A Pilot Study of Infliximab for Treatment Resistant Major Depression - Full Text View

Sponsored by:	Emory University
Information provided by:	Emory University
ClinicalTrials.gov Identifier:	NCT00463580

Purpose

This is a preliminary evaluation to explore whether the TNF-alpha antagonist infliximab holds promise as a therapeutic intervention for treatment resistant depression. Twenty subjects with treatment resistant depression will be randomized in a double-blind fashion to receive a single infusion of either infliximab (5 mg/kg) or placebo (normal saline). Subjects will be followed for 12 weeks post-infusion, with evaluations at weeks 1, 2, 3, 4, 6, 8 and 12. Subjects who do not respond to the initial infusion (response defined as >50% reduction in Hamilton Depression Rating Scale score at any assessment in 8 weeks following the infusion) will be blindly crossed over to receive whichever condition (infliximab or placebo) they did not receive in the initial infusion. Subjects who are crossed over will be followed an additional 12 weeks in a manner identical to the protocol for the first 12 weeks. The choice of a single infusion is based both upon our clinical experience that improvements in mood and energy occur rapidly and on trials suggesting that therapeutic effects on disease states directly related to inflammatory activity (i.e. skin condition in psoriasis), as well as improvements in mood and energy, are apparent within the first several weeks following an initial infusion. Our decision to wait 8 weeks prior to crossing-over in non-responders is based on evidence suggesting that a single infusion of infliximab can have long lasting effects on disease states for which it has FDA approval.

Hypothesis #1: A single infusion of infliximab will be superior to placebo (saline infusion) in reducing depressive symptoms as assessed by differences between groups in symptom score change on the 24-item Hamilton Depression Rating Scale (HDRS) as well as percentage of responders (30% and 50% decrease in HDRS)and remitters (HDRS less than or equal to 7 or a Clinical Global Impression Scale Score of 1).

Hypothesis #2: In subjects receiving infliximab, decreases in inflammatory indices during treatment will correlate with a decrease in depressive symptom scores as assessed by the HAM-D.

Condition	Intervention	Phase
Depression Major Depressive Disorder	Drug: infliximab (remicade)	Phase IV

MedlinePlus related topics: Depression

Drug Information available for: Infliximab Tumor Necrosis Factors

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	A Pilot Investigation of the Efficacy of the Tumor Necrosis Factor-Alpha Antagonist Infliximab in Treatment Resistant Depression

Further study details as provided by Emory University:

Primary Outcome Measures:

(Study Endpoint): Between-group differences (mean ±SD) at all post-infusion time points in Hamilton Depression Rating Scale (HDRS)scores.

Secondary Outcome Measures:

Between group difference in percentage of patients with a 30% and a 50% reduction in Hamilton Depression Rating Scale (HDRS) scores at any study point.
Between group difference in percentage of remitted patients during
treatment (HDRS ≤7 or CGI of 1).
Between group differences in self-reported depression scores
measured by the IDS—SR.
Between group differences in quality of life post-infusion quality of life
measured by the SF-36.

Estimated Enrollment:	20
Study Start Date:	January 2007
Estimated Study Completion Date:	April 2008

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Males or females ages 18-65. Must be able to read and understand English.
Currently meets DSM-IV criteria for a major depressive episode. (History of either unipolar major depression (depressive episodes only) or bipolar I disorder (history of manias and depressions) or bipolar II disorder (hypomanias and depressions), current episode depressed acceptable).
Must meet criteria for "treatment resistant" depression defined by failure to respond to, or intolerance of, at least 2 treatment trials (antidepressants or ECT) during the current episode.
All subjects will be fully ambulatory and in good medical health.
Are required to either be antidepressant free for 2 weeks prior to study entry (4 weeks for fluoxetine secondary to long half-life) or be on a fixed psychotropic medication regimen for at least 4 weeks. Subjects and their primary care providers must agree to continue their status (i.e. without antidepressant or on a fixed regimen) until the 12-week assessment is complete.
Pre-menopausal female subjects must not be pregnant and must be willing to use adequate contraception during the study period.
Subjects are required to have a plasma high-sensitivity C-reactive protein (CRP) of greater than 3.

Exclusion Criteria:

Current or history of psychotic symptoms.
Active suicidal ideation (defined as a score of ≥3 on HDRS suicide item).
Prior use of a TNF-alpha antagonist (i.e. etanercept, infliximab, adalimimub) and use of any other immunosuppressant agent (i.e. systemic corticosteroids or anti-proliferative agents such as methotrexate) within one year of study entry.
Current use of aspirin, non-steroidal anti-inflammatory agents (NSAIDs) or COX-2 inhibitors during the study. Acetaminophen will be allowed.
History of any of the following conditions: Congestive heart failure, abnormal electrocardiogram, malignancy, schizophrenia, neurological disease, auto-immune condition (e.g. rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, lupus), chronic infection (e.g. human immunodeficiency virus, hepatitis B or C), and hematologic, renal or hepatic abnormality.
Subjects will be excluded for a positive anti-double stranded DNA antibody test.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00463580

Contacts

Contact: Bobbi J. Woolwine, MSW	404-712-9620	bwoolwi@emory.edu
Contact: Talitha Michalow, BA	404-727-8229	tmichal@emory.edu

Locations

United States, Georgia
Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences	Recruiting
Atlanta, Georgia, United States, 30322
Sub-Investigator: Andrew H. Miller, MD
Sub-Investigator: Robin Rutherford, MD
Sub-Investigator: Paul E. Holtzheimer, MD
Sub-Investigator: Vanitha Bala, MD
Sub-Investigator: Bobbi Woolwine, MSW
Sub-Investigator: Oyetunde Alagbe, MD
Sub-Investigator: Monica Cowles, MD

Sponsors and Collaborators

Emory University

Investigators

Principal Investigator:

Charles Raison, MD

Emory University

More Information

Study ID Numbers:	198-2005
Study First Received:	April 19, 2007
Last Updated:	April 19, 2007
ClinicalTrials.gov Identifier:	NCT00463580
Health Authority:	United States: Institutional Review Board

Keywords provided by Emory University:

depression
TNF-alpha antagonist
infliximab
treatment resistant depression
major depressive disorder (MDD)

Study placed in the following topic categories:

Necrosis
Depression
Infliximab
Mental Disorders

Mood Disorders
Depressive Disorder, Major
Depressive Disorder
Behavioral Symptoms

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Therapeutic Uses
Gastrointestinal Agents

Antirheumatic Agents
Dermatologic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009