Effects of Sitagliptin in Individuals With Genetically Decreased DPP4

NCT04323189 | Active Not Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 834482
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Genetics Disease; Type2 Diabetes; Heart Failure

Keywords

genetics; sitagliptin; DPP4 inhibition; heart failure; type 2 diabetes

Outcome Measures

Primary Outcomes (1)

• Dipeptidyl peptidase 4 (DPP4)

  DPP4 activity and antigen concentration

  during study days 1 and 2

Secondary Outcomes (7)

• Glucose Area Under the Curve

  Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2

• Disposition index

  Calculated from samples collected before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2

• Mean blood pressure

  Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2

• Glucagon-like peptide-1 (GLP-1)

  Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2

• CD26

  Before the meal or at baseline (t=-15 or -1 min) on study days 1 and 2

Study Arms (2)

Crossover AB

OTHER

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.

Drug: Sitagliptin 100mg; Drug: Placebo Oral Tablet

Crossover BA

OTHER

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.

Drug: Sitagliptin 100mg; Drug: Placebo Oral Tablet

Interventions

Sitagliptin 100mg DRUG

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

Also known as: Januvia

Crossover AB; Crossover BA

Placebo Oral Tablet DRUG

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

Crossover AB; Crossover BA

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Genetic Diseases, Inborn; Heart Failure; Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Diseases; Cardiovascular Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Jessica R Wilson, MD, MS

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Neither subjects, nor the investigator or key study personnel will know drug randomization until after data analyses are completed.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor in Medicine, Division of Endocrinology, Diabetes, and Metabolism

Model Details: blinded 2:2 crossover, placebo-controlled

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: March 26, 2020
• Study Start: August 26, 2020
• Primary Completion: February 27, 2025
• Study Completion: February 28, 2026
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Deidentified data will become available upon completion of the pilot study

Locations

US (1)