Effects of Sitagliptin in Individuals With Genetically Decreased DPP4

Heart Failure Clinical Trial

Official title:

Effects of Sitagliptin in Individuals With Genetically Decreased DPP4

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04323189
• Other study ID #: 834482
• Status: Recruiting
• Phase: Phase 4
• Start date: August 26, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2023
• Source: University of Pennsylvania
• Contact: Jessica R Wilson, MD, MS
• Phone: (215) 898-3389
• Email: jessica.wilson3[@]uphs.upenn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 and 10 controls. Among these, there will be five heterozygous cases and five matched controls with elevated blood pressure (history of blood pressure 130/80 on more than one occasion or prior diagnosis of hypertension by a medical provider) and five cases and five controls without hypertension.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Genetics Disease
• Heart Failure
• Type2 Diabetes

Intervention

Drug:
• Sitagliptin 100mg
Sitagliptin will be administered daily for 7 days, with a study day on day 7.
• Placebo Oral Tablet
Placebo will be administered daily for 7 days, with a study day on day 7.

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dipeptidyl peptidase 4 (DPP4)	DPP4 activity and antigen concentration	during study days 1 and 2
Secondary	Glucose Area Under the Curve	Glucose will be measured before after the mixed meal during sitagliptin and placebo. Area under the curve will be calculated based on at least 10 time points after the meal.	Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Secondary	Intact DPP4 substrates with cardiovascular properties (other than GLP-1)	Cardiovascular biomarkers include: CXCL12, substance P, neuropeptide Y, and brain natriuretic peptide. These are peptides that are also DPP4 substrates and are rapidly inactivated by this peptidase.	Before the meal (t=-15 or -1 min) on study days 1 and 2
Secondary	Disposition index	Disposition index will be calculated from insulin sensitivity and insulin secretion. These variables will be computed using mathematical modeling of insulin and c-peptide. We will collect insulin and c-peptide at least 10 time points after the meal.	Calculated from samples collected before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Secondary	Mean blood pressure	Measured via an automated blood pressure cuff approximately every 15 minutes	Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Secondary	Glucagon-like peptide-1 (GLP-1)	This is released in response to a meal and rapidly degraded by DPP4. We will collect samples for at least six time points after the meal.	Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Secondary	CD26	CD26 is DPP4 on T cells and monocytes.	Before the meal or at baseline (t=-15 or -1 min) on study days 1 and 2
Secondary	Surrogate markers of lipolysis	Triglycerides, free fatty acids; We will collect samples at least six time points after the meal.	Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Secondary	Mean heart rate	Measured via an automated blood pressure cuff approximately every 15 minutes	Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2