Functional and Neurochemical Correlates of Treatment Response in Major Depressive Disorder

August 10, 2013 updated by: Tara Lauriat, Mclean Hospital
This is an ancillary study to a clinical trial that is being conducted at Massachusetts General Hospital. Investigators at MGH are conducting a clinical trial to test the efficacy of ziprasidone together with escitalopram for treatment-resistant depression (NCT00633399). This observational study will involve magnetic resonance scans to examine brain chemistry (neurotransmitter levels), brain activity, and functional connections between brain regions before and after participating in the trial. The neurotransmitters of interest are glutamate, glutamine, and GABA. Comparisons will be made between individuals who receive ziprasidone and individuals who receive an inactive placebo. Differences between participants who respond to standard antidepressants and those who require additional medication will also be examined. All participants will have a baseline magnetic resonance scan before starting medication. The second scan will be after 8 weeks of escitalopram treatment for those who respond or following 8 weeks of escitalopram plus ziaprasidone or placebo (16 weeks after starting) for those who do not respond to escitalopram alone. Participants will complete standard rating scales for depression at each visit.

Study Overview

Status

Terminated

Conditions

Study Type

Observational

Enrollment (Actual)

1

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
    • Massachusetts
      • Belmont, Massachusetts, United States, 02478
        • McLean Hospital - McLean Imaging Center

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

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Participants in a clinical trial for treatment-resistant depression who agree to have magnetic resonance scans

Description

Inclusion Criteria:

  • Aged 18-65
  • Meets DSM-IV criteria for major depressive disorder
  • Meets eligibility criteria for clinical trial of ziprasidone augmentation of escitalopram
  • Capable of providing informed consent

Exclusion Criteria:

  • Meets exclusion criteria for augmentation clinical trial protocol
  • Pregnancy or unwillingness to avoid pregnancy during trial
  • Current or past psychosis or bipolar disorder
  • Substance abuse or dependence in the past six months
  • Clinically significant suicidality
  • Unstable cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizures
  • Use of a concomitant medication that acts on glutamate or GABA neurotransmission
  • Contraindication to magnetic resonance imaging (metal implant or device, occupational metal exposure, significant claustrophobia)

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

Cohorts and Interventions

Group / Cohort
escitalopram responders no augmentation
Participants who show a clinical response following 8 weeks on an SSRI will have a final magnetic resonance scan at the end of 8 weeks and will complete the study at that time.
Ziprasidone augmentation
Participants who do not respond to escitalopram and are randomized to ziprasidone augmentation will have a final magnetic resonance scan following 8 weeks on ziprasidone.
Placebo augmentation
Participants who do not respond to escitalopram and are randomized to placebo augmentation will have a final magnetic resonance scan following 8 weeks on placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glutamate level in antidepressant non-responders
Time Frame: 8 weeks after starting combination therapy phase
Glutamate levels are measured by magnetic resonance spectroscopy 8 weeks after starting treatment with ziprasidone or placebo in addition to escitalopram.
8 weeks after starting combination therapy phase

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glutamine level in treatment-responders following six weeks of antidepressant and non-responders following six weeks of adjunctive treatment.
Time Frame: 8 weeks or 16 weeks
8 weeks or 16 weeks
Glutamine level in treatment-responders following six weeks of antidepressant and non-responders following six weeks of adjunctive treatment
Time Frame: 8 weeks
8 weeks
GABA level in treatment-responders following six weeks of antidepressant and non-responders following six weeks of adjunctive treatment
Time Frame: 8 weeks
8 weeks
Glutamine level in antidepressant non-responders
Time Frame: 8 weeks
Glutamine levels are measured by magnetic resonance spectroscopy 6 weeks after starting treatment with ziprasidone or placebo together with escitalopram.
8 weeks
GABA level in antidepressant non-responders
Time Frame: 8 weeks
GABA levels are measured by magnetic resonance spectroscopy 6 weeks after starting treatment with ziprasidone or placebo together with escitalopram.
8 weeks
Functional connectivity in default mode network measured by functional magnetic resonance imaging (fMRI) in treatment-resistant individuals receiving adjunctive treatment
Time Frame: 8 weeks after starting combination therapy phase
Functional connectivity will be measured by performing fMRI in the resting state.
8 weeks after starting combination therapy phase
Functional connectivity in default mode network measured by functional magnetic resonance imaging (fMRI) in treatment-resistant individuals receiving adjunctive treatment and treatment-responders receiving an antidepressant
Time Frame: 8 weeks
8 weeks

Collaborators and Investigators

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

Sponsor

Mclean Hospital

Collaborators

Massachusetts General Hospital
Pfizer

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

July 1, 2012

Primary Completion (Actual)

April 1, 2013

Study Registration Dates

First Submitted

May 9, 2012

First Submitted That Met QC Criteria

May 12, 2012

First Posted (Estimate)

May 15, 2012

Study Record Updates

Last Update Posted (Estimate)

August 13, 2013

Last Update Submitted That Met QC Criteria

August 10, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • WS2058787

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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