Depressive Disorder, MajorPhase 2NCT06136546
Cognitive Dysfunction and Inflammation in Depression: Experimental Inhibition Via Infliximab
A Phase 2 study testing Infliximab in people with Depressive Disorder, Major and Inflammation, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study is a mechanistic randomized controlled trial that investigates whether inhibition of tumor necrosis factor signaling via intravenous infusion of infliximab improves psychomotor speed and executive functioning in depressed individuals who exhibit an inflammatory phenotype. Read more about this study
- Who is it for?
- Ages 25 to 50 years
- Conditions the study is for
- Depressive Disorder, Major, Inflammation
- 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
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jan 2025to 31 Jan 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 25 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Aged 25-50 years.
- Able to read and understand English and willing to provide informed consent/comply with the study protocol.
- Willingness to complete intravenous infusion and have blood drawn.
- Exhibit circulating blood level of C reactive protein ≥ 2mg/L at both screening and baseline visits.
- Diagnosed with Major Depressive Disorder.
- Moderate depressive symptom severity, as indicated by score ≥14 on the Hamilton Depression Rating Scale.
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- Antidepressant treatment free for at least 4 weeks prior to study entry or be on a fixed treatment regimen for at least 4 weeks; willingness to continue treatment status (i.e., change/begin new treatment) until study termination.
- Willingness not to begin/change therapies until study termination (maximum of three weeks following screening).
- Be of non-childbearing potential per the following specific criteria:
- Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal ligation), or is post-menopausal with her last menses at least one year prior to screening); or b. Childbearing potential and meets the following criteria: i. A negative serum pregnancy test within thirty days of infusion (may be repeated closer to infusion date at the discretion of the PI or study staff) and abstinent after the negative serum pregnancy test and prior to infusion; or ii. Using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or is sexually abstinent; iii. Continuously use one of the following methods of birth control over the last six months: implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence.
Who cannot join
- Medical conditions that could confound interpretation or increase participant risk, as indicated via medical history or laboratory testing; exclusionary medical conditions will include:
- acute injury/infection within one week of study initiation or infection within one month of study initiation that required antibiotic/antiviral treatment; or ii. chronic infection (e.g., hepatitis B or C or HIV) or history of Covid 19 infection within the past 6 months or with persisting symptoms; or iii. latent infection (e.g., tuberculosis, fungal infections), or history of recurrent infections; or iv. uncontrolled cardiovascular, endocrine, hematologic, hepatic, renal or neurologic disease (as determined by medical history, physical exam and laboratory testing); or v. cancer history; or vi. autoimmune conditions; or vii. neurologic conditions (controlled) that substantially impacted cognitive function (e.g., stroke).
- Of note, stable medical conditions such as diabetes and cardiovascular disease, will be allowed in the study as they can contribute to endogenous inflammation.
- Active antipsychotic and anticonvulsant medication use (that interact with infliximab).
- Prior use of a TNF antagonist or use of systemic corticosteroids or anti-proliferative agents within 6 months of study entry.
- History of liver abnormalities.
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- Major cognitive impairment as determined by study investigators.
- Active restrictive eating disorder or obsessive compulsive disorder deemed by study investigators to be primary cause of depressive disorder.
- History of a psychotic disorder or Bipolar disorder type I/II.
- Current substance use disorder (i.e., present in last six months), of greater than mild severity.
- Suicidal ideation based on a score ≥3 on the Columbia-Suicide Severity Rating Scale.
- Electroconvulsive therapy (ECT)/deep brain stimulation (DBS) within the last year, or report of persistent negative cognitive effects of ECT/DBS.
- Presence of a transplanted solid organ.
- Medication use affecting immune or cognitive function:
- Chronic use (>1 month) of a benzodiazepine more than the equivalent of 2 mg of lorazepam; or ii. Use of anti-inflammatory agents during the study: non-steroidal anti-inflammatory agents (NSAIDs) (excluding 81mg of aspirin), glucocorticoid containing medicines or statins, or cyclooxygenase-2 (COX-2) inhibitors; or iii. Anti-histamine use within 24-48 hours of cognitive testing; or iv. Use of topical steroids with a large area of application (more than the size of silver dollar coin); or v. Inhaled steroids taken more than 2-3 times per week.
- Considered by the study investigators to be inappropriate for the study due to safety concerns or to be unlikely to complete the protocol.
- History of allergic response to murine products.
