NCT05849038 · Emory University
Inflammation and Depression in People With HIV
What this study is about
The purpose of this 10-week, where neither patients nor doctors know which treatment is given, compared against an inactive treatment study is to determine whether inflammation impacts reward and motor neural circuitry to contribute to depressive symptoms like anhedonia and psychomotor slowing in people with Human Immunodeficiency Virus (HIV) and depression.
View original scientific description
The purpose of this 10-week, double-blind, placebo-controlled study is to determine whether inflammation impacts reward and motor neural circuitry to contribute to depressive symptoms like anhedonia and psychomotor slowing in people with Human Immunodeficiency Virus (HIV) and depression.
Interventions
DRUG
Baricitinib
Patients will receive baricitinib at a dose of 2 mg oral daily.
OTHER
Placebo
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.
Primary outcome measures
Change in corticostriatal functional connectivity (FC) in reward circuit
Time frame: Baseline visit, week 2, and week 10 after study medication
Patients will undergo resting-state and task-based functional magnetic resonance imaging (fMRI) to calculate functional connectivity (FC) between the ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC). FC is measured as continuous Z scores reflecting the correlation of activity between the brain regions. Higher FC Z scores reflect stronger connectivity.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- HIV infected on continuous antiretroviral therapy (ART) with plasma HIV RNA \<200 copies/ml for at least 12 months (on at least two previous clinic visits and confirmed at screening)
- Current cluster of differentiation 4 (CD4+) \> 350 cells/microliter for at least twelve months (on at least two previous clinic visits and confirmed at screening)
- A primary diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) major depression, current, or Bipolar, depressed type as diagnosed by the SCID-V
- Score of ≥10 on the 9-item Patient Health Questionnaire (PHQ-9)
- Off all antidepressant or other psychotropic therapy (e.g. mood stabilizers, antipsychotics, and sedative hypnotics) for at least 4 weeks (8 weeks for fluoxetine) or on a stable psychotropic regimen for at least 4 weeks prior to baseline visit
- Significant anhedonia as reflected by a score ≥ 2 on item #1 of the PHQ-9
- Women of reproductive age will have a negative serum pregnancy test at study entry and both men and women must agree to adequate contraception while
Exclusion criteria
- \< 18 years of age or \> 65 years of age
- Pregnancy or breastfeeding
- Significant hematological abnormalities at screening (ANC \< 1500, Hgb\<10, platelet\< 100,000)
- History of progressive multifocal leukoencephalopathy
- Untreated latent tuberculosis infection (which will be screened for prior to entry)
- Having taken the following immunosuppressive medications within the past 6 months:
- Oral corticosteroids
- Biologic treatments such as etanercept, infliximab, certolizumab, adalimumab, golimumab, tocilizumab, abatacept, Ustekinumab, ixekizumab, secukinumab, or anakinra
- Cyclophosphamide (or any other cytotoxic agent), belimumab, or anifrolumab (or another anti-interferon (IFN) therapy)
- Rituximab, any other B cell depleting therapies, or intravenous immunoglobulin (IVIg)
- any Janus kinase (JAK) inhibitor
- History of deep venous thrombosis
- Cardiovascular disease:
- Coronary artery disease or history of myocardial infarction
- Congestive heart failure with left ventricular ejection fraction ≤40% per American Heart Association guidelines
- Stroke history
- Hematologic malignancies including lymphoma and leukemia
- Major surgery within 8 weeks prior to screening or will require major surgery during the study
- Current or recent (\<4 weeks prior to randomization) clinically serious viral (including coronavirus disease 2019 (COVID-19)), bacterial, fungal, or parasitic infection or any other active or recent infection
- Symptomatic herpes simplex at the time of randomization
- Symptomatic herpes zoster infection within 12 weeks prior to randomization
- History of disseminated/complicated herpes zoster (for example, ophthalmic zoster or CNS involvement)
- Positive test for hepatitis B virus (HBV) defined as:
- positive for hepatitis B surface antigen (HBsAg), or
- positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B virus deoxyribonucleic acid (HBV DNA)
- Hepatitis C virus (HCV) infection (hepatitis C antibody-positive and HCV ribonucleic acid \[RNA\]-positive)
- Cirrhosis of the liver from any cause
- Any of the following specific abnormalities on screening laboratory tests:
- alanine transaminase (ALT) or aspartate aminotransferase (AST) \>2 x upper limits of normal (ULN)
- alkaline phosphatase (ALP) ≥2 x ULN
- total bilirubin ≥1.5 x ULN (with the exception of patients on atazanavir, who must have total bilirubin \<2 x ULN)
- Chronic kidney disease with estimated glomerular filtration rate (eGFR) \<40 mL/min/1.73 m\^2
- History of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; substance abuse/dependence within 6 months of study entry, as determined by severe combined immunodeficiency (SCID)
- A positive urine drug screen for illicit drugs at any time during the study excluding marijuana
- An active suicidal plan as determined by a score \>3 on item #3 on the Hamilton Rating Scale for Depression (HAM-D)
- An active eating disorder or antisocial personality disorder
- History of dementia
- Chronic use of glucocorticoid containing medications or minocycline within 2 weeks of baseline or at any time during the study
- Any contraindication for MRI scanning
- Failure of more than 2 antidepressant trials (at least 6 weeks at recommended dose) in the current episode or 5 antidepressant trials lifetime
- BMI \>42 (to exclude severe obesity) or at the investigator's discretion based on the patient's ability to fit in the MRI scanner
Where
- Atlanta, Georgia
Collaborators
National Institute of Mental Health (NIMH)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 28, 2026 · Source of record for eligibility and locations