Inflammation and Depression in People With HIV

• Status: Not yet recruiting
• Trial end date: 2027-11-01
• Target enrollment: 0
• Participant gender: All

Summary

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. Sixty male and female patients with HIV who have depression, anhedonia and high inflammation and are stable on effective treatment for their HIV will be randomized to receive either the anti-inflammatory drug baricitinib or a placebo for 10 weeks. Participants will complete lab tests, medical and psychiatric assessments, neurocognitive testing, functional MRI (fMRI) scans, and optional spinal taps as part of the study. The total length of participation is about 5 months.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Emory University
• Collaborator: National Institute of Mental Health (NIMH)

Criteria

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 CD4+ > 350 cells/microliter for at least twelve months (on at least two previous clinic visits and confirmed at screening).

• A primary diagnosis of DSM-V major depression, current, or Bipolar, depressed type as diagnosed by the SCID-V.

• Score of ≥15 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.

• CRP≥3mg/L.

• Women of reproductive age will have a negative serum pregnancy test at study entry and agree to contraception while on study drug.

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)

• Immunosuppressive medications (including corticosteroids) and anticoagulants (aspirin acceptable)

• History of deep venous thrombosis

• Cardiovascular disease:

1. Coronary artery disease or history of myocardial infarction

2. Congestive heart failure with left ventricular ejection fraction ≤40% per American Heart Association guidelines152

3. 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 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:

1. positive for hepatitis B surface antigen (HBsAg), or

2. 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:

1. ALT or AST >2 x upper limits of normal (ULN)

2. alkaline phosphatase (ALP) ≥2 x ULN

3. 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 eGFR <40 mL/min/1.73 m2 (note that dose of baricitinib will be reduced to 1 mg daily in participants with GFR between 40 and 60).

• 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.

• <24 on the Mini-Mental State Exam.

• Chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), 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 >40 (to exclude severe obesity).

• History of an autoimmune disorder