Chronic Inflammation, HIV, Obesity and Overweight
Conditions
Brief summary
This is a prospective cohort study of 12 overweight (with one or more weight-related condition) or obese adults with well controlled HIV-1 on antiretroviral therapy (ART). An initial dose of tirzepatide (TZP) 2.5 mg subcutaneous (SQ) once weekly will be given, escalated by 2.5 mg at 4-week intervals to a final dose of 7.5mg. The investigators will collect the following information via review of the medical record: age, race/ethnicity, sex, medical conditions, medications, most recent standard of care HIV labs (including T-cell panel and HIV-1 viral load). The primary outcome will be the change in baseline body weight at 12 weeks. Secondary outcomes will be changes in body composition, liver fat content and liver stiffness, inflammatory markers, cardiometabolic markers (lipids and HbA1c), and monocytes at 12 weeks. There will be a 4-week safety follow up off TZP.
Interventions
DRUGTirzepatide
Tirzepatide is approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes, obesity and overweight with at least one weight-related medical condition, and moderate to severe obstructive sleep apnea. An initial dose of TZP 2.5 mg subcutaneous (SQ) once weekly will be given, escalated by 2.5 mg at 4-week intervals to a final dose of 7.5mg.
Sponsors
University of Hawaii
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Age ≥ 18 years HIV-1 infection (well controlled) * Documented HIV-1 infection ≥ 1 year prior to study entry (ELISA confirmed by Western blot or HIV-1 RNA) AND * HIV-1 RNA \<200 copies/mL for ≥ 6 months Stable ART · Receiving a stable antiretroviral regimen for at least 1 year prior to study entry Overweight * BMI ≥27 kg/m2 plus at least one weight-related condition (defined as a medical history of dyslipidemia, hypertension, cardiovascular disease, or obstructive sleep apnea) OR Obese * BMI ≥ 30 kg/m2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Baseline Body Weight | 12 weeks | The primary outcome will be the change in baseline body weight (measured in lbs) at 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inflammatory Markers: GM-CSF | 12 weeks | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: GM-CSF. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. |
| Change in cardiometabolic markers | 12 weeks | We will evaluate HbA1c and a lipid profile at the baseline, week 12 and week 16 study visits. |
| Monocyte Subset Analysis | Week 12 and week 16 | Monocyte subsets will be phenotyped from thawed/washed banked cryopreserved PBMCs (from blood drawn at baseline, week 12, and week 16) using a multiparametric panel of conjugated monoclonal antibodies: CD3, CD14, CD16, CD56, CD19, CD20, HLA-DR antibodies with Live/Dead fixable yellow dead cell stain (YARD). Data will be acquired on a 4-laser BD LSRFortessa Flow Cytometer with all compensation and gating analyses performed with the FlowJo analytical software to determine levels of classical (CD14 ++ CD16 -), intermediate (CD14 ++ CD16 +), non-classical (CD14 + CD16 ++), and transitional (CD14 + CD16 -) monocytes. |
| Change in Inflammatory Markers: IFN-γ | 12 weeks | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IFN-γ. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. |
| Change in Inflammatory Markers: IL-1β | 12 weeks | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IL-1β. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. |
| Change in Inflammatory Markers: IL-2 | 12 weeks | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IL-2. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. |
| Change in Inflammatory Markers: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 | 12 weeks | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. |
| Change in Inflammatory Markers: TNF-α | 12 weeks | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: TNF-α. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. |
| Change in Inflammatory Markers: NFkB | 12 weeks | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: NFkB. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. |
| Change in Inflammatory Markers: sCD163, and sCD14 | 12 weeks | All biomarkers will be assayed from banked plasma using a Luminex multiplex assay and ELISAs performed per manufacturer's instructions. A Cytokine 10-Plex Human Panel (ThermoFisher Scientific) with data acquired using Luminex 200TM system (Luminex) and ELISAs (ThermoFisher Scientific) with data acquired using a Victor X3 plate reader (PerkinElmer) will be utilized to measure the following inflammatory biomarkers: sCD163, and sCD14. Cytokine standards supplied by the manufacturer will be run in duplicate on each plate. |
| Body composition | 12 weeks | Body composition (total, peripheral and truncal fat, and lean tissue) by dual energy absorptiometry (DEXA) |
| Waist circumference | 12 weeks | Changes in waist circumference over 12 weeks of therapy |
| Liver fat content | 12 weeks | Changes in Liver fat content (Controlled Attenuation Parameter, CAP) over 12 weeks |
| Liver stiffness measurement (LSM) | 12 weeks | Changes in Liver stiffness measurement (LSM) over 12 weeks |
Countries
United States
Outcome results
None listed