Brain, Biology and Mood Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of California, San Francisco
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00285935
First received: January 31, 2006
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: Treatment with SSRI
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Health Services Research
Official Title: Neurosteroid Metabolism and the Antidepressant Effects of Serotonin Specific Reuptake Inhibitors (SSRI's)

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Depression ratings at baseline and Week 8 [ Time Frame: baseline and Week 8 ] [ Designated as safety issue: No ]
  • Anxiety ratings at baseline and Week 8 [ Time Frame: baseline and Week 8 ] [ Designated as safety issue: No ]
  • Serum levels of steroids and neurosteroids at baseline and Week 8 [ Time Frame: baseline and Week 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum levels of oxidative stress markers at baseline and Week 8 [ Time Frame: baseline and Week 8 ] [ Designated as safety issue: No ]
  • Serum levels of cytokines and immune markers at baseline and Week 8 [ Time Frame: baseline and Week 8 ] [ Designated as safety issue: No ]
  • Peripheral blood mononuclear cell telomere length and telomerase levels at baseline [ Time Frame: baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 164
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)
Arms Assigned Interventions
Experimental: Treatment with SSRI

Depressed participants will be given the option of receiving 8 weeks of treatment with one of the following serotonin-specific reuptake inhibitors:

fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), escitalopram (Lexapro®)

The treatment arm of the study is completely optional. The specific drug used for treatment will be selected by the study clinician based on clinical interviews and the participants preferences. Participants will be monitored for response and side effects by study clinician and will return after 8 weeks for a follow up study visit.

Drug: Treatment with SSRI

Participants who choose to enroll in this phase are treated with an FDA-approved SSRI in an open-label "treatment-as-usual" manner, in accordance with clinical practices and at a titration rate no more rapid than the manufacturer's recommendations. The duration of the treatment phase is 8 weeks.

Other Name: fluoxetine (Prozac®), Sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), escitalopram (Lexapro®)


Detailed Description:

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. This will be the end of the study procedure for the healthy controls. Depressed subjects, but not the healthy controls, will then have the option of receiving an 8-week open label treatment with an FDA-approved antidepressant (to be decided upon between the subject and study psychiatrist). Additional repeat behavioral evaluations and a repeat full biochemical evaluation (identical to baseline) will be performed at Week 8.

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 FDA-approved antidepressants).

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 antidepressant treatment. Participants will be treated with an FDA-approved SSRI antidepressant under the supervision of a study psychiatrist. 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 week 8. 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 treatment 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 treatment and to make further 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 antidepressant treatment, the subjects will be given instructions on how to withdraw from the medication, and will be given up to a 4 week supply of the drug to facilitate this withdrawal.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • English speaking (to allow accurate use of the behavioral rating scales and verbal cognitive tests)
  • Females of child-bearing capacity must be non-pregnant (confirmed by urine pregnancy test) and using effective non-hormonal birth control (e.g. abstinence, condoms, IUD)
  • Age 18-70 y.o.
  • Good general medical health; no active significant uncontrolled medical illness.
  • Clinical labs (electrolytes, liver function test, CBC) with no clinically significant abnormalities
  • Negative urine toxicology (drugs of abuse) screen.
  • Taking no medication or drugs likely to interfere with the study objectives (including birth control pills and corticosteroids), except as allowed by protocol
  • Free of any antidepressant, mood-stabilizing or anti-anxiety medication for a minimum of 6 weeks before entry into the study (with the exception of prn benzodiazepine, anxiolytic or sedative-hypnotic use, < 3 nights per week)
  • BMI ≤ 38 and able to fit comfortably in the MRI/MRSI scanner
  • Able to give informed consent
  • Current DSM-IV Axis I diagnosis of Major Depressive Disorder, unipolar, without psychotic features (co-morbid diagnoses of Panic, Generalized Anxiety Disorder, or Phobias are permitted).
  • Baseline 17-item Hamilton Depression Rating Scale (HDRS) rating of > 17
  • Baseline HDRS item #3 ("suicidality") rating of < 1, and clinician's determination of absence of active suicidal intent.
  • No anticipated changes in psychotherapeutic interventions during the course of the study.

Exclusion Criteria:

  • No recent (< 6 month) history of substance or alcohol abuse (DSM-IV criteria)
  • No current diagnosis of Post-Traumatic Stress Disorder
  • Not "needle phobic," by self-report
  • Not "claustrophobic" by self-report
  • No metal implants
  • No significant neurological diseases such as schizophrenia, mental retardation, and significant head injury
  • No electroconvulsive therapy (ECT) within the past 6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00285935

Contacts
Contact: Owen Wolkowitz, MD 415-476-7433 Owen.Wolkowitz@ucsf.edu

Locations
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   
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Owen Wolkowitz, MD University of California, San Francisco
  More Information

No publications provided by University of California, San Francisco

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00285935     History of Changes
Other Study ID Numbers: 10-00825
Study First Received: January 31, 2006
Last Updated: April 28, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms

ClinicalTrials.gov processed this record on July 31, 2014