Major Depressive DisorderPhase 2NCT07908563
Dupilumab in Major Depressive Disorder
A Phase 2 study testing Dupilumab Injection in people with Major Depressive Disorder, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
This study aims primarily to test target engagement of dupilumab by assessing changes in peripheral immune markers following interleukin-4 receptor alpha (IL-4Rα) blockade in adults with major depressive disorder (MDD). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Dupilumab Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Aug 2026to Dec 2028
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written informed consent (and assent when applicable) obtained from subject;
- Ability for the subject to comply with the requirements of the study as determined by the PI;
- Men and women, age 18-65 years;
- Participants must meet DSM-5 criteria for Major Depressive Disorder [MDD]) in a current major depressive episode (MDE) as determined by a study psychiatrist and confirmed using the Structured Clinical Interview for DSM-5 Research Version (SCID-5-RV);
- If patient is taking antidepressant medication, they must be on a stable dose for at least 4 weeks prior to baseline (6 weeks for fluoxetine);
- Quick Inventory of Depressive Symptoms - Clinician Administered (QIDS-C) score ≥ 14;
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- If female of childbearing potential, must agree to use of a medically accepted form of contraception (including barrier contraception such as condoms, oral contraceptive pills, or intrauterine devices) starting at least one cycle prior to study drug initiation, or else agree to abstinence until 6 months after the last dose of study drug.
- Male patients, if heterosexually active with a partner who is female of childbearing potential, pregnant, or breastfeeding, must agree to barrier contraception for the treatment period and for at least 6 months after the last dose of study drug. Female partners of male participants must use at least one form of medically accepted contraception starting at least one cycle prior to male patient study drug initiation until 6 months after the last dose of study drug.
- Written informed consent obtained from subject;
- Ability for the subject to comply with the requirements of the study as determined by the PI;
- Ages 18-65, any gender;
- No current or past DSM-5 psychiatric disorder as determined by SCID-5-RV or MINI;
- Meet all MRI safety criteria.
Who cannot join
- A primary psychiatric diagnosis other than MDD as defined by DSM-5; [comorbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder and panic disorder) and posttraumatic stress disorder (PTSD) are allowed];
- Has a history of schizophrenia or other psychotic disorder, major depressive disorder with psychotic features, or bipolar I or II disorder;
- Diagnosis of a major neurocognitive disorder;
- Meets criteria for a moderate or severe substance use disorder within the past 6 months, with the exception of nicotine use disorder;
- Any contraindication to MRI including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, or inability to lie still for 1 hour or more;
- Positive urine toxicology screen for illicit drugs (other than cannabis) at the time of screening;
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- Serious and imminent risk of self-harm or violence as determined by the PI;
- History of suicide attempt in the past 2 years or screening CSSRS Ideation Score >2 in the past month;
- Clinically significant abnormalities of laboratory tests or physical examination;
- Unstable medical illnesses including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic/inflammatory, hematologic disease, or other medical conditions or abnormality (including relevant laboratory abnormalities at screening) that, in the opinion of the investigator, may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study patient as a result of his/her participation in the study, may make patient's participation unreliable, may interfere with study assessments, or may compromise the safety of the patient or the quality of the data;
- Concomitant treatments with other biologics or other immune-suppressant agents; PRN use of NSAIDs is permissible;
- Female participants who are pregnant, breastfeeding, or may become pregnant, or unwilling to practice birth control during participation in the study or the 6 months following. Male participants or the female partners who are unwilling to adhere to the birth control requirements specified in Section 5.1 (points 8 and 9);
- Presence of a known hypersensitivity to dupilumab or any excipients in dupilumab, or planned upcoming receipt of a live vaccination, or receipt of a live attenuated vaccination within 30 days prior to the receipt of the first dupilumab injection;
- Presence of an active tuberculosis infection, untreated latent TB, or a positive result on TB test (Quantiferon Gold) at screening, as well as known history of human immunodeficiency virus (HIV) infection, Hepatitis B, and/or Hepatitis C.
- History of malignancy within 5 years of baseline assessment (excluding non-melanoma skin cancers).
- Any unstable medical illnesses including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
- Concomitant treatments with other biologics or other immune-suppressant agents (PRN use of NSAIDs is permissible);
- Female participants who are pregnant at the time of baseline assessments (e.g., MRI);
- Positive urine toxicology screen for illicit drugs at the time of screening.
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
The Dennis S. Charney, MD, Depression and Anxiety Discovery Center
New York, New York, 10029
Mackenzie B Hargrove, MPH, 332-243-7052, mackenzie.brown@mssm.edu
Alexia Lizzano, BS, 332-243-7059, alexia.lizzano@mssm.edu
About this study
Official title: Target Validation of Interleukin-4 Receptor Alpha for Major Depressive Disorder
This study aims primarily to test target engagement of dupilumab by assessing changes in peripheral immune markers following interleukin-4 receptor alpha (IL-4Rα) blockade in adults with major depressive disorder (MDD). Secondary aims include evaluating safety, tolerability, feasibility, and open-label effects on depressive symptoms, blood-based immune markers, blood-brain barrier (BBB) function, and functional brain reward circuitry.
