Dynamics of Inflammation and Its Blockade on Motivational Circuitry in Depression

NCT03006393 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: IRB00087941R01MH108605
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Depression

Keywords

Neuroscience; Behavioral; Social

Outcome Measures

Primary Outcomes (1)

• Effort-based Decision-making (EBDM) Task Score

  Reward motivation was assessed by a laboratory effort-based decision-making (EBDM) task. On each trial, participants make a choice about expending more or less physical effort (rapid button pressing) in exchange for varying amounts of monetary rewards. Models of subjective value were fit to each participants' data using maximum likelihood estimation and were compared using Bayesian Information Criterion to identify the model that provides the best fit for participants' responses. Discounting functions were based on previous work and include linear, quadratic, hyperbolic, flexible power models. Models considering the potential effects of fatigue and examination of post-scan switching behavior were also evaluated. The best-fitting model from baseline data was applied to look at changes related to infliximab. Reported values reflect a model-derived summary statistic for effort discounting behavior, without a fixed range, where lower values associated with greater motivation.

  Baseline, Day 14

Secondary Outcomes (2)

• Plasma C-reactive Protein (CRP) Level

  Baseline, Day 14

• Plasma Interleukin-6 (IL-6) Level

  Baseline, Day 14

Study Arms (2)

Infliximab

EXPERIMENTAL

Participants randomized to the infliximab group will receive one infusion of infliximab at 5mg/kg body weight.

Drug: Infliximab

Placebo

PLACEBO COMPARATOR

Participants randomized to the placebo group will receive one placebo infusion.

Other: Placebo

Interventions

Infliximab DRUG

One infusion of Infliximab (Remicade) will be administered intravenously (IV) at 5 mg/kg body weight over a two hour period.

Also known as: Remicade

Infliximab

Placebo OTHER

One infusion of placebo treatment will be administered intravenously (IV) over a two hour period.

Also known as: Saline Solution

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects will be fully ambulatory and in good medical health. Note: By Diagnostic and Statistical Manual of Mental Disorders (DSM-4) definition of depression, subjects will report impairment in ability to carry out daily activities as a result of their major depression.
• Subjects will be able to read and understand English.
• Women must be postmenopausal (no menstrual period for a minimum of 1 year) or surgically sterilized and/or have a negative serum pregnancy test within thirty days of infusion (may be repeated closer to infusion date if deemed necessary by the PI or PI's designee) and negative urine pregnancy tests throughout the study (performed at each visit after the serum pregnancy test is completed).
• Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.
• The following are considered eligible according to the following tuberculosis (TB) screening criteria:
• Have no history of latent or active TB prior to screening.
• Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
• Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation to rule out infection. The candidate will be excluded from study participation if the specialist diagnoses active TB and or determines TB treatment is warranted.
• Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB.
• History of negative purified protein derivative (PPD) test; or documentation of a negative blood test (Quantiferon-TB-Gold). Any candidate testing positive for tuberculosis in the medical screening evaluation, will be excluded from study participation

You may not qualify if:

• Subjects will be excluded for any prior use of a TNF-alpha antagonist (i.e. etanercept, infliximab, adalimumab) and/or use of any other immunosuppressant agent (i.e. systemic corticosteroids or anti-proliferative agents such as methotrexate) within one year of study entry.
• Subjects chronically (i.e. more than one month) taking more than the equivalent of 2 mg of lorazepam a day of a benzodiazepine will be excluded.
• Subjects will be required not to use anti-inflammatory agents, non-steroidal anti-inflammatory agents (NSAIDs) (excluding 81mg of aspirin), glucocorticoid containing medicines or statins, or cyclooxygenase-2 (COX-2) inhibitors during the study as these agents may interfere with assessment of the relationship between inflammatory markers and treatment response.
• Note: Acetaminophen will be allowed.
• Potential subjects will be excluded for a history of any of the following conditions:
• Abnormal electrocardiogram
• Auto-immune condition as confirmed by laboratory testing (i.e. rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, lupus)
• History of significant infectious sequelae, including but not limited to, abscess or sepsis
• Infection within one month prior to screening that required antibiotic or antiviral therapy
• History of a more than mild cognitive disorder or ≤ 24 on the Mini-Mental State Exam (MMSE), unless otherwise approved by PI or his designee
• Unstable cardiovascular or endocrinologic disease (as determined by physical examination and/or laboratory testing)
• Any other current or past medical condition that might increase the risk of infliximab-related adverse events
• Potential subjects will be excluded for any of the following conditions:
• Active suicidal ideation defined as a score of ≥3 on Columbia Suicide Severity Rating Scale (C-SSR).
• Suicide attempt within six months of study entry

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Lee Y, Subramaniapillai M, Brietzke E, Mansur RB, Ho RC, Yim SJ, McIntyre RS. Anti-cytokine agents for anhedonia: targeting inflammation and the immune system to treat dimensional disturbances in depression. Ther Adv Psychopharmacol. 2018 Nov 19;8(12):337-348. doi: 10.1177/2045125318791944. eCollection 2018 Dec.

  PMID: 30524702 DERIVED

MeSH Terms

Conditions

Depression; Behavior

Interventions

Infliximab; Saline Solution

Condition Hierarchy (Ancestors)

Behavioral Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Michael Treadway
• Organization: Emory University

mtreadway@emory.edu

(404) 727-3166

Study Officials

• Michael Treadway, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: December 30, 2016
• Study Start: August 1, 2016
• Primary Completion: September 26, 2020
• Study Completion: September 26, 2020
• Last Updated: November 18, 2021
• Results First Posted: October 19, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)