Effect of DPP4 Inhibition on Growth Hormone Secretion
This study tests the following hypotheses:
Aim 1A: 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 1B: Test the hypothesis that decreased degradation of GHRH during acute DPP4 inhibition will result in increased forearm blood flow through a GH-dependent mechanism 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.
|Study Design:||Time Perspective: Prospective|
|Official Title:||The Effect of Dipeptidyl Peptidase IV Inhibition on Growth Hormone-Mediated Vasodilation|
- stimulated peak growth hormone level [ Time Frame: Change from Baseline in Growth Hormone level at 1 week ] [ Designated as safety issue: No ]Subjects undergo two study days separated by at least one week. On one study day they will receive study drug and on another placebo, in a randomized double-blind fashion. Growth hormone level will be stimulated using arginine on each study day. Growth hormone levels will be assessed 7 times during a 3 hour period following arginine stimulation. The peak Growth Hormone level will be obtained.
- forearm blood flow [ Time Frame: Change from Baseline in Forearm Blood Flow at 1 week ] [ Designated as safety issue: No ]Subjects undergo two study days separated by at least one week. On one study day they will receive study drug and on another placebo, in a randomized double-blind fashion. Forearm blood flow will be assessed at each visit.
- Venous Blood Sampling [ Time Frame: Change from Baseline in Venous Blood Samples ] [ Designated as safety issue: No ]Subjects undergo two study days separated by at least one week. On one study day they will receive study drug and on another placebo, in a randomized double-blind fashion. Venous blood samples will be obtained at each visit. These samples will be analyzed for markers of cardiovascular and metabolic risk.
Biospecimen Retention: Samples With DNA
Samples to be retained include: extracted DNA; plasma samples
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||July 2013|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Healthy Lean Adults
In Aim 1: Healthy Lean adults are randomized in a double-blinded cross over fashion to sitagliptin versus placebo.
In Aim 2: Healthy Lean adults receive sitagliptin and are randomized in a double-blinded cross over fashion to pre-treatment with either pegvisomant versus placebo.
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.
Other Name: JanuviaDrug: Pegvisomant
During Aim 2, given 72 hours prior to one of two study days
Other Name: Somavert
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.
|United States, Tennessee|
|Vanderbilt University Medical Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: Stacy Gilbert, RN 615-322-8837 email@example.com|
|Principal Investigator: Jessica K Devin, MD, MSCI|
|Principal Investigator:||Jessica K Devin, MD, MSCI||Vanderbilt University|