Major Depressive DisorderPhase 2NCT07003997
JAK Signaling in Depression
A Phase 2 study testing Baricitinib in people with Major Depressive Disorder, run by Emory University at 1 site in United States.
Trial summary
This study will test the hypothesis that Janus kinase (JAK) signaling is involved in major depression (MD) with high inflammation by determining whether its inhibition with baricitinib can improve functional connectivity in reward and motor circuits in association with improved motivation and motor function in MD… Read more about this study
- Who is it for?
- Ages 25 to 55 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Baricitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Sep 2025to Feb 2030
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- willing and able to give written informed consent;
- men or women, 25-55 years of age;
- a primary diagnosis of DSM-V major depression, current, or Bipolar, depressed type as diagnosed by the SCID-V;
- score of >14 on the PHQ-9 from screening and HAM-D score ≥18 for study entry;
- off all antidepressant or other psychotropic therapy (e.g. mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks prior to baseline visit (8 weeks for fluoxetine),
- CRP ≥3 mg/L,
- PHQ-9 anhedonia score ≥2.
Who cannot join
- history or evidence (clinical and laboratory) of an autoimmune disorder
- history or evidence (clinical or laboratory) of hepatitis B or C infection or human immunodeficiency virus infection;
- history of any type of cancer requiring treatment with more than minor surgery;
- unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination, EKG and laboratory testing);
- significant hematological abnormalities at screening (ANC < 1500, Hgb<10, platelet< 100,000)
- history of progressive multifocal leukoencephalopathy,
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- history of deep venous thrombosis,
- history of cardiovascular disease (coronary artery disease, congestive heart failure, stroke - controlled hypertension is OK),
- major surgery within 8 weeks prior to screening or will require major surgery during the study,
- current or recent (<4 weeks prior to randomization) viral (including COVID-19), bacterial, fungal, or parasitic infection or any other active or recent infection,
- symptomatic herpes zoster infection at or within 12 weeks of randomization,
- history of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement),
- cirrhosis of the liver from any cause,
- any of the following specific abnormalities on screening laboratory tests: ALT or AST >2 x upper limits of normal (ULN), alkaline phosphatase (ALP) ≥2 x ULN, total bilirubin ≥1.5 x ULN (with the exception of patients on atazanavir, who must have total bilirubin <2 x ULN),
- chronic kidney disease with eGFR <60 mL/min/1.73 m2,
- history of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; substance abuse/dependence within 6 months of study entry (as determined by standardized clinician interview);
- active suicidal plan as determined by a score >3 on item #3 on the HAM-D; g. an active eating disorder (except for patients with binge eating disorder in whom binging is clearly associated with worsening of mood symptoms);
- history of a cognitive disorder or traumatic head injury involving loss of consciousness;
- pregnancy or lactation,
- use of gender affirming hormone therapy;
- chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), immunosuppressive (e.g., biologics), glucocorticoid containing medications or minocycline within 6 months, or non-prescription supplements with known or suspected anti-inflammatory properties (e.g. fish oil supplements) within 2 weeks of baseline, or at any time during the study;
- any contraindication for MRI scanning;
- failure of more than 3 antidepressant trials (at least 6 weeks at recommended dose) in the current episode or 5 antidepressant trials lifetime; and
- BMI >45 (to exclude severe obesity) or at the PI's discretion based on the patient's ability to fit comfortably in the MRI scanner.
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
Emory University
Atlanta, Georgia, 30322
Jennifer Felger, PhD
About this study
Official title: Janus Kinase (JAK) Signaling in Depression
This study will test the hypothesis that Janus kinase (JAK) signaling is involved in major depression (MD) with high inflammation by determining whether its inhibition with baricitinib can improve functional connectivity in reward and motor circuits in association with improved motivation and motor function in MD patients enriched for high C-reactive protein (CRP) and anhedonia.
Read the detailed description
Many people with depression also have high inflammation, which may be a cause of some of their depression symptoms. This study is being done to learn how inflammation affects the brain to cause symptoms of depression like anhedonia, low motivation and motor slowing. This will be tested using a medication called baricitinib that blocks one aspect of inflammation involving Janus kinase (JAK) signaling. The population to be included in this study are patients with depression and symptoms of anhedonia who have high inflammation as determined by a blood test. Patients must also be free of uncontrolled medical illnesses. Patients enrolled in the study will be randomly treated with either baricitinib or a placebo (matching sugar pill) for 8 weeks and assessed for markers of inflammation in the blood and symptoms of depression using self-reported and clinician-guided assessments. In addition, brain scans and computerized testing will be done to measure brain function and levels of motivation and motor speed. Participation in the study will include at least 8 visits over 2-3 months, including screening. Subjects will be recruited from local clinics and from the Atlanta community using social media ads. Approximately 100 subjects will be enrolled for this study to obtain 60 subjects who will be randomized to baricitinib or placebo. Blood and information from the brain scans, computerized testing and assessments of depression will be saved for future use. Consent to participate in the study will be obtained either remotely or in person by a trained staff member.
- Conditions
- Major Depressive Disorder
- Being tested
- Baricitinib, Placebo
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BaricitinibDrug
Also called Olumiant
This small molecule, orally bioavailable agent is an immunosuppressant (a medicine that reduces the activity of the immune system). It works by blocking the action of enzymes known as Janus kinases (JAK). These enzymes play an important role in the processes of inflammation. Patients will receive a dose of 2 mg oral daily. The dose will be increased to 4 mg/day (2 tablets/d of baricitinib) as tolerated for subjects that do not exhibit a clinical response at 4 Weeks (50% reduction in HAM-D scores) until end of treatment.
PlaceboDrug
Also called Sugar pill
A placebo is a sugar pill that has no therapeutic effect and will be administered orally. Participants will receive 1 placebo tablet matching the baricitinib tablet.
| Study group | Role | What they receive |
|---|---|---|
| Baricitinib Arm | Experimental | Baricitinib at dose of 2 mg (1 tablet) will be dispensed to be taken orally, daily for 8 weeks.
For subjects that do not exhibit a clinical response at 4 Weeks (50% reduction in HAM-D scores), the dose will be increased to 4 mg/day (2 tablets/day) as tolerated until end of treatment. Receives: Drug: Baricitinib |
| Placebo Arm | Placebo comparator | Placebo will be dispensed to be taken orally, daily for 8 weeks. For subjects that do not exhibit a clinical response at 4 Weeks (50% reduction in HAM-D scores), the dose will be increased to 2 tablets per day. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in corticostriatal FC in reward and motor circuits after 2 and 8 weeks of study medication
FC in the corticostriatal circuits will be calculated as the degree of correlation in activity using a priori defined seeds in ventral and dorsal striatum and regions of interest (ROIs) in ventromedial prefrontal cortex (vmPFC) and pre-supplementary motor area (SMA). FC is measured as continuous Z scores reflecting the correlation of activity between the brain regions. Higher FC Z scores reflect stronger connectivity.
Measured: Baseline, week 2 and 8 post-intervention
Secondary outcomes (5)
Change in Effort Expenditure for Reward (EEfRT)
The EEfRT is a widely used, multi-trial task measuring motivation for rewards as an assessment of anhedonia, as anhedonia is specifically associated with decreased motivation for rewards.
Participants are given an opportunity to choose between two different task difficulty levels in order to obtain monetary rewards by repeated manual button presses within a short time. Button presses raises a virtual ''bar'' viewed onscreen. If they raise the bar to the ''top'' within the prescribed time, they are eligible to win the allotted money. Each trial presents the subject with a choice between two levels of task difficulty, a 'hard task' and an 'easy task' and 3 probabilities of winning. Subjects participate in the task for 20 minutes and the first 50 trials are analyzed by calculating proportion of hard-task choices across each level of probability. Lower proportions of hard task choices indicate decreased motivation.
Measured: Baseline, 2, 4 and 8 weeks post-intervention
Change in Finger Tapping Task (FTT)
This task uses a specially adapted tapper that the subject is asked to tap as fast as possible using the index finger. The subject is given 5 consecutive 10-second trials for both the preferred and non-preferred hands. The finger tapping score is the mean of the 5 trials and is computed for each hand.
A lower score indicates motor impairment.
