Sitagliptin for Reducing Inflammation and Immune Activation

NCT ID: NCT02513771

Last Updated: 2018-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2017-01-10

Brief Summary

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 evaluated 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.

Detailed Description

ACTG A5346 is a phase II, randomized, double-blinded, placebo-controlled, trial of sitagliptin 100 mg vs. placebo for 16 weeks followed by a 4-week post-intervention follow-up. A5346 studied whether sitagliptin reduced plasma concentrations of sCD14 in HIV-infected men and women ≥18 years of age who were on suppressive ART with HIV-1 RNA below the limit of quantification at screening and for at least the prior 48 weeks. Participants were randomized 1:1 to Sitagliptin arm vs. Placebo arm, and were stratified by screening CD4 count (100-350 vs. >350 cells/mm^3) and statin use (on statins vs. not on statins).

Conditions

HIV-1 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sitagliptin Arm

Sitagliptin (Januvia) 100 mg one tablet daily p.o. for 16 weeks, followed by a 4-week post-treatment follow-up.

Group Type: ACTIVE_COMPARATOR

Sitagliptin

Intervention Type: DRUG

100 mg one tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up

Placebo Arm

Placebo for sitagliptin one tablet daily p.o.for 16 weeks, followed by a 4-week post-treatment follow-up.

Group Type: PLACEBO_COMPARATOR

Placebo for sitagliptin

Intervention Type: DRUG

One tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up.

Interventions

Sitagliptin

100 mg one tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up

Intervention Type: DRUG

Placebo for sitagliptin

One tablet taken orally daily for 16 weeks, followed by a 4-week post-treatment follow-up.

Intervention Type: DRUG

Other Intervention Names

Januvia; Placebo

Eligibility 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/mm^3 obtained within 90 days prior to study entry.
• The following laboratory values obtained within 90 days prior to entry.

• Absolute neutrophil count (ANC) ≥750/mm^3
• Hemoglobin ≥8.0 g/dL
• Platelet count ≥50,000/mm^3
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Dube, MD

Role: STUDY_CHAIR

University of Southern California

Kevin Yarasheski, PhD

Role: STUDY_CHAIR

Washington University School of Medicine

Locations

University of Southern California (1201)

Los Angeles, California, United States

UCLA CARE Center CRS (601)

Los Angeles, California, United States

Harbor-UCLA Med. Ctr. CRS (603)

Torrance, California, United States

Whitman Walker Health CRS (31791)

Washington D.C., District of Columbia, United States

Washington University CRS (2101)

St Louis, Missouri, United States

Cornell CRS (7804)

New York, New York, United States

Columbia Physicians and Surgeons CRS (30329)

New York, New York, United States

University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

Rochester, New York, United States

Unc Aids Crs (3201)

Chapel Hill, North Carolina, United States

Greensboro CRS (3203)

Greensboro, North Carolina, United States

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, United States

Case CRS (2501)

Cleveland, Ohio, United States

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, United States

Hosp. of the Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, United States

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, United States

Houston AIDS Research Team CRS (31473)

Houston, Texas, United States

Countries

United States

Other Identifiers

UM1AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5346

Identifier Type: -

Identifier Source: org_study_id