Effect of DPP4 Inhibition on Growth Hormone Secretion
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Obesity |
Drug: Sitagliptin Drug: Pegvisomant Drug: Placebo Drug: L-NMMA Drug: Exendin 9-39 |
Phase 0 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) |
| Official Title: | The Effect of Dipeptidyl Peptidase IV Inhibition on Growth Hormone-Mediated Vasodilation |
- 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.
- 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.
| Estimated Enrollment: | 42 |
| Study Start Date: | January 2013 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | July 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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. |
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: 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
|
|
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. |
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
|
|
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. |
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: 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: Exendin 9-39
During Aim 2, given during one of two study days (Group C subjects only)
|
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 |
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
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01701973
| 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 | |
| Principal Investigator: | Jessica K Devin, MD, MSCI | Vanderbilt University |
More Information
No publications provided
| Responsible Party: | Jessica Koch Devin, Assistant Professor, Vanderbilt University |
| ClinicalTrials.gov Identifier: | NCT01701973 History of Changes |
| Other Study ID Numbers: | 120078, 1K23HL119602 |
| Study First Received: | October 3, 2012 |
| Last Updated: | July 10, 2014 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
Keywords provided by Vanderbilt University:
|
obesity growth hormone |
Additional relevant MeSH terms:
|
Sitagliptin Dipeptidyl-Peptidase IV Inhibitors Enzyme Inhibitors Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Hypoglycemic Agents |
Incretins Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Protease Inhibitors |
ClinicalTrials.gov processed this record on March 01, 2015