Clinical trial NCT04323189: Effects of Sitagliptin in Individuals With Genetically Decreased DPP4
Official title: Effects of Sitagliptin in Individuals With Genetically Decreased DPP4
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Genetics Disease
Type2 Diabetes
Heart Failure
Keywords: genetics
sitagliptin
DPP4 inhibition
heart failure
type 2 diabetes
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2020-03-26
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: blinded 2:2 crossover, placebo-controlled
Primary purpose: OTHER

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 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.

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

Primary outcomes:
measure: Dipeptidyl peptidase 4 (DPP4)
timeFrame: during study days 1 and 2
Secondary outcomes:
measure: Glucose Area Under the Curve
timeFrame: Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
measure: Intact DPP4 substrates with cardiovascular properties (other than GLP-1)
timeFrame: Before the meal (t=-15 or -1 min) on study days 1 and 2
measure: Disposition index
timeFrame: Calculated from samples collected before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
measure: Mean blood pressure
timeFrame: Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
measure: Glucagon-like peptide-1 (GLP-1)
timeFrame: Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
measure: CD26
timeFrame: Before the meal or at baseline (t=-15 or -1 min) on study days 1 and 2
measure: Surrogate markers of lipolysis
timeFrame: Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
measure: Mean heart rate
timeFrame: Before the meal and for 4 hours after (t=-15 through t=240 min) on study days 1 and 2
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Jessica R Wilson, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: