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Sitagliptin for Reducing Inflammation and Immune Activation

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02513771
First Posted: August 3, 2015
Last Update Posted: November 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group
  Purpose
The purpose of the study is to evaluate whether sitagliptin (Januvia is the brand name for sitagliptin) reduces inflammation and immune activation markers in HIV-infected men and women when compared to a placebo (inactive medication like a dummy pill). The study will evaluate whether taking 100 mg of sitagliptin by mouth daily for 16 weeks is safe and effective for HIV-infected persons on antiretroviral therapy (ART) who do not have diabetes. Sitagliptin is a medication that is used to treat people with diabetes (high blood sugar) but also may reduce inflammation in the body.

Condition Intervention Phase
HIV-1 Infection Drug: Sitagliptin Drug: Placebo for sitagliptin Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blinded, Placebo-Controlled Trial of a Dipeptidyl Peptidase-4 Inhibitor (Sitagliptin, Januvia) for Reducing Inflammation and Immune Activation in HIV-Infected Men and Women: A Multicenter Trial of the AIDS Clinical Trials Group (ACTG)

Resource links provided by NLM:


Further study details as provided by AIDS Clinical Trials Group:

Primary Outcome Measures:
  • Change in sCD14 from baseline to Week 16 [ Time Frame: Pre-entry, Week 0, Week 15, Week 16 ]

Secondary Outcome Measures:
  • Change from baseline to week 16 in circulating levels of inflammatory biomarkers [ Time Frame: Week 0, Week 16 ]
    inflammatory biomarkers include CXCL10 (IP-10), sCD163, IL-6, sTNFR1 & 2, hs-CRP, and sCD26

  • Change from baseline to week 16 in the percentage and number of CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ T-cell subpopulations [ Time Frame: Week 0, Week 16 ]
  • Change from baseline to week 16 in the percentages and number of CD14+CD16-CD14+CD16+ and CD14dim CD16++ monocyte subpopulations. [ Time Frame: Week 0, Week 16 ]
  • Change from baseline to week 16 in CD4+/CD8+ T-cell ratio [ Time Frame: Week 0, Week 16 ]
  • Occurrence of Grade ≥3 AEs and selected Grade ≥2 AEs related to study drug [ Time Frame: Week 0 to Week 20 ]
    The DAIDS Adverse Event Grading Table, Version 2.0, will be used for grading of AEs

  • Change from week 16 to week 20 for plasma sCD14 levels [ Time Frame: Week 16, Week 20 ]
    plasma biomarkers include CXCL10 (IP-10), sCD163, IL-6, sTNFR1 & 2, hs-CRP, and sCD26

  • Change from week 16 to week 20 for plasma biomarker levels percentage and number of T-cell and monocyte subpopulations [ Time Frame: Week 16, Week 20 ]
    monocyte subpopulations include CD14+CD16-, CD14+CD16+, and CD14dim CD16+

  • Change from week 16 to week 20 for CD4+/CD8+ T-cell ratio [ Time Frame: Week 16, Week 20 ]

Enrollment: 90
Study Start Date: September 2015
Study Completion Date: January 10, 2017
Primary Completion Date: December 13, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1: Sitagliptin (Januvia) Drug: Sitagliptin
100 mg one tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up
Other Name: Januvia
Placebo Comparator: Arm 2: Placebo for sitagliptin Drug: Placebo for sitagliptin
One tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented HIV-1 infection.
  • Currently on an antiretroviral regimen consisting of at least 2 NRTIs and either a protease inhibitor boosted with low dose ritonavir, an integrase inhibitor, or an NNRTI. (Other ART regimens may be acceptable. Sites must consult the protocol team for approval)
  • Currently on continuous ART for ≥48 weeks prior to study entry with no interruption longer than 7 consecutive days during that period.
  • Plasma HIV-1 RNA levels below 75 copies/mL for at least 48 weeks prior to study entry. The participant must have a minimum of two values in the last 48 weeks obtained >30 days apart, with the most recent value obtained within 90 days prior to entry. (Single determinations that are between the assay quantification limit and 500 copies/mL (i.e., "blips") are allowed as long as the preceding and subsequent determinations are below the level of quantification).
  • CD4+ cell count ≥100 cells/mm3 obtained within 90 days prior to study entry.
  • The following laboratory values obtained within 90 days prior to entry.