Read the detailed description
The proposed study aims to test interleukin-4 receptor alpha (IL-4α) as a novel immune target for major depressive disorder (MDD). The study will also evaluate whether the effects of dupilumab on blood immune markers are associated with changes in brain reward circuitry and depressive symptoms, and thereby providing mechanistic insight into its potential antidepressant effects. Dysregulation of blood immune markers has been previously demonstrated in patients with MDD. Dupilumab binds to IL-4-alpha receptors (IL-4Rα), blocking IL-4 and IL-13 and, consequently, downstream Th2 and other immune signaling pathways. Dupilumab has been associated with improvement of depressive symptoms when used for treatment of inflammatory allergic disorders such as atopic dermatitis, but has never been tested in primary depressive disorders. This study is an open-label trial where N=14 patients with MDD will be treated with dupilumab for 8 weeks. A healthy control (HC) group (N=20) will undergo clinical and immune assessments at baseline and after 8 weeks, but will not receive study drug and will serve as a reference group to account for longitudinal variability in biomarker and behavioral measures overtime. Blood-based immune markers will be assessed, and brain MRI scans will be administered before and after the treatment period. Behavioral tasks assessing reward processing and motivation will also be administered to examine relationships between immune modulation and behavioral function. End of treatment (EOT) is defined as Week 9, which occurs two weeks after the final dupilumab dose administered at Week 7.
- Conditions
- Major Depressive Disorder
- Being tested
- Dupilumab Injection
- Keywords
- interleukin-4, dupixent, monoclonal antibody, inflammation, dupilumab, IL-4
- Medical subject headings
- Depressive Disorder, Major, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dupilumab InjectionDrug
At baseline (visit 0), participants in the major depressive disorder (MDD) arm will receive a subcutaneous injection of 600 mg of dupilumab. At visits 1 through 7, MDD participants will receive a 300 mg injection of dupilumab.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Control | No intervention | A healthy control group will undergo clinical and immune assessments at baseline and after 8 weeks, but will not receive the study drug and will serve as a reference group to the major depressive disorder arm of the study. |
| Major Depressive Disorder | Experimental | Participants diagnosed with major depressive disorder (MDD) will receive a total of 8 weekly subcutaneous injections of dupilumab over the course of 8 weeks. Receives: Drug: Dupilumab Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Interleukin-4 receptor alpha (IL-4α)
To test interleukin-4 receptor alpha (IL-4α) as a novel therapeutic immune target for MDD by quantifying within-subject changes in peripheral immune markers using the Olink platform.
Measured: Baseline and end of treatment at week 9
Secondary outcomes (5)
Response Rate
To examine response rate with dupilumab treatment defined as ≥ 50% MADRS total score improvement.
The Montgomery-Asberg Depression Rating Scale (MADRS) has 10 items that are based on mood symptoms over the past 7 days. Each item is scored 0 (normal) to 6 (severe depression) with overall total score ranges from 0 - 60. A higher score indicates more severe depression.
Response is defined as an improvement in a patient's health status, a reduction in disease activity, or a measurable therapeutic effect following an intervention.
Measured: End of treatment (week 9)
Remission Rate
To examine remission rate with dupilumab treatment defined as a MADRS total score of ≤ 10.
The Montgomery-Asberg Depression Rating Scale (MADRS) has 10 items that are based on mood symptoms over the past 7 days. Each item is scored 0 (normal) to 6 (severe depression) with overall total score ranges from 0 - 60. A higher score indicates more severe depression.
Remission is defined as a reduction or complete disappearance of the signs and symptoms of a disease.
Measured: End of treatment (week 9)
The Montgomery-Asberg Depression Rating Scale (MADRS)
To examine changes in depression severity as assessed by the Montgomery-Asberg Depression Rating Scale (MADRS). The Montgomery-Asberg Depression Rating Scale (MADRS) has 10 items that are based on mood symptoms over the past 7 days. Each item is scored 0 (normal) to 6 (severe depression) with overall total score ranges from 0 - 60. A higher score indicates more severe depression.
Measured: Weekly from baseline through end of treatment at week 9
Change in ventral stratal activation
To examine changes in ventral stratal activation (brain response) during reward processing (fMRI).
Measured: Baseline and end of treatment at week 9
Internal-External Motivation Task (IMT)
To examine the relationship between immune modulation and behavioral measures of reward processing and motivation.
Reward processing will be measured with the Internal-External Motivation Task (IMT). The IMT is a 15-minute effort-discounting decision-making task.
