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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Andrew H Miller, MD | Contact | 404-727-8260 | amill02@emory.edu |
| Name | Affiliation | Role |
|---|---|---|
| Andrew H Miller, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory Clinic, Emory University Hospital | Atlanta | Georgia | 30322 | United States | ||
| Emory School Of Medicine |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D019954 | Neurobehavioral Manifestations |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C000596027 | baricitinib |
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| 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.
| 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 |
| Atlanta |
| Georgia |
| 30322 |
| United States |
| Emory University | Atlanta | Georgia | 30329 | United States |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010335 | Pathologic Processes |