Investigating the link between inflammation and depression in people with HIV

The Role of Inflammation in Central Nervous System (CNS) Mechanisms of Anhedonia and Psychomotor Slowing in Depressed People With HIV

This study is testing if an anti-inflammatory drug can help reduce depression symptoms in people with HIV who have high inflammation.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Emory University (Academic / other)
• Drugs / interventions: infliximab, certolizumab, adalimumab, golimumab, tocilizumab, Ustekinumab, ixekizumab, secukinumab, belimumab, anifrolumab, Rituximab, Cyclophosphamide, baricitinib
• Locations: 2 sites (Atlanta, Georgia and 1 other locations)
• Trial ID: NCT05849038 on ClinicalTrials.gov

What this trial studies

This 10-week, double-blind, placebo-controlled study aims to explore how inflammation affects reward and motor neural circuitry, contributing to depressive symptoms such as anhedonia and psychomotor slowing in individuals with HIV. Sixty participants, both male and female, who are stable on HIV treatment and exhibit high inflammation and depression will be randomized to receive either the anti-inflammatory drug baricitinib or a placebo. The study will involve various assessments, including lab tests, psychiatric evaluations, neurocognitive testing, and functional MRI scans, to gather mechanistic insights into the relationship between inflammation and depression in this population.

Who should consider this trial

Good fit: Ideal candidates include individuals with HIV who are stable on antiretroviral therapy, have a diagnosis of major depression, and exhibit high levels of inflammation.

Not a fit: Patients who are currently on antidepressant or other psychotropic medications may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new therapeutic approaches for managing depression in people living with HIV.

How similar studies have performed: While studies have explored the relationship between inflammation and depression, this specific approach using baricitinib in the context of HIV is novel and has not been extensively tested.

Eligibility 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 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
* CRP≥2mg/L
* Women of reproductive age will have a negative serum pregnancy test at study entry and both mend 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:

  1. Oral corticosteroids
  2. Biologic treatments such as etanercept, infliximab, certolizumab, adalimumab, golimumab, tocilizumab, abatacept, Ustekinumab, ixekizumab, secukinumab, or anakinra
  3. Cyclophosphamide (or any other cytotoxic agent), belimumab, or anifrolumab (or another anti-interferon (IFN) therapy)
  4. Rituximab, any other B cell depleting therapies, or intravenous immunoglobulin (IVIg)
  5. any Janus kinase (JAK) inhibitor
* 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 guidelines
  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 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:

  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. alanine transaminase (ALT) or aspartate aminotransferase (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 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 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 \>42 (to exclude severe obesity) or at the investigator's discretion based on the patient's ability to fit in the MRI scanner

Where this trial is running

Atlanta, Georgia and 1 other locations

• Grady Memorial Hospital — Atlanta, Georgia, United States (Recruiting)
• Emory University Hospital — Atlanta, Georgia, United States (Recruiting)

Study contacts

• Principal investigator: Andrew H Miller, MD — Emory University
• Study coordinator: Jennifer Felger, PhD

Conditions HIV; Depression; Anhedonia; Human Immunodeficiency Virus; Psychomotor Slowing