Measured: Baseline and end of treatment at week 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2026
- Study start27 Aug 2026
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- Wellcome Trust
- Responsible party
- Principal investigator, James Murrough, Icahn School of Medicine at Mount Sinai
- Investigators
- James W Murrough, MD, PhD, Principal investigator, Icahn School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07908563
- Sponsor's protocol ID
- STUDY-23-00782
- Other IDs
- 329930/Z/25/Z
- Status last verified
- Oct 2026
- First submitted
- 26 Oct 2026
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Target Validation of Interleukin-4 Receptor Alpha for Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT07908563
- Acronym / sponsor ID
- STUDY-23-00782
- Conditions
- Major Depressive Disorder
- Keywords
- interleukin-4, dupixent, monoclonal antibody, inflammation, dupilumab, IL-4
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- Wellcome Trust
- Study start
- 27 Aug 2026 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 2 Nov 2026 (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 aims primarily to test target engagement of dupilumab by assessing changes in peripheral immune markers following interleukin-4 receptor alpha (IL-4Rα) blockade in adults with major depressive disorder (MDD). Secondary aims include evaluating safety, tolerability, feasibility, and open-label effects on depressive symptoms, blood-based immune markers, blood-brain barrier (BBB) function, and functional brain reward circuitry.
Detailed description
The proposed study aims to test interleukin-4 receptor alpha (IL-4α) as a novel immune target for major depressive disorder (MDD). The study will also evaluate whether the effects of dupilumab on blood immune markers are associated with changes in brain reward circuitry and depressive symptoms, and thereby providing mechanistic insight into its potential antidepressant effects. Dysregulation of blood immune markers has been previously demonstrated in patients with MDD. Dupilumab binds to IL-4-alpha receptors (IL-4Rα), blocking IL-4 and IL-13 and, consequently, downstream Th2 and other immune signaling pathways. Dupilumab has been associated with improvement of depressive symptoms when used for treatment of inflammatory allergic disorders such as atopic dermatitis, but has never been tested in primary depressive disorders. This study is an open-label trial where N=14 patients with MDD will be treated with dupilumab for 8 weeks. A healthy control (HC) group (N=20) will undergo clinical and immune assessments at baseline and after 8 weeks, but will not receive study drug and will serve as a reference group to account for longitudinal variability in biomarker and behavioral measures overtime. Blood-based immune markers will be assessed, and brain MRI scans will be administered before and after the treatment period. Behavioral tasks assessing reward processing and motivation will also be administered to examine relationships between immune modulation and behavioral function. End of treatment (EOT) is defined as Week 9, which occurs two weeks after the final dupilumab dose administered at Week 7.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Control | No intervention | –A healthy control group will undergo clinical and immune assessments at baseline and after 8 weeks, but will not receive the study drug and will serve as a reference group to the major depressive disorder arm of the study. |
| Major Depressive Disorder | Experimental | Drug: Dupilumab InjectionParticipants diagnosed with major depressive disorder (MDD) will receive a total of 8 weekly subcutaneous injections of dupilumab over the course of 8 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Written informed consent (and assent when applicable) obtained from subject;
- Ability for the subject to comply with the requirements of the study as determined by the PI;
- Men and women, age 18-65 years;
- Participants must meet DSM-5 criteria for Major Depressive Disorder [MDD]) in a current major depressive episode (MDE) as determined by a study psychiatrist and confirmed using the Structured Clinical Interview for DSM-5 Research Version (SCID-5-RV);
- If patient is taking antidepressant medication, they must be on a stable dose for at least 4 weeks prior to baseline (6 weeks for fluoxetine);
Key exclusion criteria (19 listed)
- A primary psychiatric diagnosis other than MDD as defined by DSM-5; [comorbid anxiety disorders (including agoraphobia, generalized anxiety disorder, social anxiety disorder and panic disorder) and posttraumatic stress disorder (PTSD) are allowed];
- Has a history of schizophrenia or other psychotic disorder, major depressive disorder with psychotic features, or bipolar I or II disorder;
- Diagnosis of a major neurocognitive disorder;
- Meets criteria for a moderate or severe substance use disorder within the past 6 months, with the exception of nicotine use disorder;
- Any contraindication to MRI including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, or inability to lie still for 1 hour or more;
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 |
|---|---|---|
| Dupilumab InjectionAt baseline (visit 0), participants in the major depressive disorder (MDD) arm will receive a subcutaneous injection of 600 mg of dupilumab. At visits 1 through 7, MDD participants will receive a 300 mg injection of dupilumab. | Drug | Major Depressive Disorder |
Primary outcome
Interleukin-4 receptor alpha (IL-4α)
Time frame: Baseline and end of treatment at week 9
To test interleukin-4 receptor alpha (IL-4α) as a novel therapeutic immune target for MDD by quantifying within-subject changes in peripheral immune markers using the Olink platform.
5 secondary outcomes
Response Rate
Time frame: End of treatment (week 9)
Remission Rate
Time frame: End of treatment (week 9)
The Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Weekly from baseline through end of treatment at week 9
Change in ventral stratal activation
Time frame: Baseline and end of treatment at week 9
Internal-External Motivation Task (IMT)
Time frame: Baseline and end of treatment at week 9
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 2 Nov 2026.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
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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.
James W Murrough, MD, PhD principal investigator
Icahn School of Medicine
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 Dupilumab Injection in people with Major Depressive Disorder, run by Icahn School of Medicine at Mount Sinai 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 13 inclusion and 19 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 2 Nov 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. 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 Mackenzie B Hargrove, MPH (332-243-7052, mackenzie.brown@mssm.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Interleukin-4 receptor alpha (IL-4α) (time frame: Baseline and end of treatment at week 9). 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 2 Nov 2026.