Glutamatergic and GABAergic Mediators of Antidepressant Response in Major Depression

NCT01557946 | Completed Phase 4 Results

• 1 other identifier: 2011-P-001192
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Primarily, this study seeks to evaluate whether citalopram treatment is associated with an increase in the Glutamine (Gln)/Glutamate (Glu) ratio in the anterior cingulate cortex (ACC) from baseline to day 3 of treatment. Additionally, this study would like to examine whether citalopram treatment is associated with an increase in the Gln/Glu ratio in the ACC from baseline to day 7 of treatment. In order to more fully examine baseline neurochemical and functional abnormalities in participants with MDD, we also seek to scan a group of age- and sex-matched non-depressed comparison individuals in order to perform between-group analyses of baseline neuroimaging measures.

Conditions

MDD; Citalopram; Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Mean Difference From Baseline to Day 3 in Glutamine/Glutamate (Gln/Glu) Ratio Within Depressed Group

  Estimated mean difference (day 3 minus baseline) in the glutamine/glutamate (Gln/Glu) ratio in the rostral anterior cingulate cortex as measured by proton magnetic resonance spectroscopy from baseline to day 3 of citalopram treatment within the depressed group. The change in metabolites from baseline to each time point was assessed by random regression analysis, adjusting for age and sex, using generalized estimating equations to account for the correlation of observations within individuals.

  Change from Baseline to Day 3

Secondary Outcomes (1)

• Mean Difference From Baseline to Day 7 in Glutamine/Glutamate (Gln/Glu) Ratio Within Depressed Group

  Change from baseline to day 7

Study Arms (2)

Major Depression

EXPERIMENTAL

Participants with major depressive disorder received citalopram 20-40 mg daily for 6 weeks. MRI scans were acquired at baseline and days 3, 7, and 42.

Drug: citalopram

Healthy Volunteers

NO INTERVENTION

Healthy volunteer participants did not receive citalopram and performed one MRI scan.

Interventions

citalopram DRUG

citalopram 20-40 mg daily

Also known as: Celexa

Major Depression

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female age ≥ 18 and ≤ 65
• Meets DSM-IV criteria for MDD
• Current score of ≥ 18 on the 21-item Hamilton Depression Rating Scale (HAM-D).

You may not qualify if:

• Unwillingness or inability to provide written informed consent.
• Current suicidal ideation
• Active psychotic symptoms
• Lifetime history of bipolar disorder, schizophrenia, or OCD
• Failed treatment with an adequate trial of ≥ 2 antidepressants during the current major depressive episode ("failure" will be defined as ≤ 50% subjective improvement, and an "adequate trial" will be defined as at least 4 weeks of treatment using at least the minimum dose of the antidepressant recommended by the manufacturer in product labeling)
• DSM-IV diagnosis of alcohol or substance dependence, with the exception of nicotine dependence, within three months prior to screening
• Any history of treatment with electroconvulsive therapy
• Positive urine toxicology screen for any drug of abuse or excluded medication at screening. Opiate pain medication being taken for a medical condition is exempt from needing a negative opiate screen.
• Clinically significant medical or neurologic disease, as judged by the principal investigator, which would increase the risk to the participant or interfere with interpretation of results
• Female participants with a positive urine pregnancy test at screening
• \. Pregnancy. Females of childbearing potential must be using an effective contraceptive method (e.g., abstinence, prescription oral contraceptives, contraceptive injections, double-barrier method, male partner sterilization).
• \. Any screening laboratory abnormality deemed clinically significant by the investigator 14. A QTc interval on screening ECG of ≥ 450 msec. 15. Use of any excluded medications (see Section 6.7 below) that cannot be discontinued during the screening phase 16. Previous failure to respond to treatment with citalopram that would, in the judgment of the investigator, constitute an adequate trial in MDD 17. Treatment with any investigational medications within 30 days prior to screening 18. Any contraindications to having an MRI scan, including cardiac pacemakers, metal vascular clips or stents, artificial heart valves, certain kinds of prostheses, brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings (wounded in military combat, sheetmetal workers, welders, and others), transdermal drug delivery systems, and certain tattoos with metallic ink 19. Left-handedness

Sponsors & Collaborators

• Mclean Hospital: lead

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Citalopram

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Modest sample size due to participant attrition and the cost and logistical challenges of the study design. Multiple comparisons, increasing the likelihood of type I errors. Open-label design which leaves open the possibility of a placebo effect.

Results Point of Contact

• Title: Dr. Brian Brennan, MD
• Organization: McLean Hospital, Biological Psychiatry Laboratory

bbrennan@partners.org

617-855-2911

Study Officials

• Brian P. Brennan, M.D.

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director of Translational Neuroscience Research

Model Details: Open-label administration of citalopram to participants with major depressive disorder. MRI scans performed at baseline and days 3, 7, and 42. An age- and gender-matched group of healthy volunteers did not receive citalopram and received on MRI scan to perform between-group baseline analyses.

Study Record Dates

• First Submitted: March 9, 2012
• First Posted: March 20, 2012
• Study Start: March 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: September 12, 2017
• Results First Posted: September 12, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)