM-D 17 item or <15 on the 24-item HAM-D. The efficacy measures will be the Hamilton Depression Scale (HAM-D): The seventeen item scale is designed to measure depression level; Montgomery-Asberg Depression Rating Scale (MADRS): A scale designed to provide additional subjective information to determine depressive symptoms; The Profile of Mood States (POMS) and the Cloninger Temperament Character Index (TCI) are patient rated scales which measure feelings and personality traits. The safety parameters include physical examinations, vital signs, collection of adverse events, and 12-lead electrocardiogram (ECG) and clinical laboratory assessments.
CLINICAL RELEVANCE: Previous studies have indicated fluoxetine is an effective treatment for depression. This study is designed to provide additional information concerning the methods for determining dose. Potentially, the information gained from this research may provide a more cost-effective way of finding an effective dose than the trial and error approach generally used.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00108316
|United States, Georgia|
|VA Medical Center, Augusta|
|Augusta, Georgia, United States, 30904|
|Principal Investigator:||Jeffrey Rausch, MD||VA Medical Center, Augusta|