Imaging Predictors of Treatment Response in Depression

November 21, 2013 updated by: Helen Mayberg, Emory University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
82

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Escitalopram
Drug: escitalopram
Participants will receive treatment with escitalopram for 12 weeks.
Other Names:
  • Lexapro
Other: Cognitive Behavioral Therapy
Behavioral: Cognitive Behavioral Therapy (CBT)
CBT will include 16 1 hour sessions provided over 12 weeks.
Other Names:
  • Talk Therapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Measured at week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Measured at week 12.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Emory University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Mental Health (NIMH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Helen Mayberg, M.D., Emory University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 18, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2006

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 22, 2006

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 9, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 21, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00026176

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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