Effect of DPP4 Inhibition on Growth Hormone Secretion

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Vanderbilt University
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Jessica Koch Devin, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01701973
First received: October 3, 2012
Last updated: July 10, 2014
Last verified: July 2014

October 3, 2012
July 10, 2014
January 2013
July 2015   (final data collection date for primary outcome measure)
  • Aim 1: stimulated peak growth hormone level [ Time Frame: Change from Baseline in Growth Hormone level ] [ Designated as safety issue: No ]
    Subjects undergo two study days separated by a washout period. 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 during a 3 hour period following arginine stimulation. The peak Growth Hormone level will be obtained.
  • Aim 2: forearm blood flow [ Time Frame: Change from Baseline in Forearm Blood Flow ] [ Designated as safety issue: No ]
    Subjects undergo two study days separated by a washout period. 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.
  • stimulated peak growth hormone secretion [ Time Frame: day of study drug administration ] [ 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 secretion 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.
  • forearm blood flow [ Time Frame: day of study drug administration ] [ 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 secretion will be stimulated using arginine on each study day. Forearm blood flow will be assessed 7 times during a 3 hour period following arginine stimulation.
Complete list of historical versions of study NCT01701973 on ClinicalTrials.gov Archive Site
Venous Blood Sampling [ Time Frame: Change from Baseline in Venous Blood Samples ] [ Designated as safety issue: No ]
In Aim 1 and 2, subjects undergo two study days separated by a washout period. 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.
Venous Blood Sampling [ Time Frame: On each Study Day (day of study drug administration) ] [ 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 secretion will be stimulated using arginine on each study day. Venous blood samples will be obtained at baseline and 7 times during a 3 hour period following arginine stimulation. These samples will be analyzed for markers of cardiovascular and metabolic risk.
Not Provided
Not Provided
 
Effect of DPP4 Inhibition on Growth Hormone Secretion
The Effect of Dipeptidyl Peptidase IV Inhibition on Growth Hormone-Mediated Vasodilation

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 GLP-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.

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.

Interventional
Phase 0
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Obesity
  • 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 (Group B subjects only)
    Other Name: Somavert
  • 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)
    Other Name: sugar pill
  • Drug: L-NMMA
    During Aim 2, given during one of two study days (Group A subjects only)
    Other Name: NG-Monomethyl-L-arginine
  • Drug: Exendin 9-39
    During Aim 2, given during one of two study days (Group C subjects only)
  • Group A (14 healthy subjects)

    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 L-NMMA versus placebo.

    Interventions:
    • Drug: Sitagliptin
    • Drug: Placebo
    • Drug: L-NMMA
  • Group B (14 healthy subjects)

    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.

    Interventions:
    • Drug: Sitagliptin
    • Drug: Pegvisomant
    • Drug: Placebo
  • Group C (14 healthy subjects)

    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 Exendin 9-39 versus placebo.

    Interventions:
    • Drug: Sitagliptin
    • Drug: Placebo
    • Drug: Exendin 9-39
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
42
December 2015
July 2015   (final data collection date for primary outcome measure)

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 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
Both
18 Years to 40 Years
Yes
United States
 
NCT01701973
120078, 1K23HL119602
Yes
Jessica Koch Devin, Vanderbilt University
Vanderbilt University
  • National Institutes of Health (NIH)
  • National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Jessica K Devin, MD, MSCI Vanderbilt University
Vanderbilt University
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP