Clinical trial NCT02272946: Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
Official title: Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV
Cardiovascular Disease
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
First posted: 2014-10-23
Enrollment: 43
Sex: ALL
Minimum age (years): 40
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effects of IL-1β inhibition on safety, measures of systemic and vascular inflammation and endothelial function (all indicators of cardiovascular risk) in treated and suppressed HIV infected individuals This study will assess the safety and effects of canakinumab on endothelial function (assessed by flow-mediated vasodilation \[FMD\] of the brachial artery), vascular inflammation (assessed by FDG-PET/CT scanning), key inflammatory markers of cardiovascular disease (CVD) risk (high-sensitivity C-reactive protein \[hsCRP\]), interleukin-6 (IL-6), soluble CD163 (sCD163), D-dimer, T-cell and monocyte activation in the blood, and size of the HIV reservoir. 10 individuals will receive a single dose of 150mg canakinumab with follow-up for 12 weeks. In the second part of the study, 100 participants will be randomized (2:1 - canakinumab to placebo) and will be followed by for 36 weeks.


Eligibility criteria: Inclusion Criteria:

1. HIV infection,
2. Age ≥ 40 years \< 60 years
3. On continuous ART for at least 12 months with no change in regimen in 12 weeks prior to study entry
4. CD4+ T cell count ≥ 400 cells/mm3
5. HIV RNA level below the standard limit of quantification for 52 weeks prior to entry
6. High risk for CAD as defined by either documented CVD (including prior MI) or diabetes mellitus or 1 CVD risk factor (current smoking, hypertension, dyslipidemia, or hsCRP≥2mg/L.)
7. Individuals on stable doses of lipid lowering therapy and/or anti-hypertensive medication will be allowed in the study.
8. Appropriate documentation from medical records of prior receipt of pneumococcal vaccinations

Exclusion Criteria:

1. Women of childbearing potential or pregnant/nursing women
2. CABG surgery in the past 3 years
3. Class IV heart failure
4. Uncontrolled HTN
5. History of tuberculosis or latent TB that is not treated
6. Nephrotic syndrome or eGFR\< 30 ml/min/1.73m2
7. Active hepatic disease or active/chronic hepatitis B or C
8. Any prior malignancy including KS
9. Serious illness requiring hospitalization or active infection requiring antibiotics within 90 days
10. Requirement for live active vaccination 3 months prior to, during, and 3 months after study
11. Concurrent immune modulating therapy
12. Diabetes Mellitus
13. History of multiple imaging studies associated with radiation exposure
14. Neutropenia defined as ANC\<1500/mm
15. Triglycerides\>400 mg/dL
16. History of hypersensitivity to study drug
17. History of EBV-related lymphoproliferative disorders
18. Active or untreated latent TB infection

Primary outcomes:
measure: Change in CD4 Count From Baseline to Follow-up
timeFrame: weeks 4, 8, 12, 18, 24, and 36.
measure: Change in CD8 Count From Baseline to Follow-up
timeFrame: weeks 4, 8, 12, 18, 24, and 36.
measure: Change in Absolute Neutrophil Count From Baseline to Follow-up
timeFrame: weeks 4, 8, 12, 18, 24, and 36.
measure: Change in Platelet Count From Baseline to Follow-up
timeFrame: weeks 4, 8, 12, 18, 24, and 36.
measure: Change in Creatinine Count From Baseline to Follow-up
timeFrame: weeks 4, 8, 12, 18, 24, and 36.
measure: Change in AST From Baseline to Follow-up
timeFrame: weeks 4, 8, 12, 18, 24, and 36.
measure: Change in ALT From Baseline to Follow-up
timeFrame: weeks 4, 8, 12, 18, 24, and 36.
Secondary outcomes:
measure: Flow-Mediated Dilation (FMD)
timeFrame: Baseline and Week 12
measure: Arterial Inflammation Measured at Baseline and Follow-up at Week 12
timeFrame: Baseline (entry) and Week 12
measure: D-Dimer
timeFrame: Baseline, 4 weeks, 8 weeks, 12 weeks, and week 18
measure: Human Serum Amyloid A (SAA)
timeFrame: Baseline, 4 weeks, 12 weeks, and week 18
measure: Tumor Necrosis Factor Alpha (TNFa)
timeFrame: Baseline, 4 weeks, 12 weeks, and week 18
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Priscilla Hsue, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kentoffio K, Temu TM, Shakil SS, Zanni MV, Longenecker CT. Cardiovascular disease risk in women living with HIV. Curr Opin HIV AIDS. 2022 Sep 1;17(5):270-278. doi: 10.1097/COH.0000000000000756. Epub 2022 Jul 5.