Measured: Baseline, 2, 4 and 8 weeks post-intervention
Change in Trail Making Tests A (TMT)
In Trail Making Test (TMT) Part A, the participant is tasked with drawing a continuous line connecting a series of 25 numbered circles in ascending order, from 1 to 25. This part of the test primarily assesses visual attention, processing speed, and visuomotor skills. Scoring is based on the time it takes to complete the task, measured in seconds. Higher scores reflect greater impairment or slower completion time (worse outcome).
Measured: Baseline, 2, 4, and 8 weeks post-intervention
Change in Inventory of Depressive Symptoms Self Report (IDS-SR) Anhedonia Subscale Score
Anhedonia is assessed with a 3-item subscale of the Inventory of Depressive Symptomatology Self-Report (IDS-SR). Items are scored on a 4-point scale from 0 to 3. Total scores for the Anhedonia Subscale range from 0 to 9 with higher scores reflecting greater anhedonia.
Measured: Baseline, 2, 4, 6 and 8 weeks post-intervention
Change in Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C) score
SHAPS-C is a 14-item clinician-administered scale that assesses a patient's ability to experience pleasure, specifically in the context of anhedonia (loss of pleasure) and depression. Consists of 14 questions that the clinician asks the patient, with each question having a set of response categories (e.g., "Strongly Agree," "Agree," "Disagree," "Strongly Disagree"). Answers are scored based on whether the patient agrees or disagrees with the statement, with a score of 1 for disagreement (indicating a difficulty experiencing pleasure) and 0 for agreement. Total scores range from 0-14, with higher scores indicating greater difficulty experiencing pleasure or a higher level of anhedonia.
Measured: Baseline, 2, 4, 6 and 8 weeks post-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2025
- Study start3 Sep 2025
- Primary completionFeb 2030 (estimated)
- Study completionFeb 2030 (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 Emory UniversityThe 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
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Jennifer Felger, Emory University
- Investigators
- Jennifer Felger, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07003997
- Sponsor's protocol ID
- STUDY00009295
- Other IDs
- 1R01MH140180-01, 2025P011694
- Status last verified
- Sep 2026
- First submitted
- 26 May 2025
- Last updated
- 28 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data will be de-identified prior to receipt by the repository, but the information needed to generate a global unique identifier for the NIMH Data Archive (NDA) will also be collected for each subject.
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Janus Kinase (JAK) Signaling in Depression
- ClinicalTrials.gov ID
- NCT07003997
- Acronym / sponsor ID
- STUDY00009295
- Conditions
- Major Depressive Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 3 Sep 2025 (actual)
- Primary completion
- Feb 2030 (estimated)
- Study completion
- Feb 2030 (estimated)
- First posted
- 4 Jun 2025 (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 will test the hypothesis that Janus kinase (JAK) signaling is involved in major depression (MD) with high inflammation by determining whether its inhibition with baricitinib can improve functional connectivity in reward and motor circuits in association with improved motivation and motor function in MD patients enriched for high C-reactive protein (CRP) and anhedonia.
Detailed description
Many people with depression also have high inflammation, which may be a cause of some of their depression symptoms. This study is being done to learn how inflammation affects the brain to cause symptoms of depression like anhedonia, low motivation and motor slowing. This will be tested using a medication called baricitinib that blocks one aspect of inflammation involving Janus kinase (JAK) signaling. The population to be included in this study are patients with depression and symptoms of anhedonia who have high inflammation as determined by a blood test. Patients must also be free of uncontrolled medical illnesses. Patients enrolled in the study will be randomly treated with either baricitinib or a placebo (matching sugar pill) for 8 weeks and assessed for markers of inflammation in the blood and symptoms of depression using self-reported and clinician-guided assessments. In addition, brain scans and computerized testing will be done to measure brain function and levels of motivation and motor speed. Participation in the study will include at least 8 visits over 2-3 months, including screening. Subjects will be recruited from local clinics and from the Atlanta community using social media ads. Approximately 100 subjects will be enrolled for this study to obtain 60 subjects who will be randomized to baricitinib or placebo. Blood and information from the brain scans, computerized testing and assessments of depression will be saved for future use. Consent to participate in the study will be obtained either remotely or in person by a trained staff member.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Baricitinib Arm | Experimental | Drug: BaricitinibBaricitinib at dose of 2 mg (1 tablet) will be dispensed to be taken orally, daily for 8 weeks. For subjects that do not exhibit a clinical response at 4 Weeks (50% reduction in HAM-D scores), the dose will be increased to 4 mg/day (2 tablets/day) as tolerated until end of treatment. |
| Placebo Arm | Placebo comparator | Drug: PlaceboPlacebo will be dispensed to be taken orally, daily for 8 weeks. For subjects that do not exhibit a clinical response at 4 Weeks (50% reduction in HAM-D scores), the dose will be increased to 2 tablets per day. |
Who may qualify
- Ages
- 25 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- willing and able to give written informed consent;
- men or women, 25-55 years of age;
- a primary diagnosis of DSM-V major depression, current, or Bipolar, depressed type as diagnosed by the SCID-V;
- score of >14 on the PHQ-9 from screening and HAM-D score ≥18 for study entry;
- off all antidepressant or other psychotropic therapy (e.g. mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks prior to baseline visit (8 weeks for fluoxetine),
Key exclusion criteria (24 listed)
- history or evidence (clinical and laboratory) of an autoimmune disorder
- history or evidence (clinical or laboratory) of hepatitis B or C infection or human immunodeficiency virus infection;
- history of any type of cancer requiring treatment with more than minor surgery;
- unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination, EKG and laboratory testing);
- significant hematological abnormalities at screening (ANC < 1500, Hgb<10, platelet< 100,000)
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 |
|---|---|---|
| BaricitinibAlso: OlumiantThis small molecule, orally bioavailable agent is an immunosuppressant (a medicine that reduces the activity of the immune system). It works by blocking the action of enzymes known as Janus kinases (JAK). These enzymes play an important role in the processes of inflammation. Patients will receive a dose of 2 mg oral daily. The dose will be increased to 4 mg/day (2 tablets/d of baricitinib) as tolerated for subjects that do not exhibit a clinical response at 4 Weeks (50% reduction in HAM-D scores) until end of treatment. | Drug | Baricitinib Arm |
| PlaceboAlso: Sugar pillA placebo is a sugar pill that has no therapeutic effect and will be administered orally. Participants will receive 1 placebo tablet matching the baricitinib tablet. | Drug | Placebo Arm |
Primary outcome
Change in corticostriatal FC in reward and motor circuits after 2 and 8 weeks of study medication
Time frame: Baseline, week 2 and 8 post-intervention
FC in the corticostriatal circuits will be calculated as the degree of correlation in activity using a priori defined seeds in ventral and dorsal striatum and regions of interest (ROIs) in ventromedial prefrontal cortex (vmPFC) and pre-supplementary motor area (SMA). FC is measured as continuous Z scores reflecting the correlation of activity between the brain regions. Higher FC Z scores reflect stronger connectivity.
5 secondary outcomes
Change in Effort Expenditure for Reward (EEfRT)
Time frame: Baseline, 2, 4 and 8 weeks post-intervention
Change in Finger Tapping Task (FTT)
Time frame: Baseline, 2, 4 and 8 weeks post-intervention
Change in Trail Making Tests A (TMT)
Time frame: Baseline, 2, 4, and 8 weeks post-intervention
Change in Inventory of Depressive Symptoms Self Report (IDS-SR) Anhedonia Subscale Score
Time frame: Baseline, 2, 4, 6 and 8 weeks post-intervention
Change in Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C) score
Time frame: Baseline, 2, 4, 6 and 8 weeks post-intervention
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 28 Sep 2026.
- Individual participant dataSharing planned: Yes. All data will be de-identified prior to receipt by the repository, but the information needed to generate a global unique identifier for the NIMH Data Archive (NDA) will also be collected for each subject.
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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.
Jennifer Felger, PhD principal investigator
Emory University
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 Baricitinib in people with Major Depressive Disorder, 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 7 inclusion and 24 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 28 Sep 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 Jennifer Felger, PhD (404-727-3987, jfelger@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in corticostriatal FC in reward and motor circuits after 2 and 8 weeks of study medication (time frame: Baseline, week 2 and 8 post-intervention). 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 28 Sep 2026.