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DepressionPhase 4NCT03006393

Dynamics of Inflammation and Its Blockade on Motivational Circuitry in Depression

A Phase 4 study testing Infliximab in people with Depression, run by Emory University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 to 65 years
Conditions the study is for
Depression
What is being tested?
Infliximab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
42 participants
Where
1 siteUnited States
Study dates
Aug 2016to 26 Sep 2020
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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
  • Schizophrenia or Schizoaffective Disorder
  • Active Eating Disorder (excluding binge-eating disorder)
  • History of any (non-mood related) psychotic disorder or active psychotic symptoms of any type
  • Subjects will have had no infectious illnesses for one month prior to infusion. Should a subject develop an infection (i.e. flu, upper respiratory viral infection) between screening and infusion, the infusion will be delayed until 4 weeks after resolution of symptoms. As noted above, patients with a chronic infectious condition or with a past history of serious infectious complications will be excluded.
  • Subjects will be excluded for any evidence on laboratory testing (or by history) of hematologic, renal or hepatic abnormality. Subjects will be excluded for a positive anti-nuclear antibody (ANA) test.
  • Infliximab Related Exclusion Criteria:
  • Have had any previous treatment with monoclonal antibodies or antibody fragments.
  • History of receiving human/murine recombinant products or a known allergy to murine products. A known allergy to murine product is definitely an exclusion criterion.
  • Documentation of seropositive for human immunodeficiency virus (HIV). Any candidate testing positive for HIV, in the medical screening evaluation, will be excluded from study participation.
  • Documentation of a positive test for hepatitis B surface antigen or hepatitis C. Any candidate testing positive for hepatitis B or hepatitis C, in the medical screening evaluation, will be excluded from study participation.
  • Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
  • Use of any investigational drug within 30 days prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
  • Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening).
  • Have a concomitant diagnosis or history of congestive heart failure.
  • Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results. (As determined by Structured Clinical Interview for DSM-5 (SCID-5))
  • Have a known history of serious infections (e.g., hepatitis, pneumonia, or pyelonephritis) in the previous 3 months.
  • Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.
  • Have a history of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (e.g., nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic area), or splenomegaly.
  • Currently have any known malignancy other than the condition being treated or have a history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Emory University

    Atlanta, Georgia, 30322

Other trials in United States

About this study

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.

Read the 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.

Conditions
Depression
Being tested
Infliximab, Placebo
Keywords
Neuroscience, Behavioral, Social
Medical subject headings
Depression, Behavior

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InfliximabDrug

    Also called Remicade

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

  • PlaceboOther

    Also called Saline Solution

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

Study groups in NCT03006393
Study groupRoleWhat they receive
InfliximabExperimentalParticipants randomized to the infliximab group will receive one infusion of infliximab at 5mg/kg body weight.
Receives: Drug: Infliximab
PlaceboPlacebo comparatorParticipants randomized to the placebo group will receive one placebo infusion.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline, Day 14

Secondary outcomes (2)
  1. Plasma C-reactive Protein (CRP) Level

    C-reactive protein (CRP) is a blood test marker for inflammation in the body. CRP is produced in the liver and its level is measured by testing the blood. CRP level was measured at baseline and Day 14. Lower result correlates with better outcome.

    Measured: Baseline, Day 14

  2. Plasma Interleukin-6 (IL-6) Level

    Plasma IL-6 level will be collected via blood draw. IL-6 level was collected at baseline and Day 14. Lower result correlates with better outcome.

    Measured: Baseline, Day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Dec 2016 (estimated)
  2. Study startAug 2016
  3. Primary completion26 Sep 2020
  4. Study completion26 Sep 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03006393
Sponsor's protocol ID
IRB00087941
Other IDs
R01MH108605
Status last verified
Oct 2021
First submitted
28 Dec 2016
Last updated
18 Nov 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 30524702

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Infliximab in people with Depression, run by Emory University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effort-based Decision-making (EBDM) Task Score (time frame: Baseline, Day 14). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03006393, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2021.

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