Effect of DPP4 Inhibition on Growth Hormone Secretion
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ClinicalTrials.gov Identifier: NCT01701973 |
Recruitment Status
:
Completed
First Posted
: October 5, 2012
Last Update Posted
: June 29, 2017
|
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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 or disease | Intervention/treatment | Phase |
---|---|---|
Obesity | Drug: Sitagliptin Drug: Pegvisomant Drug: Placebo Drug: L-NMMA Drug: Exendin 9-39 | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 43 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Other |
Official Title: | The Effect of Dipeptidyl Peptidase IV Inhibition on Growth Hormone-Mediated Vasodilation |
Study Start Date : | January 2013 |
Actual Primary Completion Date : | May 2017 |
Actual Study Completion Date : | May 2017 |

Arm | Intervention/treatment |
---|---|
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
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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)
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- Aim 1: stimulated peak growth hormone level [ Time Frame: Change from Baseline in Growth Hormone level ]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 ]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 ]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.

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Ages Eligible for Study: | 18 Years to 40 Years (Adult) |
Sexes Eligible for Study: | All |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01701973
United States, Tennessee | |
Vanderbilt University Medical Center | |
Nashville, Tennessee, United States, 37232 |
Principal Investigator: | Jessica K Devin, MD, MSCI | Vanderbilt University Medical Center |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Jessica Koch Devin, Assistant Professor, Vanderbilt University |
ClinicalTrials.gov Identifier: | NCT01701973 History of Changes |
Other Study ID Numbers: |
120078 1K23HL119602 ( U.S. NIH Grant/Contract ) |
First Posted: | October 5, 2012 Key Record Dates |
Last Update Posted: | June 29, 2017 |
Last Verified: | June 2017 |
Keywords provided by Jessica Koch Devin, Vanderbilt University:
obesity growth hormone |
Additional relevant MeSH terms:
Hormones Sitagliptin Phosphate omega-N-Methylarginine Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Hypoglycemic Agents |
Incretins Dipeptidyl-Peptidase IV Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |