A Study of Infliximab for Treatment Resistant Major Depression (Infliximab)

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: NCT00463580
Recruitment Status : Completed
First Posted : April 20, 2007
Results First Posted : May 12, 2014
Last Update Posted : March 29, 2018
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Andrew H Miller, Emory University

Brief Summary:

Major depression is increasingly recognized to be a chronic and highly recurrent condition, which results in significantly increased health problems. One possible mechanism that may contribute to treatment resistance is increased production and release of chemicals called proinflammatory cytokines in patients with major depression. These chemicals mediate the body's response to infectious agents like bacteria and have been shown to be increased by psychological stress. They produce the symptoms that we associate with being sick, including fever, malaise and changes in sleep and appetite. Several lines of evidence indicate that proinflammatory cytokines may contribute to the development of major depression and may thus represent a novel target for the pharmacological treatment of the disorder.

The TNF-alpha antagonist, Infliximab(Remicade®), is an infusion style drug approved by the FDA for the treatment of inflammatory conditions like Crohns disease and rheumatoid arthritis. We are conducting a study to see if the infliximab (Remicade®) is more effective than placebo in acutely reducing symptoms of depression in patients who have elevated proinflammatory markers and have not responded to, or been unable to tolerate, at least two previous treatments in the current depressive episode. Proinflammatory markers are measured by a simple blood test for C-Reactive Protein(CRP)levels in the body.

After appropriate screening to determine eligibility, 64 subjects with treatment resistant depression will be randomized to receive three infusions of either infliximab(Remicade®)or placebo(salt water) in the Emory Infliximab Infusion Center in the Division of Digestive Diseases, Emory University School of Medicine. Subjects will be followed for 12 weeks with evaluations at weeks 0 (baseline), 1, 2, 3, 4, 6, 8, 10 and 12. The first infliximab(Remicade®)infusion will occur at the first (Baseline) visit. The second infusion will occur at Study Week 2 (the third visit). The third infusion will occur at Study Week 6 (Visit 6). The choice of three infusions, and the infusion schedule, is based on current recommendations for the use of infliximab(Remicade®)in conditions for which it has received FDA approval. Subjects will be evaluated for twelve weeks by trained clinicians for changes in depression symptoms and improvements in quality of life. In addition, a physician will evaluate subjects each visit to make sure they are remaining healthy. Blood will be withdrawn at baseline prior to infusion and all subsequent visits to check labs for safety but also to evaluate potential relationships between changes in inflammatory activity and therapeutic response. After Study Week 12, participants will be monitored by phone, every 4 weeks during the 22-Week Post Study Follow-up Phase to assess physical and psychiatric symptoms in the period following the final infusion. At the baseline and Week 8 visits, subjects will be admitted to the Atlanta Clinical Translational Science Institute(ACTSI),a research unit in the Emory Hospital, for an extended evaluation. The purpose of coming to the ACTSI will be for researchers to evaluate whether treatment with infliximab improves endocrine function, inflammation, sleep and thinking abilities in people who are depressed. For all other visits (Week 1, 2, 4, 6, 10 and 12), participants will come for an office visit in the Winship Cancer Institute.

Condition or disease Intervention/treatment Phase
Depression Drug: infliximab (remicade) Drug: Placebo Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Evaluation of the Efficacy of the Tumor Necrosis Factor-alpha Antagonist Infliximab in Treatment Resistant Major Depression: Mechanisms and Mediators
Study Start Date : November 2008
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Infliximab

Arm Intervention/treatment
Experimental: infliximab (Remicade)
Drug: infliximab (remicade)
Three infusions across a 12 week period. (Baseline, week 2 and week 6)
Other Name: Remicade

Placebo Comparator: Placebo
Normal saline
Drug: Placebo
Placebo 3 infusions across a 12 week period (Baseline, Week#2 and Week#6)
Other Name: Normal saline

Primary Outcome Measures :
  1. (Study Endpoint): Mean (SD) Hamilton Depression Rating Scale 17-item (HAM-D-17) Scores at Baseline and Each Post Baseline Time Point. [ Time Frame: baseline and treatment weeks 1, 2, 4, 6, 8, 10 and 12 ]
    Hamilton Depression Rating Scale-17 item; Minimum score= 0 Maximum score= 54; Higher scores represent greater symptom severity

Secondary Outcome Measures :
  1. Number of Patients With a 50% Reduction in HDRS Scores at Any Study Point [ Time Frame: through study completion ]
  2. Between Group Difference in Percentage of Remitted Patients During Treatment (HDRS ≤7 or CGI of 1) [ Time Frame: through study completion ]
  3. Between Group Differences in Self-reported Depression Scores Measured by the IDS—SR [ Time Frame: through study completion ]
  4. The Correlation Coefficient Between Changes in HDRS Symptom Score(Measured Numerically and as the Ratio of Change Score to Baseline Score) and Changes in the Plasma Concentrations of TNF-alpha, IL-6 and CRP. [ Time Frame: through study completion ]
  5. Between-group Differences (Mean ±SD) in the Change of Cortisol and ACTH Slope, p.m. Cortisol, Diurnal Plasma Cytokine and Cytokine Receptor Concentrations and Sleep Efficiency Between Baseline and Study Week 8. [ Time Frame: Between baseline and study week 8. ]
  6. Correlation Coefficients Between Changes in HDRS Symptom Score and Changes in Diurnal Slope of Cortisol and ACTH, p.m. Cortisol Plasma Concentrations, Diurnal Plasma Concentrations of Inflammatory Cytokines and Their Receptors and Sleep Efficiency [ Time Frame: Measured numerically and as the ratio of change score to baseline score ]
  7. CRP, IL-6, TNF-alpha, TNFR 1 and 2 [ Time Frame: Baseline ]
    Investigate the effects of baseline CRP (and IL-6, TNF-alpha, TNFR 1 and 2) on reduction in depressive symptoms in patients in the two treatment groups.

Information from the National Library of Medicine

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Ages Eligible for Study:   25 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Males or females ages 25-60. Must be able to read and understand English.
  2. 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).
  3. 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.
  4. All subjects will be fully ambulatory and in good medical health.
  5. 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.
  6. Pre-menopausal female subjects must not be pregnant and must be willing to use adequate contraception during the study period.

Exclusion Criteria:

  1. Current or history of psychotic symptoms.
  2. Active suicidal ideation (defined as a score of ≥3 on HDRS suicide item).
  3. Prior use of a TNF-alpha antagonist (i.e. etanercept, infliximab, adalimumab) and use of any other immunosuppressant agent (i.e. systemic corticosteroids or anti-proliferative agents such as methotrexate) within one year of study entry.
  4. Current use of aspirin, non-steroidal anti-inflammatory agents (NSAIDs) or COX-2 inhibitors during the study. Acetaminophen will be allowed.
  5. 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.
  6. Subjects will be excluded for a positive anti-double stranded DNA antibody test.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00463580

Sponsors and Collaborators
Emory University
National Institute of Mental Health (NIMH)
Principal Investigator: Andrew H. Miller, MD Emory University

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Andrew H Miller, Professor, Emory University Identifier: NCT00463580     History of Changes
Other Study ID Numbers: IRB00011734
1R21MH077172-01A2 ( U.S. NIH Grant/Contract )
First Posted: April 20, 2007    Key Record Dates
Results First Posted: May 12, 2014
Last Update Posted: March 29, 2018
Last Verified: February 2018

Keywords provided by Andrew H Miller, Emory University:
TNF-alpha antagonist
treatment resistant depression
major depressive disorder (MDD)
bipolar I disorder
bipolar II disorder

Additional relevant MeSH terms:
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents