A Study of Infliximab for Treatment Resistant Major Depression
Status:
Completed
Trial end date:
2011-06-01
Target enrollment:
Participant gender:
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. The researchers 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 drawn 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.