Effectiveness of Sitagliptin for HIV Insulin Resistance and Inflammation
Condition: Inflammation; Macrophage Infiltration; Cardiovascular Disease
MeSH terms: Cardiovascular Diseases; Insulin Resistance; Inflammation
Intervention: Sitagliptin; Placebo
Intervention description: Oral, 100 mg/day for 2 months; oral, matching placebo daily for 2 months
Intervention MeSH terms: Sitagliptin Phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: cardiometabolic complications

Summary:

      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.
    

Eligibility criteria:

        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.