- Received a live vaccine within the last 6 weeks.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Naoise Mac Giollabhui, PhD, 6177241000, nmacgiollabhui@mgh.harvard.edu
Naoise Mac Giollabhui, PhD
About this study
Official title: The Role of Inflammation in Cognitive Dysfunction in Acute Depression as Determined by Experimental Inhibition of Tumor Necrosis Factor-alpha Signaling in a Randomized Controlled Trial.
This study is a mechanistic randomized controlled trial that investigates whether inhibition of tumor necrosis factor signaling via intravenous infusion of infliximab improves psychomotor speed and executive functioning in depressed individuals who exhibit an inflammatory phenotype.
Read the detailed description
In this mechanistic RCT, depressed adults who exhibit a pro-inflammatory phenotype (C reactive protein ≥2mg/L) will be randomized on a 1:1 allocation to receive a TNF inhibitor (infliximab) or placebo. Over a two-week follow-up, participants will remotely complete brief, daily assessments of depressive symptoms and psychomotor speed/executive functioning using a mobile-based platform (TestMyBrain) in addition to in-person clinician-rated assessment of depressive symptom severity (Hamilton Depression Rating Scale), anhedonia (Dimensional Anhedonia Rating Scale), and more comprehensive computerized batteries assessing cognitive function (TestMyBrain). Blood will be drawn at baseline and week 1 to assess immune biomarkers (C reactive protein, tumor necrosis factor- alpha and its soluble receptors). Specifically, the study will determine whether randomization to infliximab is associated with improvement in psychomotor speed and executive function.
- Conditions
- Depressive Disorder, Major, Inflammation
- Being tested
- Infliximab, Placebo
- Keywords
- Depression, Major Depressive Disorder, Infliximab, Cognitive Dysfunction
- Medical subject headings
- Depressive Disorder, Major, Inflammation, Depression, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Intravenous infusion of infliximab
PlaceboOther
Intravenous infusion of saline solution (matching in color and consistency in infliximab)
| Study group | Role | What they receive |
|---|---|---|
| Infliximab | Experimental | Participants in this arm will receive 5 mg/kg of infliximab via an in-dwelling catheter. Receives: Drug: Infliximab |
| Placebo | Placebo comparator | Participants in this arm will receive saline as placebo via an in-dwelling catheter. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Executive Function (TestMyBrain: Choice Reaction Time - Median Response Time on Correct Trials)
Better within-person executive function performance (i.e. accuracy-adjusted response speed)
Measured: Repeated measures over two weeks
Secondary outcomes (8)
Hamilton Depression Rating Scale (17-item; range 0-54)
Reduced depressive symptoms severity
Measured: Week 2
Dimensional Anhedonia Rating Scale (17-item; range 0-68)
Reduced anhedonia
Measured: Week 2
Concentrations of circulating C reactive protein
Reduced circulating C reactive protein
Measured: Week 1
Processing Speed (TestMyBrain: Matching Shapes and Numbers - Number of Correct Responses)
Total number of correct matches in the timed task
Measured: Repeated measures over two weeks
Psychomotor Speed (TestMyBrain: Fast Reactions - Median Reaction Time)
Median latency across valid responses, in milliseconds
Measured: Repeated measures over two weeks
Self-reported Depressive Symptom Severity (PROMIS Short Form v1.0 - Depression 4a)
Total score
Measured: Repeated measures over two weeks
Self-reported Cognitive Difficulties (PDQ-20: Perceived Deficits Questionnaire)
Total score on 20-item self-report measure developed to assess cognitive symptoms in major depressive disorder.
Measured: Week 2
Self-reported Cognitive Difficulties (PROMIS v2.0 Cognitive Function 8a)
Total score on 8-item self-report measure assessing perceived cognitive abilities in everyday life, including concentration, memory, and mental clarity.
Measured: Week 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2023
- Study start23 Jan 2025
- Primary completion31 Aug 2028 (estimated)
- Study completion31 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A permuted block design (n=4) on a 1:1 allocation will be used to assign participants to each intervention group.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Naoise Mac Giollabhui, PhD, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06136546
- Sponsor's protocol ID
- 2023p002988
- Status last verified
- Oct 2026
- First submitted
- 13 Nov 2023
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Inflammation in Cognitive Dysfunction in Acute Depression as Determined by Experimental Inhibition of Tumor Necrosis Factor-alpha Signaling in a Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT06136546
- Acronym / sponsor ID
- 2023p002988
- Conditions
- Depressive Disorder, Major, Inflammation
- Keywords
- Depression, Major Depressive Disorder, Infliximab, Cognitive Dysfunction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 23 Jan 2025 (actual)
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- 31 Jan 2029 (estimated)
- First posted
- 18 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a mechanistic randomized controlled trial that investigates whether inhibition of tumor necrosis factor signaling via intravenous infusion of infliximab improves psychomotor speed and executive functioning in depressed individuals who exhibit an inflammatory phenotype.
Detailed description
In this mechanistic RCT, depressed adults who exhibit a pro-inflammatory phenotype (C reactive protein ≥2mg/L) will be randomized on a 1:1 allocation to receive a TNF inhibitor (infliximab) or placebo. Over a two-week follow-up, participants will remotely complete brief, daily assessments of depressive symptoms and psychomotor speed/executive functioning using a mobile-based platform (TestMyBrain) in addition to in-person clinician-rated assessment of depressive symptom severity (Hamilton Depression Rating Scale), anhedonia (Dimensional Anhedonia Rating Scale), and more comprehensive computerized batteries assessing cognitive function (TestMyBrain). Blood will be drawn at baseline and week 1 to assess immune biomarkers (C reactive protein, tumor necrosis factor- alpha and its soluble receptors). Specifically, the study will determine whether randomization to infliximab is associated with improvement in psychomotor speed and executive function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A permuted block design (n=4) on a 1:1 allocation will be used to assign participants to each intervention group.
| Arm | Type | Receives |
|---|---|---|
| Infliximab | Experimental | Drug: InfliximabParticipants in this arm will receive 5 mg/kg of infliximab via an in-dwelling catheter. |
| Placebo | Placebo comparator | Other: PlaceboParticipants in this arm will receive saline as placebo via an in-dwelling catheter. |
Who may qualify
- Ages
- 25 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Aged 25-50 years.
- Able to read and understand English and willing to provide informed consent/comply with the study protocol.
- Willingness to complete intravenous infusion and have blood drawn.
- Exhibit circulating blood level of C reactive protein ≥ 2mg/L at both screening and baseline visits.
- Diagnosed with Major Depressive Disorder.
Key exclusion criteria (18 listed)
- Medical conditions that could confound interpretation or increase participant risk, as indicated via medical history or laboratory testing; exclusionary medical conditions will include:
- Of note, stable medical conditions such as diabetes and cardiovascular disease, will be allowed in the study as they can contribute to endogenous inflammation.
- Active antipsychotic and anticonvulsant medication use (that interact with infliximab).
- Prior use of a TNF antagonist or use of systemic corticosteroids or anti-proliferative agents within 6 months of study entry.
- History of liver abnormalities.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InfliximabIntravenous infusion of infliximab | Drug | Infliximab |
| PlaceboIntravenous infusion of saline solution (matching in color and consistency in infliximab) | Other | Placebo |
Primary outcome
Executive Function (TestMyBrain: Choice Reaction Time - Median Response Time on Correct Trials)
Time frame: Repeated measures over two weeks
Better within-person executive function performance (i.e. accuracy-adjusted response speed)
8 secondary outcomes
Hamilton Depression Rating Scale (17-item; range 0-54)
Time frame: Week 2
Dimensional Anhedonia Rating Scale (17-item; range 0-68)
Time frame: Week 2
Concentrations of circulating C reactive protein
Time frame: Week 1
Processing Speed (TestMyBrain: Matching Shapes and Numbers - Number of Correct Responses)
Time frame: Repeated measures over two weeks
Psychomotor Speed (TestMyBrain: Fast Reactions - Median Reaction Time)
Time frame: Repeated measures over two weeks
Self-reported Depressive Symptom Severity (PROMIS Short Form v1.0 - Depression 4a)
Time frame: Repeated measures over two weeks
Self-reported Cognitive Difficulties (PDQ-20: Perceived Deficits Questionnaire)
Time frame: Week 2
Self-reported Cognitive Difficulties (PROMIS v2.0 Cognitive Function 8a)
Time frame: Week 2
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Infliximab in people with Depressive Disorder, Major and Inflammation, run by Massachusetts General Hospital 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 18 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: looking for participants now, as of the sponsor's last update on 27 Oct 2026. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Naoise Mac Giollabhui, PhD (6177241000, nmacgiollabhui@mgh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Executive Function (TestMyBrain: Choice Reaction Time - Median Response Time on Correct Trials) (time frame: Repeated measures over two weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Oct 2026.