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Imaging Predictors of Treatment Response in Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00367341
Recruitment Status : Completed
First Posted : August 22, 2006
Results First Posted : January 9, 2014
Last Update Posted : January 9, 2014
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Helen Mayberg, Emory University

Tracking Information
First Submitted Date  ICMJE August 18, 2006
First Posted Date  ICMJE August 22, 2006
Results First Submitted Date  ICMJE November 21, 2013
Results First Posted Date  ICMJE January 9, 2014
Last Update Posted Date January 9, 2014
Study Start Date  ICMJE August 2006
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2013)
Remission Defined as Hamilton Depression Rating Scale-17 Score of Less Than or Equal to 7 at 12 Weeks [ Time Frame: Measured at week 12 ]
# of study participants with Hamilton Depression-17-item score less than or equal to 7.
Original Primary Outcome Measures  ICMJE
 (submitted: August 18, 2006)
Remission Defined as Hamilton Depression Rating Scale-17 Score of Less Than or Equal to 7 at 12 Weeks
Change History Complete list of historical versions of study NCT00367341 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2013)
Response Defined as 50% Change in Hamilton Depression Rating Scale-17 Score at 12 Weeks [ Time Frame: Measured at week 12. ]
Number of participants with a 50% change from Baseline on the Hamilton Depression Rating Scale-17-item score
Original Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2006)
Response Defined as 50% Change in Hamilton Depression Rating Scale-17 Score at 12 Weeks
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Imaging Predictors of Treatment Response in Depression
Official Title  ICMJE Imaging Predictors of Treatment Response in Depression
Brief Summary While there are many effective options for treating a major depressive episode, there are no clinical markers that predict the likelihood of remission with an initial trial of either an antidepressant medication or psychotherapy. More critically, there are also no reliable predictors that might anticipate failure to such standard treatments either alone or in combination. This project will characterize imaging-based brain subtypes that distinguish groups of depressed patients who later remit or not to SSRI pharmacotherapy or cognitive behavior therapy (CBT), respectively. To define these subtypes, a prospectively-treated cohort of 100 patients will be randomized to receive either escitalopram (s-CIT) or CBT for the first 12 weeks, with non-remitters to either first treatment crossed over to receive an additional 12 weeks of treatment with combined treatment. Non-remitters to both treatments will thus define a relatively treatment resistant third subgroup. Resting-state 18F-fluoro-deoxyglucose (FDG) positron emission tomography (PET) scans will be acquired prior to initiating antidepressant therapy, with pre-treatment scan patterns associated with three possible outcomes (CBT remission, s-CIT remission, and non-remission to both) assessed using multivariate analytic methods. A second PET scan, acquired early in the treatment course, will be used to assess the likelihood of response to the specific treatment first assigned. The proposed studies are a first step towards defining brain-based biomarkers predictive of differential treatment outcome in major depression; most critically, patterns distinguishing patients at risk for treatment resistance. Identification of such biomarkers has additional implications for future testing of novel therapies in patients with distinct brain signatures, including development of evidence-based treatment algorithms for individual patients.
Detailed Description

SPECIFIC AIMS Aim 1. To define baseline regional glucose metabolic patterns (measured using FDG PET) associated with differential clinical remission to each of two well-established, randomly delivered first-line antidepressant treatments—the SSRI escitalopram (s-CIT) or cognitive behavioral therapy (CBT) with cross-over treatment for non-remitters (sequential course of treatment model).

Aim 2. To define metabolic change patterns, occurring early in the course of both s-CIT and CBT, associated with successful and unsuccessful clinical remission to each intervention.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE
  • Drug: escitalopram
    Participants will receive treatment with escitalopram for 12 weeks.
    Other Name: Lexapro
  • Behavioral: Cognitive Behavioral Therapy (CBT)
    CBT will include 16 1 hour sessions provided over 12 weeks.
    Other Name: Talk Therapy
Study Arms  ICMJE
  • Escitalopram
    Intervention: Drug: escitalopram
  • Cognitive Behavioral Therapy
    Intervention: Behavioral: Cognitive Behavioral Therapy (CBT)
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 21, 2013)
Original Enrollment  ICMJE
 (submitted: August 18, 2006)
Actual Study Completion Date  ICMJE July 2013
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female patients between the ages of 18 and 60. (no subjects with first episode over age 50. This is an attempt to exclude patients with 'vascular depression' who have a potentially different pathophysiology and treatment response compared to idiopathic MDD.
  • DSM-IV criteria for unipolar Major Depressive Disorder.
  • HAM-D (24 item) score >/= 18 at Screening, >/= 15 at Baseline.
  • Co-morbid conditions (other than those listed under exclusion criteria below) will be accepted as long as MDD is the primary diagnosis (based on predominance and sequential development of symptoms).
  • Acceptable method of birth control (oral contraceptives, Depo-Provera, Norplant, condoms with spermicide. A vasectomy is acceptable in the framework of a stable monogamous relationship. Sexually inactive women must agree to contraception if they become sexually active during the study.
  • Educational level, degree of understanding and reliability so that participation is feasible.
  • Informed consent to participate and comply in the study.

Exclusion Criteria:

  • Known neurological disorders or documented head injury.
  • Serious and unstable medical illnesses including diabetes, cardiovascular disease and cancer.
  • Medical conditions with known mood changes (endocrine, autoimmune disorders)
  • Co-morbid DSM-IV Axis I Diagnoses

    1. Lifetime history of Bipolar Disorder, Schizophrenia, and other Psychotic Disorders, or Obsessive Compulsive Disorder
    2. Alcohol abuse or dependence within the past six months, psychoactive substance abuse or dependence within the past six months.
    3. Clinical evidence of a severe Personality Disorder that would impede participation or completion of a controlled trial.
  • ECT within the past 6 months.
  • Previous failure to achieve a much improved status on CGI-Improvement (the equivalent of >50% symptom reduction) with a course of CBT (defined as a minimum of 8 sessions during 8 weeks of a specified manual-driven therapy by a CBT trained therapist) or escitalopram (defined as a minimum of 6 weeks with the dose of 10 mgs achieved for at least 2 weeks)
  • Use of concomitant medications with the exception of:

    1. Maintenance/prophylactic meds for stable medical conditions
    2. Ambien 5-10 mgs may be prescribed for occasional use (up to a single dose a week for insomnia, as long as it is not the night before a clinic visit, PET/fMRI study or ratings.
    3. Antidepressants will be discontinued for 7 days prior to the screening visit, which will be a minimum of a week before the baseline scan (5 weeks for fluoxetine, protryptyline).
  • Current treatment with weekly individual or group psychotherapy targeted at the depressive symptoms, including psychodynamic, interpersonal or cognitive-behavioral.
  • Currently responding to medication treatment, without clinical reasons to change (e.g. side effects). Will not enroll a subject who wishes to discontinue an effective treatment for the sake of participation in the research.
  • Woman who are pregnant, breast feeding or intending to become pregnant during the course of the study.
  • Contraindications for MRI: pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, or other implants.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00367341
Other Study ID Numbers  ICMJE IRB00026176
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Helen Mayberg, Emory University
Study Sponsor  ICMJE Emory University
Collaborators  ICMJE National Institute of Mental Health (NIMH)
Investigators  ICMJE
Principal Investigator: Helen Mayberg, M.D. Emory University
PRS Account Emory University
Verification Date November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP