A Phase 2 interventional study of Baricitinib and Placebo in Major Depressive Disorder, sponsored by Emory University. Recruiting at 1 site in United States. Open to participants aged 25 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-09-28.
Sponsored by Emory University · Phase 2, Interventional, and Treatment
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.
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.
Exclusion Criteria:
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.
Drug: Baricitinib
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.
Drug: Placebo
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.
Also known as: Olumiant
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.
Also known as: Sugar pill
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.
Time frame: Baseline, week 2 and 8 post-intervention
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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: Baseline, 2, 4, 6 and 8 weeks post-intervention
Plan to share: 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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