Dynamics of Inflammation and Its Blockade on Motivational Circuitry in Depression
Condition: Depression
MeSH terms: Inflammation; Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      The main purpose of this study is to examine the effects of infliximab on measures related to
      depression symptoms. Infliximab is also known by its brand name Remicade. Infliximab, or
      Remicade, is given to by an intravenous (IV) needle and is currently used to treat rheumatoid
      arthritis and Crohn's disease. Infliximab is thought to help these conditions because it
      reduces inflammation in the body. Infliximab (Remicade) reduces inflammation by blocking a
      chemical in the body called tumor necrosis factor (TNF)-alpha. This chemical produces
      inflammation. Inflammatory chemicals in the body like TNF-alpha appear to be increased in
      some people with major depression. Researchers believe that a drug like infliximab, which
      blocks TNF-alpha, may be helpful in treating depression.

      This is a double-blind, placebo-controlled study in which participants will be randomized to
      receive one infusion of infliximab or placebo. The study will assess neuroimaging measures of
      corticostriatal circuitry before and after a placebo-controlled pharmacologic blockade of
      inflammation in 80 depressed patients.
    

Detailed description: 
      The main purpose of this study is to examine the effects of infliximab on measures related to
      depression symptoms. Infliximab is also known by its brand name Remicade. Infliximab, or
      Remicade, is given by an intravenous (IV) needle and is currently used to treat rheumatoid
      arthritis and Crohn's disease. Infliximab is thought to help these conditions because it
      reduces inflammation in the body. Infliximab (Remicade) reduces inflammation by blocking a
      chemical in the body called tumor necrosis factor (TNF)-alpha. This chemical produces
      inflammation. Inflammatory chemicals in the body like TNF-alpha appear to be increased in
      some people with major depression. Researchers believe that a drug like infliximab, which
      blocks TNF-alpha, may be helpful in treating depression.

      This is a double-blind, placebo-controlled study in which participants will be randomized to
      receive one infusion of infliximab or placebo. This study will assess neuroimaging measures
      of corticostriatal circuitry before and after a placebo-controlled pharmacologic blockade of
      inflammation in 80 depressed patients (n = 40 per group) recruited to ensure high levels of
      peripheral inflammation (CRP > 3mg/L).

      Primary aims are to evaluate whether 1) corticostriatal function during reward motivation and
      anticipation are associated with change in peripheral inflammation following pharmacologic
      blockade relative to placebo 2) the temporal dynamics of change in inflammation, gene-
      expression, reward motivation and reinforcement learning behavior and motivational symptoms
      assessed at baseline, and 24 hours, 3 days, 1 week and two weeks post infliximab infusion,
      and 3) test an integrative multi- level path model to determine whether change in
      corticostriatal circuitry following inflammation blockade mediates the relationship between
      change in inflammation and change in motivational anhedonia symptoms.

      These data will provide further validation of inflammatory cytokines as therapeutic targets
      for motivational symptoms in depression and will define symptom targets and biomarkers of
      response for future studies.
    

Intervention name(s): Infliximab; Placebo
Intervention type(s): Drug; Other
Intervention description(s): One infusion of Infliximab (Remicade) will be administered intravenously (IV) at 5 mg/kg body weight over a two hour period.; One infusion of placebo treatment will be administered intravenously (IV) over a two hour period.
Other intervention name(s): Remicade; Saline Solution
Intervention MeSH terms: Infliximab
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Neuroscience; Behavioral; Social