JAK Signaling in Depression and Cognition in Male Football Players (JAK DC in Play)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Depressive Symptoms; Cognitive Symptom
• Intervention / Treatment: Drug: Baricitinib

Detailed Description

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 football. This will be assessed using a medication called baricitinib that blocks one aspect of inflammation.

This study will enroll depressed adult male football players enriched for high inflammation [blood levels of C-reactive protein (CRP)], anhedonia, and cognitive dysfunction.

Qualifying participants will be asked to take the study medication once daily by mouth for 8 weeks and undergo MRI scans, provide blood and urine samples for safety or to measure biomarkers of inflammation, complete clinician-rated and self-report assessments of depressive and cognitive symptoms, and perform computer or paper-and-pencil tests of neurocognitive function. Blood and other biological samples may be stored for future research use, with the participant's consent.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Andrew H Miller, MD; Phone Number: 404-727-8260; Email: amill02@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University
    • Atlanta, Georgia, United States, 30322
      • Emory Clinic, Emory University Hospital
    • Atlanta, Georgia, United States, 30322
      • Emory School Of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• willing and able to give written informed consent
• males
• >10 years of playing football (at least 1 year in the NFL)
• 40-55 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

Exclusion Criteria:

• 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
• Additional exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Baricitinib; 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; 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.; Other Names: Olumiant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effort-Expenditure for Rewards Task (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 raise 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 the proportion of hard-task choices across each level of probability. Lower proportions of hard task choices indicate decreased motivation.	Baseline and weeks 2, 4 and 8 post-intervention
Finger Tapping Test (FTT)	The Finger Tapping Test (FTT) is a simple neuropsychological assessment that measures fine motor speed, coordination, and nervous system health. 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. Normal/Average: 45-60 taps. Mild Slowing / Potential Impairment: 30-45 taps. Significant Motor Impairment / Fatigue: Fewer than 30 taps	Baseline and weeks 2, 4 and 8 post-intervention
Trail-Making Test (TMT)	The Trail-Making Test (TMT) is a common neuropsychological assessment measuring processing speed, visual attention, and task-switching ability. The test is typically administered using a paper-and-pencil format (or digital equivalent) and has two primary sections: Part A: Patients connect 25 randomly distributed circles containing numbers in ascending order (1, 2, 3...) as quickly as possible. This measures baseline processing speed, motor speed, and visual scanning. Part B: Patients connect 25 circles containing both numbers and letters, strictly alternating between them in ascending order (1-A-2-B-3-C...). This places a much higher cognitive demand on mental flexibility, set-shifting, and working memory. Evaluators record the total time (in seconds) taken to complete each part. Longer times generally indicate poorer cognitive function.	Baseline and weeks 2, 4 and 8 after baricitinib started
Anhedonia Subscale of the Inventory of Depressive Symptoms-Self Reported (IDSSR)	Anhedonia is assessed with a 3-item subscale of the Inventory of Depressive Symptomatology Self-Report (IDS-SR). Each of the three items is rated on a 4-point severity scale from 0 to 3, where 0 indicates no impairment, and 3 indicates maximum severity. Scores range from 0 to 9, with higher scores reflecting a greater severity of anhedonia, meaning a stronger loss of interest, motivation, and ability to experience pleasure.	Baseline and weeks 2, 4, 6, and 8 post-intervention
Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2A)	BRIEF2A is a standardized rating scale that allows adults and knowledgeable informants (caregivers, adult children, partners/spouses) to rate executive function or self-regulation in that adult's day-to-day setting. Scoring relies on T-scores (Mean = 50, Standard Deviation = 10). < 60 T-score: Within Normal Limits. 60 - 64 T-score: Subclinical difficulties; subtle but generally manageable challenges. 65 - 69 T-score: Mildly elevated; noticeable executive function deficits. 70 - 74 T-score: Moderately elevated; significant executive dysfunction affecting daily life. >= 75 T-score: Highly elevated; severe impairment.	Baseline and weeks 2 and 8 post-intervention
Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C)	The Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C) is a 14-item validated clinician-administered assessment tool used to measure hedonic capacity and evaluate anhedonia (the inability to experience pleasure). The clinician asks the patient about their expected or actual ability to feel pleasure over the past few days, translating the standard self-report questions into a guided clinical interview. Responses are typically evaluated using a 4-point Likert scale (Strongly Disagree, Disagree, Agree, Strongly Agree). Total scores range from 0 to 14, with higher scores indicating greater difficulty experiencing pleasure or a higher level of anhedonia.	Baseline and weeks 2, 4, 5, 6, and 8 after baricitinib started
Hamilton Depression (HAM-D) Rating Scale	Hamilton Depression (HAM-D) Rating Scale is the most widely used clinician-administered depression assessment scale. It evaluates symptoms such as mood, guilt, insomnia, anxiety, and weight loss over the previous week. Scores are tallied to estimate the severity of the depression, although context and clinical judgment are always required. Maximum score is 52 0 to 7: Normal/Remission 8 to 16: Mild Depression 17 to 23: Moderate Depression 24 or higher: Severe Depression	Baseline and weeks 2, 4, 5, 6, and 8 post-intervention
Columbia Suicide Severity Rating Scale (CSSR)	The Columbia-Suicide Severity Rating Scale (C-SSRS) evaluates both suicidal ideation and suicidal behavior. Minimum 0 (no ideation) to Max: 5 (active suicidal ideation with a specific plan and intent). Meaning of Scores:0: No suicidal ideation reported.; (Wish to be Dead): Endorses thoughts about a wish to be dead or not alive.; (Non-Specific Thoughts): General, non-specific thoughts of wanting to end life, without methods or plans.; (Method, No Intent/Plan): Thoughts of suicide with a specific method in mind, but no intent or actual plan to act.; (Some Intent, No Plan): Thoughts of suicide and some intent to act, but without fully mapped-out details.; (Specific Plan and Intent): Fully or partially worked-out details of a suicide plan with intent to carry it out.	Baseline and weeks 2, 4, 5, 6, and 8 post-intervention
Phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3)	Intracellular pSTAT3 in peripheral blood immune cells will be assessed by flow cytometric methods.	Baseline and weeks 2 and 8 post-intervention
Plasma inflammatory biomarkers	CRP, IL-6, TNF-alpha and IL-1beta. High-sensitivity (hs) CRP will be assayed using an immunoturbidometric assay with a Beckman AU480 chemistry analyzer and Ultra WR CRP kit (Sekisui Diagnostics). Inflammatory cytokines (IL-1, IL-6, TNF) and their soluble receptors will be analyzed by multiplex bead-based assays, previously validated against individual ELISA.	Baseline and weeks 2 and 8 post-intervention

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Andrew H Miller, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; Football player; NFL
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Behavioral Symptoms; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Depression; Inflammation; Neurobehavioral Manifestations; baricitinib
• Other Study ID Numbers: 2026P000577

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes