RightFit
RecruitingPhase 2

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 65 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: MRI scans, Spinal tap (lumbar puncture)

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Participants will complete lab tests, medical and psychiatric assessments, neurocognitive testing, functional MRI (fMRI) scans, and optional spinal taps as part of the study."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This 10-week study tests whether inflammation affects brain activity linked to depression in people with HIV. It compares baricitinib, a drug that lowers inflammation, with a placebo, a pill with no active drug. It is for people whose HIV is well controlled and who have depression, trouble enjoying things, and high inflammation.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Take HIV medicine without breaks, with HIV levels below 200 copies/mL for at least 12 months.
  • Have a CD4 count, a measure of immune cells, above 350 cells/microliter for at least 12 months.
  • Have current major depression or bipolar disorder with depression.
  • Score at least 10 on the PHQ-9 depression survey.
  • Be off mental health medicines for at least 4 weeks, or 8 weeks for fluoxetine, or have a steady medicine plan for at least 4 weeks before the first visit.
  • Have trouble enjoying things, with a score of at least 2 on the first PHQ-9 question.
  • Have a CRP blood test result of at least 2 mg/L, showing inflammation.
  • Women who can become pregnant must have a negative blood pregnancy test at study entry. Both men and women must agree to use birth control.

Who can't join

  • Be younger than 18 or older than 65; be pregnant or breastfeeding; or have a BMI above 42, a measure of body size, or be unable to safely have or fit in an MRI scan.
  • Have certain low blood cell counts, blood cancers, a past deep-vein blood clot, heart artery disease, a past heart attack or stroke, or heart failure with poor pumping.
  • Have untreated inactive tuberculosis, a past brain infection called PML, a current or recent infection, active herpes symptoms, recent shingles, or past shingles that spread or caused serious problems.
  • Have certain positive hepatitis B tests, active hepatitis C, severe liver scarring, certain abnormal liver tests, or kidney disease with a filtering rate below 40.
  • Have used certain medicines that weaken the immune system in the past 6 months; or regularly use steroid medicines or minocycline within 2 weeks before the first visit or during the study.
  • Have major surgery within 8 weeks before screening or need major surgery during the study.
  • Have certain disorders involving loss of touch with reality, current symptoms of this kind, recent substance misuse, a positive illegal-drug test other than marijuana, an active suicide plan, an active eating disorder, antisocial personality disorder, or dementia.
  • Have more than 2 antidepressant treatments fail during the current depression episode, after at least 6 weeks at the recommended dose, or have 5 antidepressant treatments fail over your lifetime.

Simplified for readability. The official criteria below are what the study team uses.

Official 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 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: 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 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

Study sites (2)

GA