Effect of DPP4 Inhibition on Growth Hormone Secretion

This study is currently recruiting participants.
Verified November 2013 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Jessica Koch Devin, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01701973
First received: October 3, 2012
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention
Obesity
Drug: Sitagliptin
Drug: Pegvisomant

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: The Effect of Dipeptidyl Peptidase IV Inhibition on Growth Hormone-Mediated Vasodilation

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 14
Study Start Date: January 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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.

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.
Other Name: Januvia
Drug: Pegvisomant
During Aim 2, given 72 hours prior to one of two study days
Other Name: Somavert

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Fourteen healthy, non-smoking, lean adults

Criteria

Inclusion Criteria:

  • Age 18 to 40 years inclusive
  • 50% Male; 50% Female
  • 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 β-HCG 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 SBP greater than 140 mmHg and/or an untreated 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 IGF-1 at the time of screening visit
  • Impaired renal function, defined as eGFR <60 mL/min/1.73M2
  • Impaired hepatic function (AST or ALT > 2 X upper limit of normal range)
  • Treatment with an investigational drug in the 1 month preceding the study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01701973

Locations
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Stacy Gilbert, RN    615-322-8837    stacy.gilbert@vanderbilt.edu   
Principal Investigator: Jessica K Devin, MD, MSCI         
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Jessica K Devin, MD, MSCI Vanderbilt University
  More Information

No publications provided

Responsible Party: Jessica Koch Devin, Instructor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01701973     History of Changes
Other Study ID Numbers: 120078
Study First Received: October 3, 2012
Last Updated: November 22, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
obesity
growth hormone

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hormones
Sitagliptin
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents

ClinicalTrials.gov processed this record on April 17, 2014