JAK Signaling in Depression

Launched by EMORY UNIVERSITY · May 26, 2025

Keywords

ClinConnect Summary

This clinical trial, titled "JAK Signaling in Depression," is investigating how a medication called baricitinib, which inhibits a specific signaling pathway in the body (known as JAK signaling), can help improve symptoms in adults with major depression, particularly those experiencing high levels of inflammation. Researchers want to see if this treatment can enhance brain connections related to reward and movement, ultimately improving motivation and physical function for participants who have high inflammation markers, specifically a substance called C-reactive protein (CRP).

To be eligible for the study, participants need to be between 25 and 55 years old, diagnosed with major depression or a specific type of bipolar disorder, and not currently taking any antidepressants or similar medications for at least a month. Participants should also show signs of depression and anhedonia, which means they have trouble feeling pleasure. The study is not yet recruiting, but if you or someone you know might qualify, it could be an opportunity to receive potential new treatment while contributing to important research on depression.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. willing and able to give written informed consent;
• • 2. men or women, 25-55 years of age;
• • 3. a primary diagnosis of DSM-V major depression, current, or Bipolar, depressed type as diagnosed by the SCID-V;
• • 4. score of \>14 on the PHQ-9 from screening and HAM-D score ≥18 for study entry;
• • 5. 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),
• • 6. CRP ≥3 mg/L,
• • 7. PHQ-9 anhedonia score ≥2.
• Exclusion Criteria:
• • 1. history or evidence (clinical and laboratory) of an autoimmune disorder
• • 2. history or evidence (clinical or laboratory) of hepatitis B or C infection or human immunodeficiency virus infection;
• • 3. history of any type of cancer requiring treatment with more than minor surgery;
• • 4. unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination, EKG and laboratory testing);
• • 5. significant hematological abnormalities at screening (ANC \< 1500, Hgb\<10, platelet\< 100,000)
• • 6. history of progressive multifocal leukoencephalopathy,
• • 7. history of deep venous thrombosis,
• • 8. history of cardiovascular disease (coronary artery disease, congestive heart failure, stroke - controlled hypertension is OK),
• • 9. major surgery within 8 weeks prior to screening or will require major surgery during the study,
• • 10. current or recent (\<4 weeks prior to randomization) viral (including COVID-19), bacterial, fungal, or parasitic infection or any other active or recent infection,
• • 11. symptomatic herpes zoster infection at or within 12 weeks of randomization,
• • 12. history of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement),
• • 13. cirrhosis of the liver from any cause,
• • 14. 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),
• • 15. chronic kidney disease with eGFR \<60 mL/min/1.73 m2,
• • 16. 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);
• • 17. 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);
• • 18. history of a cognitive disorder or traumatic head injury involving loss of consciousness;
• • 19. pregnancy or lactation,
• • 20. use of gender affirming hormone therapy;
• • 21. 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;
• • 22. any contraindication for MRI scanning;
• • 23. failure of more than 2 antidepressant trials (at least 6 weeks at recommended dose) in the current episode or 5 antidepressant trials lifetime; and
• • 24. 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.