NCT01701973

Effect of DPP4 Inhibition on Growth Hormone Secretion

The Effect of Dipeptidyl Peptidase IV Inhibition on Growth Hormone-Mediated Vasodilation

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 44 (actual)
• Sponsor: Vanderbilt University · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

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.

Detailed description

Growth hormone secretion is low in patients with obesity, insulin resistance, and hyperlipidemia. GH therapy in these populations and others has been limited by side effects which include hyperglycemia. Another strategy to increase GH secretion is to enhance pulsatile GH secretion by growth hormone releasing hormone. Growth hormone releasing hormone (GHRH) has a half life of 5 minutes due to its rapid inactivation by DPP4. An alternative strategy to increase endogenous GH secretion is by inhibiting degradation of GHRH by DPP4. DPP4 inhibitors are currently approved therapies for the treatment of hyperglycemia in patients with type 2 diabetes mellitus. They additionally cause blood vessel relaxation. We therefore propose to test the hypothesis that DPP4 inhibition simultaneously enhances GH secretion while improving blood glucoses and vascular function in patient populations with low GH and increased cardiovascular risk. These preliminary aims serve primarily as a novel "proof of concept" study to define the effect of acute pharmacologic DPPIV inhibition on stimulated GH secretion.

Conditions

• Obesity

Interventions

Type	Name	Description
DRUG	Sitagliptin	During Aim 1, given on one of two study days (other study day subjects receive placebo.) During Aim 2, given during both of two study days.
DRUG	Pegvisomant	During Aim 2, given 72 hours prior to one of two study days (Group B subjects only)
DRUG	Placebo	During Aim 1, given on one of two study days (other study day subjects receive sitagliptin.) During Aim 2, given on one of two study days (other study day subjects receive either L-NMMA, pegvisomant, or Exendin 9-39 pending their group assignment)
DRUG	L-NMMA	During Aim 2, given during one of two study days (Group A subjects only)
DRUG	Exendin 9-39	During Aim 2, given during one of two study days (Group C subjects only)

Timeline

• Start date: 2013-01-01
• Primary completion: 2017-05-01
• Completion: 2017-05-01
• First posted: 2012-10-05
• Last updated: 2018-05-29
• Results posted: 2018-05-29

Locations

1 site across 1 country: United States