Effects of Sitagliptin in Individuals With Genetically Decreased DPP4

NCT ID: NCT04323189

Last Updated: 2026-01-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-26
• Study Completion Date: 2026-02-28

Brief Summary

This is a pilot clinical trial to test the hypothesis that during sitagliptin (DPP4 inhibitor), individuals heterozygous for DPP4 loss of function variants will have a reduction in DPP4 activity and antigen, lower glucose after a mixed meal, and higher levels of intact DPP4 substrates compared to during placebo and compared to matched controls.

Detailed Description

Participants of this pilot clinical trial will be randomized in a blinded 2:2 crossover manner to receive placebo and sitagliptin 100 mg/d (DPP4 inhibitor), in random order. Subjects will receive each intervention for seven days, with a study day on day 7. Each intervention will be separated by a 4-week washout period. Each subject will have up to four separate visits: 1) DXA, echocardiogram, 2) cardiac MRI, 3) mixed meal during placebo, 4) mixed meal during sitagliptin.

The study will include 10 cases (heterozygous for DPP4 loss of function variant) and 10 controls.

Conditions

Genetics Disease; Type2 Diabetes; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Crossover AB

Subjects in arm A will first receive placebo daily for 7 days in the first intervention followed by sitagliptin 100mg/d for 7 days in the crossover intervention.

Group Type: OTHER

Sitagliptin 100mg

Intervention Type: DRUG

Sitagliptin will be administered daily for 7 days, with a study day on day 7.

Placebo Oral Tablet

Intervention Type: DRUG

Placebo will be administered daily for 7 days, with a study day on day 7.

Crossover BA

Subjects in arm B will first receive sitagliptin 100mg/d for 7 days in the first intervention followed by placebo for 7 days in the crossover intervention.

Group Type: OTHER

Sitagliptin 100mg

Intervention Type: DRUG

Sitagliptin will be administered daily for 7 days, with a study day on day 7.

Placebo Oral Tablet

Intervention Type: DRUG

Placebo will be administered daily for 7 days, with a study day on day 7.

Interventions

Sitagliptin 100mg

Sitagliptin will be administered daily for 7 days, with a study day on day 7.

Intervention Type: DRUG

Placebo Oral Tablet

Placebo will be administered daily for 7 days, with a study day on day 7.

Intervention Type: DRUG

Other Intervention Names

Januvia

Eligibility Criteria

Inclusion Criteria

• Participant of the Penn Medicine Biobank who is willing to be recontacted to participate in future research.
• Cases are defined as adults 18-70 years with likely decreased DPP4.
• Controls are defined as adults who are matched to cases by: age, gender, race, BMI, hypertension status, diabetes status, renal function, and medication use that may affect outcomes of interest.

Exclusion Criteria

• The study will exclude volunteers with any significant medical conditions that may interfere with study participation, data interpretation, or pose safety risk(s) to the subject.
• Recent hospitalization or acute illness such as infection within the past two weeks
• Pregnancy
• Use of insulin
• Use of a GLP-1 agonist or DPP4 inhibitor medication
• Use of oral diabetes agents other than metformin unless matched with controls
• Type 1 diabetes
• Chronic steroid use or use within the last 30 days
• Significant liver disease including liver enzymes >3 x upper limit of normal range
• Renal dysfunction defined as eGFR< 50mL/min/1.73m2
• Significant cardiac disease such as heart transplantation
• Significant gastrointestinal conditions that may interfere with drug absorption or GLP-1 release including bariatric surgery
• Significant hematologic disease such as hematocrit <35%
• Use of chronic anticoagulation
• Severe pulmonary disease
• Severe neurologic or psychiatric disease
• Inability to comprehend study procedures

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Jessica R.Wilson, MD, MS

Instructor in Medicine, Division of Endocrinology, Diabetes, and Metabolism

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jessica R Wilson, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

834482

Identifier Type: -

Identifier Source: org_study_id