Dipeptidyl Peptidase-4 Inhibition and Immune Function in HIV (DPPIVinHIV)
We will test the safety of a new class of anti-diabetes compounds (DPPIV-inhibitors) in people living with HIV. Future trials will examine efficacy for treating diabetes and reducing cardiovascular disease risk in people living with HIV.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
|Official Title:||A Blinded Randomized Controlled Pilot Immunologic and Virologic Safety Trial of an FDA-approved DPPIV-inhibitor in HIV+ Men and Women|
- CD4+ T-cell Count [ Time Frame: Monthly for 4 months ] [ Designated as safety issue: Yes ]
- Plasma HIV Viremia (Viral Load) [ Time Frame: Monthly for 6 months ] [ Designated as safety issue: Yes ]Percentage of participants with plasma HIV RNA copy number less than 48 copies/mL
- Soluble TNFR2; Serum Biomarkers of Immune Activation [ Time Frame: Baseline, week 8, week 16 ] [ Designated as safety issue: No ]serum soluble tumor necrosis factor receptor-2 concentration
- SDF1α; Serum Biomarkers of Immune Activation [ Time Frame: Baseline, week 8, week 16 ] [ Designated as safety issue: No ]serum stromal cell-derived factor-1α concentration
- RANTES; Serum Biomarkers of Immune Activation [ Time Frame: Baseline, week 8, week 16 ] [ Designated as safety issue: No ]serum Regulated on Activation, Normal T cell Expressed and Secreted concentration
- Oral Glucose Tolerance [ Time Frame: Baseline, week 8, week 16 ] [ Designated as safety issue: No ]Area under the 75-gr oral glucose tolerance curve (AUCg) based on plasma glucose values measured at 0, 30, 60, 90, and 120 mins post-glucose challenge.
- Self-reported Symptoms [ Time Frame: Monthly for 4 months ] [ Designated as safety issue: Yes ]Cumulative number of self-reported symptoms based on the Division of AIDS Grading Scale for the Severity of Adult Adverse Events (0-4 scale where 0 is no new symptoms, 4 is serious adverse event or toxicity)
|Study Start Date:||June 2010|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
Experimental: DPPIV inhibition
Four to six months of sitagliptin administration (100mg/d) to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status.
100 mg sitagliptin daily for 4-6 months
Placebo Comparator: Placebo
Four to six months of placebo to people living with HIV-1 who have well-controlled immunologic (CD4+ T-cell count >350 cells/µL) and virologic (plasma HIV RNA <50 copies/mL) status.
Daily placebo for 4-6 months
Human immunodeficiency virus (HIV)-infection and treatment with antiretroviral therapies are associated with several cardiometabolic risk factors; insulin resistance, diabetes, dyslipidemia, central adiposity, that increase risk for MI and stroke. A new class of drugs used to treat type 2 diabetes has been introduced; Dipeptidyl peptidase-IV (DPPIV)-inhibitors (Januvia®, Onglyza®, alogliptin). Dipeptidyl peptidase-IV (DPPIV)-inhibition could be a safe and effective therapy for HIV-associated insulin resistance and diabetes. However, no safety data exist. The research question is: If HIV+ adults with stable immunologic (CD4+ T-cell count >350 cells/μL) and virologic (plasma HIV RNA <50 copies/mL) function are given a DPPIV-inhibitor would their CD4+ T-cell count and plasma HIV RNA level increase, decrease, or stay the same? Theoretically, DPPIV-inhibition could enhance their immune system by increasing SDF-1α levels; a potent inhibitor of HIV-entry into T-cells, or harm the HIV+ immune system by inactivating CD26 on immune cells. We hypothesize that DPPIV-inhibition will not harm the immune system in HIV+ people. We propose a blinded randomized controlled pilot safety trial of an FDA-approved DPPIV-inhibitor in virologically- and immunologically-stable HIV+ men and women. We will monitor CD4+ T-cell count, plasma HIV RNA levels, immune activation markers, and safety outcomes (lipid/lipoprotein profiles, blood pressure, kidney and liver function) during 4-6 months of DPPIV-inhibitor exposure vs placebo in 20 HIV+ adults. If safety is confirmed, the efficacy of DPPIV-inhibition in HIV+ with insulin resistance will be tested in future trials that examine potential glucoregulatory and cardiovascular benefits.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01093651
|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|