Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Sitagliptin and HIV

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Washington University School of Medicine
Information provided by (Responsible Party):
Kevin Yarasheski, PhD, Washington University School of Medicine Identifier:
First received: March 8, 2012
Last updated: January 22, 2014
Last verified: January 2014

March 8, 2012
January 22, 2014
October 2012
October 2014   (final data collection date for primary outcome measure)
inflammatory biomarkers [ Time Frame: 2 months ] [ Designated as safety issue: No ]
Fasting serum and plasma samples obtained at baseline, week 4 and 8 are batched for ELISA analysis (end of sudy) of hsCRP, IL-6 and D-dimer concentrations.
Same as current
Complete list of historical versions of study NCT01552694 on Archive Site
  • 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.
Same as current
Not Provided
Not Provided
Sitagliptin and HIV
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.

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.

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.

Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Inflammation
  • Macrophage Infiltration
  • Cardiovascular Disease
  • Drug: Sitagliptin
    Oral, 100 mg/day for 2 months
    Other Name: Januvia
  • Drug: Placebo
    oral, matching placebo daily for 2 months
  • Experimental: Sitagliptin
    100 mg sitagliptin/day for 2 months
    Intervention: Drug: Sitagliptin
  • Placebo Comparator: Placebo
    Matching placebo daily for 2 months
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
January 2015
October 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 18-65 yr old HIV infected men and women.
  • Stable (at least the past 6 months) on combined antiretroviral therapy (cART).
  • Stable immune (> 300 CD4+ T-cells/µL) and virologic (< 50 copies HIV RNA/mL) status.
  • Insulin resistant/impaired glucose tolerance (fasting glucose 100-125mg/dL, or 2-hr glucose 140-200mg/dL or fasting HOMA-IR= 2.5-6.0).
  • Waist circumference > 102 cm (men), > 88 cm (women).
  • BMI > 20 kg/m2.
  • Fasting hypertriglyceridemia > 150 mg/dL.
  • Low HDL-cholesterol (< 40 mg/dL in men or < 50 mg/dL in women).
  • Platelet count > 30,000/mm3.
  • Absolute neutrophil count > 750/mm3.
  • Transaminases < 2.5x the upper limit of normal.
  • Long-term non-progressors (not taking anti-HIV medications) are not eligible.

Exclusion Criteria:

  • Diabetes (T2DM, IDDM or diabetic ketoacidosis) or taking any glucose-lowering medication (e.g., insulin, TZDs, metformin, sulfonylurea).
  • Any agent that might artifactually alter glycemic control (e.g., glucocorticoids, megace, rhGH, GH-secretagogue, testosterone derivatives, creatine monohydrate, chromium picolinate, AA/protein supplements, medium- or long-chain fatty acids) during 6 months prior to or during enrollment.
  • History of serious CV disease. NYHA Functional Class III or IV (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, stroke, resting hypertension > 160/95 mmHg), irregular heart rhythm, resting ST-segment depression > 1mm). Treatment with medications for CV condition (e.g., α- or ß-blockers). Some BP-lowering medications (Ca++channel blocker, diuretic, or ACE inhibitor) are permitted.
  • Moderate to severe renal insufficiency. Serum creatinine > 1.7 mg/dL (men) > 1.5 mg/dL (women).
  • Plan or anticipate a change in anti-HIV medications during the study.
  • Lipid-lowering medications are permitted (fibrate or statin or niacin), but must be stable on that agent for at least 6 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period.
  • Chronic hepatitis B (HBV-surface antigen positive). Active hepatitis C (detectable Hep C RNA).
  • Positive urine drug test for opiates, methamphetamine, heroin, cocaine. Active substance abuse that the MD-scientist believes may compromise safety, compliance, interfere with study drug or data interpretation.
  • Hematocrit < 34% in men or < 25% in women with symptoms (fatigue, "tired-legs", shortness of breath). Hemoglobin < 10 gm/dL with symptoms.
  • Pregnant or nursing mothers. Women must agree to use an acceptable form of birth control during the study. If using birth control pills-must be stable on this medication for at least 6 months prior to enrollment.
  • Active malignancy or treatment with chemotherapeutic agents or radiation therapy or any cytokine or anti-cytokine therapy during 6 months prior to enrollment.
  • History of pancreatitis
  • > 10% unintentional weight loss during the 6 months prior to enrollment.
  • Reduced cognitive function/unable to provide voluntary informed consent. Prisoners are excluded.
  • Blinded investigational drugs for 3 months prior to enrollment that will not be unblinded before enrollment.
  • Nausea, vomiting, diarrhea (> 4 loose stools/day) that are unresponsive to treatment.
18 Years to 65 Years
Contact: Kevin E Yarasheski, PhD 3143628173
Contact: Erin Laciny, MSEd 3147475371
United States
41052, 41052
Kevin Yarasheski, PhD, Washington University School of Medicine
Washington University School of Medicine
Not Provided
Principal Investigator: Kevin E Yarasheski, PhD Washington University School of Medicine
Washington University School of Medicine
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP