Baricitinib for Depression in People With HIV

Recruiting at 2 trial locations

Overseen By Jennifer Felger, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must be taking: Antiretroviral therapy

Must not be taking: Immunosuppressants, NSAIDs, JAK inhibitors

Disqualifiers: Age, Pregnancy, Cardiovascular disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 10

Duration: 10 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether reducing inflammation can improve symptoms of depression, such as lack of interest in activities and slow movements, in people living with HIV. Participants will receive either the anti-inflammatory drug baricitinib (also known as Olumiant or LY3009104) or a placebo for 10 weeks. Lab tests, brain scans, and other assessments will track changes. The trial is suitable for individuals living with HIV who are on stable HIV treatment and experience significant depression and inflammation. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you either stop taking antidepressants or other psychotropic medications (like mood stabilizers or antipsychotics) for at least 4 weeks before starting, or be on a stable dose for at least 4 weeks. If you're taking fluoxetine, you need to stop it for 8 weeks before starting the trial.

Is there any evidence suggesting that baricitinib is likely to be safe for humans?

Research has shown that baricitinib has been studied for safety in individuals with conditions like HIV and depression. The FDA has already approved baricitinib for other uses, indicating it has passed safety tests for those conditions.

In earlier studies, baricitinib showed potential in reducing inflammation, which is crucial for people with HIV. These studies also explored whether baricitinib could address hidden HIV in the body. The research involved adults with HIV, focusing on both safety and effectiveness.

While researchers are exploring new uses for baricitinib, its existing approval for other conditions can reassure about its safety. Always consult a healthcare provider to understand the risks and benefits specific to your health situation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Baricitinib is unique because it offers a new approach to treating depression in people with HIV by targeting the immune system. Unlike standard antidepressants that primarily focus on neurotransmitter levels, baricitinib is a JAK inhibitor, which reduces inflammation that might contribute to depression. Researchers are excited because this novel mechanism could provide relief for those who don't respond to traditional treatments, offering hope for improved mental health outcomes in this specific population.

What evidence suggests that baricitinib might be an effective treatment for depression in people with HIV?

Research has shown that baricitinib, a drug that reduces inflammation, might help lessen depression symptoms in people with HIV. In this trial, participants will receive either baricitinib or a placebo for 10 weeks. Studies indicate that baricitinib effectively decreases inflammation, which is believed to contribute to depression. By reducing inflammation, brain functions related to pleasure and movement might improve, potentially alleviating symptoms like loss of interest in activities and slowed thinking or movement. This medication is already approved for other conditions, suggesting it is likely safe. While more research is needed, early evidence supports its potential to help with depression in individuals with high inflammation. ^{1 2 3 5 6}

Who Is on the Research Team?

Andrew H Miller, MD

Principal Investigator

Emory University

Jennifer Felger, PhD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for men and women with HIV who are stable on treatment, have depression with significant anhedonia (lack of pleasure including low motivation or feeling like everything is an effort), and high inflammation. They must not be pregnant or breastfeeding, should agree to use contraception, have a CD4+ count over 350, no major health issues like heart failure or untreated infections, and not be on certain medications.

Inclusion Criteria

You have been diagnosed with HIV

Have you been on stable antiretroviral therapy (ART) regimen for more than 1 year?

Have you been diagnosed with HIV?

Exclusion Criteria

Are you pregnant, actively trying to become pregnant, or are you breastfeeding?

Do you have any reason you cannot have an MRI scan (e.g. pacemaker)?

Have you ever been diagnosed or treated for an autoimmune disorder or cancer (excluding skin cancer)?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the anti-inflammatory drug baricitinib or a placebo for 10 weeks

10 weeks

Baseline visit and week 10 visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Baricitinib
• Placebo

Trial Overview The study tests if the anti-inflammatory drug baricitinib affects depressive symptoms in people with HIV compared to a placebo. Participants will undergo medical assessments, neurocognitive testing, brain scans (fMRI), and optional spinal taps over approximately 3.5 months.

How Is the Trial Designed?

Group I: Baricitinib Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Baricitinib is already approved in United States, European Union for the following indications:

Approved in United States as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Approved in European Union as Olumiant for:

• Rheumatoid arthritis
• Severe alopecia areata
• COVID-19

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In a study of 881 HIV-infected veterans, 46% exhibited significant depressive symptoms, but these symptoms did not correlate with illness severity or survival rates after adjusting for HIV symptoms.

HIV symptoms were found to be significantly associated with both the severity of illness and survival, indicating that healthcare providers should prioritize addressing HIV symptoms independently of any depressive symptoms present.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical importance of HIV and depressive symptoms among veterans with HIV infection. Kilbourne, AM., Justice, AC., Rollman, BL., et al.[2019]

The study involved 304 HIV-infected adults with major depressive disorder and tested a measurement-based care (MBC) intervention, which led to significant improvements in depressive severity and increased depression-free days, although it did not enhance antiretroviral adherence or other HIV outcomes.

Participants in the MBC group experienced a clinically significant reduction in depressive symptoms and a higher rate of depression remission compared to usual care, suggesting that integrating depression management into HIV care can effectively reduce depression morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of antidepressant treatment on HIV and depression outcomes: results from a randomized trial. Pence, BW., Gaynes, BN., Adams, JL., et al.[2022]

Among HIV-infected individuals on Medicaid, women were more likely to be diagnosed with depression, while African Americans were less likely, highlighting disparities in mental health diagnosis.

Depressed patients receiving antidepressant treatment not only had better access to antiretroviral therapy but also experienced a 24% reduction in monthly healthcare costs compared to those not treated with antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant treatment and health services utilization among HIV-infected medicaid patients diagnosed with depression. Sambamoorthi, U., Walkup, J., Olfson, M., et al.[2019]

HIV infection, despite improved life expectancy due to HAART, can lead to significant neurological disturbances, with depression being the most common neuropsychiatric disorder among patients, affecting their quality of life and adherence to treatment.

The mechanisms by which HIV predisposes individuals to depression include chronic inflammation, neurotoxicity, and reduced levels of brain-derived neurotrophic factor, highlighting the need for targeted pharmacological treatments to address these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human immunodeficiency virus-associated depression: contributions of immuno-inflammatory, monoaminergic, neurodegenerative, and neurotrophic pathways. Del Guerra, FB., Fonseca, JL., Figueiredo, VM., et al.[2021]

Patients with HIV should be routinely screened for major depression, as accurate diagnosis is crucial to avoid harmful exposure to inappropriate psychotropic medications.

Antidepressants used to treat major depression in HIV-infected patients are similar to those used in the general population, and while no specific antidepressant is superior, patient adherence is key, influenced by the side effects of these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment of depression in HIV-positive patients : safety considerations. Pieper, AA., Treisman, GJ.[2022]

The 10-item CES-D scale has been shown to be a reliable and valid tool for measuring depressive symptoms in HIV-positive patients, with a high correlation (0.97) to the original 20-item scale.

This shortened scale demonstrated excellent internal consistency (Cronbach α=0.88) and predictive accuracy, with sensitivity at 91% and specificity at 92%, making it effective for identifying depression in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validating a shortened depression scale (10 item CES-D) among HIV-positive people in British Columbia, Canada. Zhang, W., O'Brien, N., Forrest, JI., et al.[2022]

Antidepressant medications have been found to be effective in treating depression among HIV-positive individuals, with a pooled effect size of 0.57 based on a systematic review of 7 studies involving 494 subjects.

However, the studies showed significant variability in results, largely influenced by placebo responses, and highlighted a concerning lack of representation of women and minorities, suggesting that future research should focus on these underrepresented groups to improve generalizability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of antidepressant medication among HIV-positive individuals with depression: a systematic review and meta-analysis. Himelhoch, S., Medoff, DR.[2022]

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05849038/inflammation-and-depression-in-people-with-hiv?q=baricitinib

Inflammation and Depression in People With HIV Thus, the key hallmark of the efficacy of baricitinib in human studies across disease states is its ability to significantly reduce plasma ...

2. withpower.com withpower.com/trial/phase-2-anhedonia-5-2023-86924

Baricitinib for Depression in People With HIV Antidepressant medications have been found to be effective in treating depression among HIV-positive individuals, with a pooled effect size of 0.57 based on a ...

3. ema.europa.eu ema.europa.eu/en/documents/rmp/olumiant-epar-risk-management-plan_en.pdf

Olumiant, INN-baricitinib - European Medicines Agency 2013). • 8.8% had signs of major depressive episode [US] (Koo et al. 1994). • 2.9% depression diagnosed by electronic records [Taiwan] (Chu et ...

4. ctv.veeva.com ctv.veeva.com/study/inflammation-and-depression-in-people-with-hiv

Inflammation and Depression in People With HIV This study will utilize an FDA-approved medication, baricitinib, to establish whether the effects of inflammation on reward and motor circuits ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07209267

NCT07209267 | Baricitinib Curative Repression of HIV-1 The goal is to see if baricitinib can safely reduce inflammation and the HIV that is hidden in the body.

6. humanhealth.emory.edu humanhealth.emory.edu/degreesandprograms/gavegnano-drug-discovery-program/focus-on-neurotherapeutics.html

Focus on Neurotherapeutics Evidence suggests that this drug has activity against HIV in the central nervous system (CNS). In our recently completed pilot study, we showed that baricitinib ...