JAK Signaling in Depression and Cognition in Male Football Players

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexMale
Age30-55
SponsorEmory University

About this trial

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 11 years of organized tackle football. This will be evaluated using a medication called baricitinib, which blocks one aspect of inflammation.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

willing and able to give written informed consent

males

playing tackle football for at least 11 years

30-55 years of age

Disqualifiers

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)

Trial design

Design model

Single group

Treatments tested in this trial

  • 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.

Treatment groups

30 Participants
are divided into 1 treatment group
Group A: BaricitinibExperimental treatment 1 intervention

Trial outcomes

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.

Time frame
Baseline and weeks 2 and 8 post-intervention

Secondary outcomes

1

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.

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

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

Time frame
Baseline and weeks 2, 4 and 8 post-intervention
3

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.

Time frame
Baseline and weeks 2, 4 and 8 after baricitinib started
4

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.

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

Other outcomes

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