JAK Signaling in Depression

NCT07003997 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY000092951R01MH140180-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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 patients enriched for high C-reactive protein (CRP) and anhedonia.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, week 2 and 8 post-intervention

Secondary Outcomes (5)

• Change in Effort Expenditure for Reward (EEfRT)

  Baseline, 2, 4 and 8 weeks post-intervention

• Change in Finger Tapping Task (FTT)

  Baseline, 2, 4 and 8 weeks post-intervention

• Change in Trail Making Tests A (TMT)

  Baseline, 2, 4, and 8 weeks post-intervention

• Change in Inventory of Depressive Symptoms Self Report (IDS-SR) Anhedonia Subscale Score

  Baseline, 2, 4, 6 and 8 weeks post-intervention

• Change in Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C) score

  Baseline, 2, 4, 6 and 8 weeks post-intervention

Study Arms (2)

Baricitinib Arm

EXPERIMENTAL

Baricitinib at dose of 2 mg will be dispensed to be taken orally, daily for 8 weeks.

Drug: Baricitinib

Placebo Arm

PLACEBO COMPARATOR

Placebo will be dispensed to be taken orally, daily for 8 weeks.

Drug: Placebo

Interventions

Baricitinib DRUG

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.

Also known as: Olumiant

Baricitinib Arm

Placebo DRUG

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

Placebo Arm

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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,
• 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,

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

baricitinib; Sugars

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Carbohydrates

Study Officials

• Jennifer Felger, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Felger, PhD

CONTACT

404-727-3987; jfelger@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 26, 2025
• First Posted: June 4, 2025
• Study Start: September 3, 2025
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: The research community will have access to data at the end of the grant award or when a publication has been submitted. Once the data are submitted to NDA, that archive will control the long-term persistence of the data set. Currently, NDA has no process for deleting or retiring data sets.
• Access Criteria: Data will be findable for the research community through the NDA Collection that will be established when this application is funded. To request access of the data, researchers will use the standard processes at NDA, and the NDA Data Access Committee will decide which requests to grant. The standard NDA data access process allows access for one year and is renewable.

Locations

US (1)