Inflammation and Depression in People With HIV

NCT05849038 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: STUDY000055265R01MH128872-032025P011788
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

HIV; Depression; Anhedonia

Keywords

Human Immunodeficiency Virus (HIV); Anhedonia; Psychomotor Slowing

Outcome Measures

Primary Outcomes (1)

• Change in corticostriatal functional connectivity (FC) in reward circuit

  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.

  Baseline visit, week 2, and week 10 after study medication

Secondary Outcomes (10)

• Change in Effort Expenditure for Reward Task (EEfRT) Score

  Baseline visit, week 2, and week 10

• Change in Snaith-Hamilton Pleasure Scale-Self Report (SHAPS-SR) Score

  Baseline visit, week 1, week 2, week 4, week 6, and week 10

• Change in Motivation and Pleasure Scale-Self-Report (MAP-SR) Score

  Baseline visit, week 1, week 2, week 4, week 6, and week 10

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

  Baseline visit, week 1, week 2, week 4, week 6, and week 10

• Change in Multidimensional Fatigue Inventory (MFI) Score

  Baseline visit, week 1, week 2, week 4, week 6, and week 10

Study Arms (2)

Baricitinib

EXPERIMENTAL

Participants will be randomized to receive 10 weeks of treatment with baricitinib.

Drug: Baricitinib

Placebo

PLACEBO COMPARATOR

Participants will be randomized to receive 10 weeks of treatment with placebo.

Other: Placebo

Interventions

Baricitinib DRUG

Patients will receive baricitinib at a dose of 2 mg oral daily.

Also known as: Olumiant

Baricitinib

Placebo OTHER

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \< 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

Sponsors & Collaborators

• Emory University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

RECRUITING

Emory University Hospital

Atlanta, Georgia, 30322, United States

RECRUITING

MeSH Terms

Conditions

Depression; Anhedonia; Acquired Immunodeficiency Syndrome; Psychomotor Disorders

Interventions

baricitinib

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Andrew H Miller, MD

  Emory University

  PRINCIPAL INVESTIGATOR

• Jennifer Felger, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jennifer Felger, PhD

CONTACT

404-727-3987; jfelger@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 27, 2023
• First Posted: May 8, 2023
• Study Start: December 11, 2023
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available for sharing after publication of the results from this study.
• Access Criteria: De-identified human subjects data, harmonized to a common standard, are available to qualified researchers. Summary data are available to all.

Locations

US (2)