Pharmacogenetics of Response to Sitagliptin (PRS)

NCT06813014 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: HP-00111892
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study to find out how different people respond to a medication called sitagliptin. Sitagliptin is an FDA approved medication that is used to treat diabetes. We are asking for healthy, non-diabetic volunteers to participate in this 7-week study. If you agree to participate, you will take part in 2 clinic visits that are 4-6 weeks apart. At the clinic visits you will have an oral glucose tolerance test (OGTT) and other blood tests to see how your body processes glucose (sugar). An OGTT is a test in which your drink glucose and then blood samples are taken afterward at specific time points to measure glucose and insulin in your blood. Each clinic visit will last about 5 hours.

Conditions

Diabetes

Outcome Measures

Primary Outcomes (2)

• Sitagliptin-induced enhancement of early insulin secretion

  This represents the incretinomimetic effect of sitagliptin, which contributes importantly to the mechanism whereby DPP4is decrease HbA1c in T2D patients. Because histograms for sitagliptin-induced increase in our index of early insulin secretion (T30:T60) demonstrated a skewed distribution, we will apply a logarithmic transformation of data which yields a normal distribution. Thus, the drug effect is defined as: log(T30:T60 ins)sita - log(T30:T60 ins)control.

  6 weeks

• Sitagliptin-induced change in glucose tolerance

  Sitagliptin-induced change in glucose tolerance. This is a consequence of enhanced insulin secretion, which reflects most closely the desired effect of the drug to decrease plasma glucose and decrease HbA1c. Because histograms for sitagliptin-induced increase in our index of glucose tolerance (T30:T60) demonstrated a skewed distribution, we will apply a logarithmic transformation of data which yields a normal distribution. Thus, the drug effect is defined as: log(T30:T60 gluc)sita - log(T30:T60 gluc)control.

  6 weeks

Secondary Outcomes (5)

• Area under the curve for insulin concentration

  6 weeks

• Area under the curve for glucose concentration

  6 weeks

• Area under the curve for intact GIP

  6 weeks

• Area under the curve for intact GLP1

  6 weeks

• Area under the curve for C-peptide levels

  6 weeks

Other Outcomes (1)

• Parameters of a mathematical model (insulin secretion and glucose sensitivity of the β-cell

  6 weeks

Study Arms (2)

Sitagliptin

EXPERIMENTAL

Sitagliptin 100 mg given 2 hours prior to the oral glucose tolerance test

Procedure: Oral Glucose Tolerance Test

Placebo

PLACEBO COMPARATOR

Placebo given 2 hours prior to the oral glucose tolerance test

Procedure: Oral Glucose Tolerance Test

Interventions

Oral Glucose Tolerance Test PROCEDURE

Three hour glucose tolerance test

Placebo; Sitagliptin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: \>18 years old
• Members of Old Order Amish community in Lancaster, PA

You may not qualify if:

• Pregnancy (reproductive age women will undergo pregnancy tests immediately before receiving the drug)
• Diabetes: HbA1c \> 6.5% or fasting plasma glucose \>126 mg/dL
• Estimated glomerular filtration rates (eGFR) \<60 mL/min/1.73 m2
• Anemia: hematocrit \< 35%
• Thyroid status: TSH\<0.4 or TSH\>5.5
• ALT or AST in excess of 2X upper limit of normal
• Drugs that in the physician's judgment would alter response to sitagliptin
• Significant health issues that in the physician's judgment could increase the risk for participants.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Amish Research Clinic

Lancaster, Pennsylvania, 17602, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Officials

• Amber L Beitelshees, PharmD, MPH

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

• Simeon I Taylor, MD, PhD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amber L Beitelshees

CONTACT

14107060118; abeitels@som.umaryland.edu

Kamah Woelfel

CONTACT

KWoelfel@som.umaryland.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 6, 2025
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): November 1, 2031
• Study Completion (Estimated): December 1, 2032
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

US (1)