Effect of DPP4 Inhibition on Growth Hormone Secretion

• Status: Completed
• Trial end date: 2017-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This study tests the following hypotheses:

Aim 1: Test the hypothesis that acute dipeptidyl peptidase 4 (DPP4) inhibition with the currently available anti-diabetic drug, sitagliptin, will increase stimulated growth hormone (GH) secretion in healthy lean adults by decreasing the degradation of growth hormone releasing hormone (GHRH).

Aim 2: Test the hypothesis that decreased degradation of GHRH during acute DPP4 inhibition will result in an increase in endothelium-dependent vasodilation mediated by GH and independent from GLP1 (glucagon like peptide-1) in healthy lean adults.

This study promises to provide novel data regarding how this increasingly used class of anti-diabetic drugs affects the pituitary GH axis and could affect blood vessel relaxation. Growth hormone levels are low in the setting of obesity and pre-diabetes. A further study may evaluate the effect of chronic DPP4 inhibitor therapy in a population of patients with obesity and pre-diabetes.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Vanderbilt University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Treatments: Hormones; omega-N-Methylarginine; Sitagliptin Phosphate

Criteria

Inclusion Criteria:

• Age 18 to 40 years inclusive

• BMI ≤ 25 kg/m2

• For female subjects:

Status-post surgical sterilization, or If of child-bearing potential, utilization of a barrier method of birth control following negative serum pregnancy test at screening visit and on every study day

Exclusion Criteria:

• Smoking

• Type 1 or Type 2 Diabetes Mellitus, as defined by a fasting glucose of 126 mg/dL or greater at the time of screening visit or the use of anti-diabetic medication

• Hypertension, as defined by an untreated seated systolic blood pressure (SBP) greater than 140 mmHg and/or an untreated diastolic blood pressure (DBP) greater than 90 mmHg at the time of screening visit or the use of anti-hypertensive medication

• History of reported or recorded hypoglycemia (plasma glucose < 70 mg/dL)

• Pregnancy and/or Breast-Feeding

• Use of any medication other than multivitamin, including use of transdermal as well as oral hormone replacement therapy or use of oral contraceptive therapy

• Anemia defined as hematocrit <35% at screening visit

• Cardiovascular or cerebrovascular disease, including history of myocardial infarction, history of congestive heart failure, history of stroke

• Pulmonary Hypertension

• Abnormal thyroid hormone levels (TSH) at the time of screening visit

• Abnormal serum insulin like growth factor-1 (IGF-1) at the time of screening visit

• Impaired renal function, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2

• Impaired hepatic function (alanine or aspartate transaminase > 2 X upper limit of normal range)

• Treatment with an investigational drug in the 1 month preceding the study