Brain, Biology and Mood Study
The purpose of the Brain, Biology and Mood study is to examine the association between stress, depression and cell death in the hippocampus. We fully expect this study to highlight components of a "stress vulnerability pathway" that will be amenable to new pharmaceutical development and to improved diagnostic methods for patients with major depression. The centerpiece of this program is a prospective study comparing unmedicated depressed patients with matched healthy controls at baseline and then following the depressed patients over the course of several months of standardized antidepressant treatment to gauge which baseline abnormalities normalize over the course of treatment.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Neurosteroid Metabolism and the Antidepressant Effects of Serotonin Specific Reuptake Inhibitors (SSRI's)|
- Depression ratings at baseline and 8 weeks [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: No ]
- Anxiety ratings at baseline and 8 weeks [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: No ]
- Serum levels of steroids and neurosteroids at baseline and 8 weeks [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: No ]
- Serum levels of oxidative stress markers at baseline and 8 weeks [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: No ]
- Serum levels of cytokines and immune markers at baseline and 8 weeks [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: No ]
- Peripheral blood mononuclear cell telomere length and telomerase levels at baseline, and telomerase at 8 weeks [ Time Frame: baseline and 8 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||December 2010|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Drug: Sertraline (drug)
Following an initial telephone screen to assess inclusion and exclusion criteria, the evaluation will continue with an in-person evaluation to assess the presence or absence of active medical history and history of major psychiatric illness, as well as review of the consent document. Eligible, consenting healthy control and depressed subjects will complete a urine screening test for drugs of abuse (and pregnancy for women of child-bearing capacity), psychological tests measuring mood and memory, have a blood draw of approximately 190 cc, and be given materials and instructions for home saliva and urine collection. Subjects will then have a baseline brain MRI and MRSI scan to assess hippocampal and other regional brain volumes, perfusion and chemical profiles. This will be the end of the study procedure for the healthy controls. Depressed subjects, but not the healthy controls, will then receive an 8-week open label treatment with sertraline, during which time additional repeat behavioral evaluations will be performed at Weeks 4 and 8. To minimize the burden of a large volume of blood collection, a repeat full biochemical evaluation (identical to baseline) will be performed at Week 8, and reduced biochemical evaluations will take place at Week 4. Flow charts for the study procedures are provided in Tables 1 and 2 in the Appendix.
We have elected to use an open-label design for the antidepressant treatment phase of our study, instead of a double-blind-placebo controlled one, since: (a) there are some ethical concerns involved in treating actively depressed patients with placebo medication for extended periods of time, (b) recruitment of subjects into this study will be greatly enhanced if all subjects know they will receive an active antidepressant drug, and (c) our goal is to assess whether measurement of these factors provides clinically useful information in clinical settings as predictors of later clinical response (rather than having as a goal the demonstration of the clinical efficacy of sertraline).
The following is a description of the antidepressant treatment phase for the depressed subjects: Depressed subjects will begin an 8-week open-label outpatient study assessing the neuroendocrine, antidepressant and anti-anxiety effects of the SSRI sertraline. Patients will be started at an oral dose of sertraline of 25 mg. per day, and the dose will be titrated upwards by a treating physician according to standard clinical ("treatment as usual") guidelines and no more rapidly than the manufacturer's package insert guidelines up to a maximum dose of 200 mg. per day. The maximum dose will be determined clinically, based on response and tolerability. Treatment will be continued for 8 weeks, unless the subject wishes to stop treatment earlier, the clinician determines it to be in the subject's best interest to stop treatment earlier, or the subject meets certain discontinuation criteria detailed below. Behavioral, biological and physiological assessments (described below) will be performed at baseline and at the end of weeks 4 and 8. At baseline, patients will have MRI and MRSI scans. In between these primary assessment points, depressed subjects will have scheduled clinical evaluations (without any specific study-related biological and physiological testing and with limited formal behavioral ratings, described below) after 1, 2 and 3 weeks of starting sertraline and thereafter according to clinicians' judgment and clinical need, to monitor clinical response and safety.
After the end of the study, a physician-investigator will meet with the depressed subjects to review their clinical responses to sertraline and to make treatment suggestions, which the subjects may use in discussions of their future treatment options with their personal physicians. If a decision is made to discontinue sertraline, the subjects will be given instructions on how to withdraw from this medication, and will be given up to a 2 week supply of sertraline to facilitate this withdrawal.
|Contact: Owen Wolkowitz, MD||415-476-7433||Owen.Wolkowitz@ucsf.edu|
|United States, California|
|University of California San Francisco||Recruiting|
|San Francisco, California, United States, 94143-0984|
|Contact: Owen Wolkowitz, MD 415-476-7433 Owen.Wolkowitz@ucsf.edu|
|Principal Investigator:||Owen Wolkowitz, MD||University of California, San Francisco|