Effects of Sitagliptin in Individuals With Genetically Decreased DPP4

University of Pennsylvania

Status and phase: Active, not recruiting; Phase 4

Conditions: Genetics Disease; Type2 Diabetes; Heart Failure

Treatments: Drug: Placebo Oral Tablet; Drug: Sitagliptin 100mg

Study type: Interventional

Funder types: Other

Identifiers

NCT04323189

834482

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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20 participants in 2 patient groups

Crossover AB

Other group

Description:

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.

Treatment:

Drug: Sitagliptin 100mg

Drug: Placebo Oral Tablet

Crossover BA

Other group

Description:

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.

Treatment:

Drug: Sitagliptin 100mg

Drug: Placebo Oral Tablet