JAK Signaling in Depression and Cognition in Male Football Players

NCT07608796 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2026P000577
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

This study is being done to learn more about the role of inflammation in depressive and cognitive symptoms in patients with depression who have played at least 10 years of organized football. This will be evaluated using a medication called baricitinib that blocks one aspect of inflammation.

Conditions

Depressive Symptoms; Cognitive Symptom

Keywords

Football player; Inflammation; NFL

Outcome Measures

Primary Outcomes (1)

• Monetary Incentive Delay (MID) Task functional magnetic resonance imaging (fMRI)

  Resting-state and task-based MID Task functional magnetic resonance imaging (fMRI). The MID Task is a specialized behavioral paradigm used during functional magnetic resonance imaging (fMRI). It isolates and measures the neural mechanisms of reward processing, specifically motivational salience, anticipation, and outcome feedback. fMRI blood oxygen level-dependent (BOLD) for resting and task-based functional connectivity: A multi-echo (ME) ep2 BOLD sequence will be optimized to provide a high signal-to-noise ratio in regions of interest that is maintained during minor incidences of head motion. Resting ME BOLD will be acquired over \~10 min, and task fMRI will involve two \~10 min scans. For resting bold, a single acquisition of phase-encoding in the opposite polarity (anterior-posterior) for distortion correction over \~30 seconds.

  Baseline and weeks 2 and 8 post-intervention

Secondary Outcomes (10)

• Effort-Expenditure for Rewards Task (EEFRT)

  Baseline and weeks 2, 4 and 8 post-intervention

• Finger Tapping Test (FTT)

  Baseline and weeks 2, 4 and 8 post-intervention

• Trail-Making Test (TMT)

  Baseline and weeks 2, 4 and 8 after baricitinib started

• Anhedonia Subscale of the Inventory of Depressive Symptoms-Self Reported (IDSSR)

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

• Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2A)

  Baseline and weeks 2 and 8 post-intervention

Study Arms (1)

Baricitinib

EXPERIMENTAL

Participants will receive 1 tablet/d of 2 mg baricitinib at baseline. For participants who do not exhibit a clinical response at 4 Weeks (a 50% reduction in HAM-D scores), the dose will be increased to 4 mg/day (2 tablets/d of baricitinib), as tolerated.

Drug: Baricitinib

Interventions

Baricitinib DRUG

Baricitinib is an orally administered, selective inhibitor of Janus kinase (JAK) 1 and 2. It reduces cytokine-mediated signaling involved in inflammation and immune activation. Baricitinib is FDA-approved for rheumatoid arthritis (RA), atopic dermatitis, and alopecia areata. It has also been authorized for the treatment of COVID-19 in hospitalized patients. Baricitinib will be dispensed every other week at the Week 2, 4, and 6 study visits. Participants who do not exhibit a clinical response (50% reduction in HAM-D scores from baseline) at Week 4 will be increased to 4 mg/day of baricitinib (2 x 2 mg tablets). A virtual follow-up visit will be conducted at Week 1 to assess safety and tolerability in all patients, and at Week 5 in patients who increase the dose.

Also known as: Olumiant

Baricitinib

Eligibility Criteria

• Age: 40 Years - 55 Years
• Gender Eligibility Details: Given that no women play football in the NFL at this time, women will not be included in this study. Males with a history of playing football for at least 10 years, including 1 year in the NFL
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• willing and able to give written informed consent
• males
• \>10 years of playing football (at least 1 year in the NFL)
• years of age
• Current Diagnostic and Statistical Manual (DSM)-V major depression or Bipolar, depressed type; or DSM-V major depression or Bipolar, depressed type in partial remission as diagnosed by the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID)-V
• score of \>10 on the PHQ-9 from screening and HAM-D score ≥16 for study entry
• off all antidepressant or other psychotropic therapy (e.g., mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks before baseline visit (8 weeks for fluoxetine) or on a stable psychotropic regimen for at least 4 weeks (and no planned changes)
• CRP ≥3 mg/L
• PHQ-9 anhedonia (item #1) and cognitive (item #7) scores ≥2

You may not qualify if:

• current or history of past 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 6 months before screening, or will require major surgery during the study
• current or recent (\<4 weeks before study start) 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 study start
• history of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement)
• cirrhosis of the liver from any cause

Sponsors & Collaborators

• Emory University: lead

Study Sites (3)

Emory Clinic, Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Emory School Of Medicine

Atlanta, Georgia, 30322, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

MeSH Terms

Conditions

Depression; Neurobehavioral Manifestations; Inflammation

Interventions

baricitinib

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Study Officials

• Andrew H Miller, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew H Miller, MD

CONTACT

404-727-8260; amill02@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: May 27, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)