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Cellular Aging and Neurobiology of Depression Study (CAN-D)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by University of California, San Francisco
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00285935
First received: January 31, 2006
Last updated: February 17, 2016
Last verified: February 2016
  Purpose

We are conducting an eight week longitudinal study to learn if blood levels of certain naturally occurring compounds and genetic markers differ between patients with depression and healthy adults who are not depressed, and if any such differences relate to memory performance, mood, and neurobiology.

We will do this by comparing the unmedicated depressed patients with matched healthy controls at baseline and then following the depressed patients over the course of eight weeks 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 ]
  • 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 ]

Estimated Enrollment: 228
Study Start Date: December 2010
Estimated Study Completion Date: February 2020
Estimated Primary Completion Date: February 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment with SSRI

Depressed participants will receive 8 weeks of treatment with one of the following serotonin-specific reuptake inhibitors:

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

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 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. If found to be eligible, participants would then be admitted to the study.

The next step for eligible, consenting depressed subjects and healthy controls is a baseline hospital visit and baseline MRI. The baseline hospital visit will last about 4 hours. We will begin the baseline visit by collecting a urine sample for a drug (and, for women, pregnancy) test. As long as that is negative, we will then collect a blood sample of about 135cc. After the blood draw, participants will complete cognitive tests and meet again with the study psychiatrist. Participants will also complete a baseline Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) of their brain at the Veteran's Affairs (VA) Hospital in San Francisco.

After the baseline hospital visit and MRI, depressed subjects (but not healthy controls) will begin taking an FDA approved antidepressant, as prescribed by the study psychiatrist, for the next 8 weeks while they are enrolled in the study. The specific drug will be decided upon between the participant and the study psychiatrist at the in-person screening visit.

After 4 weeks, depressed participants will return to UCSF to meet again with the psychiatrist to discuss symptoms and how to continue treatment; at that visit, they will have another blood draw of 135cc (the same blood draw as at baseline). Healthy controls will return at week 4 only for the blood draw.

4 weeks later (after 8 weeks in total), we will bring both depressed and healthy participants back for an additional visit that will include the same blood draw, testing, and MRI as the baseline visit. 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:   21 Years to 55 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

All participants must meet the following criteria:

  • Age 21-55 and able to give informed consent.
  • Not "needle phobic," by self-report.
  • English-speaking (to allow accurate use of 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).
  • Good general medical health; no significant uncontrolled illnesses.
  • 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 statins or medications that affect hormones [e.g. birth control pills or steroids]).
  • Free of all psychotropic medications (including antidepressants) for at least 6 weeks (with the exception of prn short-acting benzodiazepines or sedative-hypnotics, < 3 doses per week, and none for 5 drug half-lives before the study).
  • No vaccines for at least 4 weeks prior to baseline blood draw (including the flu shot).
  • Not currently anemic (Hct of 36-48 for females and 38-54 for males, or Hgb of 12.5-20) and has not donated blood for at least 8 weeks prior to baseline blood draw.
  • No MRI exclusions (e.g. severe claustrophobia, metal implants, pacemakers, BMI >38).
  • No neurological disorders and no history of concussion with a black-out that lasted > 10 minutes.

Additional criteria for Depressed Participants:

  • Current DSM-5 diagnosis of Major Depressive Disorder, unipolar, with non-psychotic features.
  • Baseline 17-item Hamilton Depression Rating Scale (HDRS) rating of > 17.
  • > 2.5 years since initial onset of depression and current depressive episode duration of > 6 weeks.
  • No current, active suicidal intent; HDRS "suicidality" item rating < 2 OR by clinician determination.
  • No recent (< 6 month) history of substance or alcohol use disorder(s), with the exception of tobacco use (DSM-5 criteria).
  • No current (in the last month) diagnosis of Post-Traumatic Stress Disorder (DSM-5 criteria).
  • No anticipated changes in psychotherapeutic interventions during the course of the study.

Additional criteria for Normal Controls:

• No history of DSM-5 Axis I diagnoses

  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
National Institutes of Health (NIH)
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Owen Wolkowitz, MD University of California, San Francisco
  More Information

Additional Information:
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  R01MH083784 
Study First Received: January 31, 2006
Last Updated: February 17, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Major Depressive Disorder
MDD
Neurobiology
Selective Serotonin Reuptake Inhibitor
SSRI
Depression

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Serotonin
Serotonin Uptake Inhibitors
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators

ClinicalTrials.gov processed this record on September 30, 2016