Sitagliptin and HIV
People living with human immunodeficiency virus infection (HIV) have 2-4fold greater risk for developing diabetes and heart disease than the general population. They need safe and effective treatments that reduce the risk for developing diabetes and heart disease, and improve their quality of life. This project will explore whether a new anti-diabetes medication (Januvia) with a novel mechanism of action reduces inflammation, and improves blood vessel function in HIV infected men and women with several risk factors for developing cardiovascular disease.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||A Double Blind, Randomized, Placebo Controlled Study to Determine the Physiological Effectiveness of Januvia (100 mg/d) for Reducing Inflammation and Increasing Endothelial Progenitor Cell Number in Human Immunodeficiency Virus (HIV) Infected Men and Women With Insulin Resistance and Central Adiposity.|
- Inflammatory Biomarker 1: Plasma hsCRP Concentration [ Time Frame: 2 months ] [ Designated as safety issue: No ]Fasting serum and plasma samples obtained at baseline and week 8 are batched for ELISA analysis (end of sudy) of hsCRP, IL-6 and D-dimer concentrations.
- Inflammatory Biomarker 2: Plasma IL-6 Concentration [ Time Frame: 2 months ] [ Designated as safety issue: No ]There are 3 levels of the primary outcome measure; hsCRP, IL-6, and D-dimer concentrations measured at baseline and week 8
- Inflammatory Biomarker 3: Serum D-dimer Concentration [ Time Frame: 2 months ] [ Designated as safety issue: No ]There are 3 levels of the primary outcome measure, hsCRP, IL-6, and D-dimer
- Adipose Inflammation [ Time Frame: 2 months ] [ Designated as safety issue: No ]Adipose tissue from obese, insulin resistant subjects is characterized by increased macrophage infiltration and overexpression of inflammatory cytokines/chemokines. In obese humans, the presence of CD68+ macrophages in direct contact with mature adipocytes has been noted in histologic sections of adipose tissue, and these appear as a macrophage "crown" around individual adipocytes. In adipocyte sections, we will use positive immunohistochemical staining for CD68 to quantify the density of macrophages and the frequency of "crown' like structures.
- Blood Endothelial Progenitor Cells [ Time Frame: 2 months ] [ Designated as safety issue: No ]Monocytes are isolated from 20 mL blood. CD34+/VEGFR2+ and CD133+/CD34+/VEGFR2+ monocytes are counted (flow cytometry) and represent markers for endothelial progenitor cell number.
|Study Start Date:||October 2012|
|Study Completion Date:||December 2014|
|Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
100 mg sitagliptin/day for 2 months
Oral, 100 mg/day for 2 months
Other Name: Januvia
Placebo Comparator: Placebo
Matching placebo daily for 2 months
oral, matching placebo daily for 2 months
People living with human immunodeficiency virus (HIV+) infection have a 2-fold greater prevalence and incidence of T2DM and cardiovascular disease (CVD) than the general population. The investigators lack safe and effective treatments for these HIV related cardiometabolic complications despite the fact that HIV infected adults represent an ideal clinical population in which to study interactions among chronic low-grade pro-inflammatory processes that are linked to the development of adipose accumulation, insulin resistance, ß-cell secretory failure, vascular endothelial dysfunction, atherosclerosis and CVD. Dipeptidyl peptidase-IV (DPP4)-inhibitors represent a new drug class that safely and effectively regulate glycemia in T2DM, but have not been adequately tested in HIV. Of note, pre-clinical studies suggest that DPP4-inhibitors have several pleiotropic actions that may specifically benefit people living with HIV infection. For example, DPP4 inhibition reduced adipose macrophage infiltration & inflammation and increased the number of bone-derived endothelial progenitor cells in the circulation. Our preliminary findings indicate that DPP4 inhibition is virologically and immunologically safe in non-diabetic HIV+ adults taking combination antiretroviral therapy (in preparation), but the potential pleiotropic benefits have not been examined in HIV. The investigators propose a randomized, double blind, placebo controlled physiological study to test 2 potential pleiotropic benefits of DPP4 inhibition (100 mg sitagliptin/d, 8 wk): reduce circulating and adipose-specific markers of inflammation; and increase endothelial progenitor cell numbers used for vascular repair in 36 HIV+ adults with insulin resistance, central adiposity and CVD risk factors. The investigators hypothesize that sitagliptin will reduce circulating cytokine levels, reduce adipose tissue macrophage number and inflammation, and increase the number of circulating endothelial progenitor cells in HIV infected men and women. These physiological studies will advance our understanding about the efficacy of DPP4 inhibition in this high-risk group, and may help prevent the inexorable transition from insulin resistance to T2DM and CVD in HIV infected men and women.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01552694
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Kevin E Yarasheski, PhD||Washington University School of Medicine|