Effectiveness of Sitagliptin for HIV Insulin Resistance and Inflammation

NCT01552694 | Completed Phase 3 Results

• 1 other identifier: 41052
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Inflammation; Macrophage Infiltration; Cardiovascular Disease

Keywords

cardiometabolic complications

Outcome Measures

Primary Outcomes (3)

• Inflammatory Biomarker 1: Plasma hsCRP Concentration

  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.

  2 months

• Inflammatory Biomarker 2: Plasma IL-6 Concentration

  There are 3 levels of the primary outcome measure; hsCRP, IL-6, and D-dimer concentrations measured at baseline and week 8

  2 months

• Inflammatory Biomarker 3: Serum D-dimer Concentration

  There are 3 levels of the primary outcome measure, hsCRP, IL-6, and D-dimer

  2 months

Secondary Outcomes (2)

• Fold Change in Adipose Inflammation Marker CCL2 (MCP-1) mRNA Expression

  Baseline to 2 months

• Percent Change in Blood Endothelial Progenitor Cells

  Baseline to 2 months

Study Arms (2)

Sitagliptin

EXPERIMENTAL

100 mg sitagliptin/day for 2 months

Drug: Sitagliptin

Placebo

PLACEBO COMPARATOR

Matching placebo daily for 2 months

Drug: Placebo

Interventions

Sitagliptin DRUG

Oral, 100 mg/day for 2 months

Also known as: Januvia

Sitagliptin

Placebo DRUG

oral, matching placebo daily for 2 months

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Best C, Struthers H, Laciny E, Royal M, Reeds DN, Yarasheski KE. Sitagliptin Reduces Inflammation and Chronic Immune Cell Activation in HIV+ Adults With Impaired Glucose Tolerance. J Clin Endocrinol Metab. 2015 Jul;100(7):2621-9. doi: 10.1210/jc.2015-1531. Epub 2015 May 4.

  PMID: 25938633 RESULT

Related Links

• Center for Clinical Studies- Washington University

MeSH Terms

Conditions

Inflammation; Cardiovascular Diseases

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: Kevin Yarasheski, PhD
• Organization: Washington University School of Medicine

key@wustl.edu

3143628173

Study Officials

• Kevin E Yarasheski, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: March 8, 2012
• First Posted: March 13, 2012
• Study Start: October 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 8, 2018
• Results First Posted: March 5, 2015

Record last verified: 2018-03

Locations

US (1)