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JAK Signaling in Depression

ConditionMajor Depressive Disorder
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age25-55
SponsorEmory University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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);

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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. The dose will be increased to 4 mg/day (2 tablets/d of baricitinib) as tolerated for subjects that do not exhibit a clinical response at 4 Weeks (50% reduction in HAM-D scores) until end of treatment.

  • 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.

Treatment groups

100 Participants
are divided into 2 treatment groups
Group A: Baricitinib ArmExperimental treatment 1 intervention
Group B: Placebo ArmPlacebo comparator 1 intervention

Trial outcomes

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.

Time frame
Baseline, week 2 and 8 post-intervention

Secondary outcomes

1

Change in Effort Expenditure for Reward (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 raises 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 proportion of hard-task choices across each level of probability. Lower proportions of hard task choices indicate decreased motivation.

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

Change in Finger Tapping Task (FTT)

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. A lower score indicates motor impairment.

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

Change in Trail Making Tests A (TMT)

In Trail Making Test (TMT) Part A, the participant is tasked with drawing a continuous line connecting a series of 25 numbered circles in ascending order, from 1 to 25. This part of the test primarily assesses visual attention, processing speed, and visuomotor skills. Scoring is based on the time it takes to complete the task, measured in seconds. Higher scores reflect greater impairment or slower completion time (worse outcome).

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

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

Anhedonia is assessed with a 3-item subscale of the Inventory of Depressive Symptomatology Self-Report (IDS-SR). Items are scored on a 4-point scale from 0 to 3. Total scores for the Anhedonia Subscale range from 0 to 9 with higher scores reflecting greater anhedonia.

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Emory University

Lead sponsor

National Institute of Mental Health (NIMH)

Collaborator

Source ClinicalTrials.gov
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