    • Absolute neutrophil count (ANC) ≥750/mm3
    • Hemoglobin ≥8.0 g/dL
    • Platelet count ≥50,000/mm3
    • Calculated creatinine clearance (CrCl) ≥60 mL/min as estimated by the Cockroft-Gault formula NOTE: Calculation for the Cockcroft-Gault equation is available at https://www.fstrf.org/apps/cfmx/apps/common/Portal/index.cfm
    • Aspartate aminotransferase (AST) (SGOT) ≤5 x upper limit of normal (ULN).
    • alanine aminotransferase (ALT) (SGPT) ≤5 x ULN.
    • alkaline phosphatase ≤5 x ULN.
    • Total bilirubin ≤2.5 x ULN (if the participant is receiving atazanavir, a total bilirubin of ≤5 x ULN is acceptable).
    • Hemoglobin A1C ≤6.5%
  • For females of reproductive potential, adequate contraception.
  • Karnofsky performance score >/=70 within 90 days prior to entry.
  • Ability and willingness of participant or legal guardian/representative to provide informed consent.
  • Participants on statin therapy must be stable on the same dose for at least the prior 12 weeks with no anticipated change in statin or dose during the intervention.

Exclusion Criteria:

  • Change in the ART regimen within the 12 weeks prior to study entry, or anticipated/intended modification of ART during the study period.
  • Two or more HIV-1 RNA determinations >200 copies/mL within the 48 week period prior to study entry.
  • History of clinical pancreatitis or diabetes mellitus diagnosed by a medical provider.
  • Acute or chronic liver disease with evidence of cirrhosis or portal hypertension.
  • Chronic hepatitis C (defined as HCV antibody positive and HCV RNA detectable).
  • History of chronic hepatitis B (defined as surface antibody negative, surface antigen positive, and/or HBV DNA detectable).
  • Use of any immunomodulator, HIV vaccine, investigational therapy, or anti-TNF therapies within 90 days prior to study entry.
  • Active malignancy with expected need for systemic chemotherapy or radiation therapy during the study period.
  • Use of human growth hormone, tesamorelin, testosterone or anabolic steroids within 90 days prior to study entry (except chronic, stable, replacement dosages in men with diagnosed hypogonadism is allowed).
  • Pregnant or breastfeeding.
  • Use of any anti-diabetic medication or GLP-1 analogues within the 12 weeks prior to study entry.
  • Current diagnosis of congestive heart failure.
  • Known allergy/sensitivity or any hypersensitivity to components of the study drug or its formulation.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Acute or serious illness requiring systemic treatment and/or hospitalization within 90 days prior to entry.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02513771


Locations
United States, California
University of Southern California (1201)
Los Angeles, California, United States, 90033-1079
UCLA CARE Center CRS (601)
Los Angeles, California, United States, 90095
Harbor-UCLA Med. Ctr. CRS (603)
Torrance, California, United States, 90502
United States, District of Columbia
Whitman Walker Health CRS (31791)
Washington, D.C., District of Columbia, United States, 20009
United States, Missouri
Washington University CRS (2101)
Saint Louis, Missouri, United States, 63110
United States, New York
Cornell CRS (7804)
New York, New York, United States, 10011
Columbia Physicians and Surgeons CRS (30329)
New York, New York, United States, 10032
University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs (3201)
Chapel Hill, North Carolina, United States, 27516
Greensboro CRS (3203)
Greensboro, North Carolina, United States, 27401
United States, Ohio
Univ. of Cincinnati CRS (2401)
Cincinnati, Ohio, United States, 45267
Case CRS (2501)
Cleveland, Ohio, United States, 44106
The Ohio State Univ. AIDS CRS (2301)
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS (6201)
Philadelphia, Pennsylvania, United States, 19104
Pittsburgh CRS (1001)
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Houston AIDS Research Team CRS (31473)
Houston, Texas, United States, 77030
Sponsors and Collaborators
AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: Michael Dube, MD University of Southern California
Study Chair: Kevin Yarasheski, PhD Washington University School of Medicine
  More Information

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT02513771     History of Changes
Other Study ID Numbers: ACTG A5346
UM1AI068636 ( U.S. NIH Grant/Contract )
First Submitted: July 13, 2015
First Posted: August 3, 2015
Last Update Posted: November 7, 2017
Last Verified: May 2017

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Sitagliptin Phosphate
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action