Trial · Interventional

CompletedPhase 4Results postedRegistry data

Effect of DPP4 Inhibition on Growth Hormone Secretion

NCTNCT01701973Other id120078Other id1K23HL119602

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 4
Enrollment: 44 participants (actual)
Sponsor: Vanderbilt University · Other
Design: Randomized · Double masking
Countries: 1 country
United States
Start: Jan 2013
Primary completion: May 2017
Completion: May 2017
First posted: 5 Oct 2012 (estimated)
Last update posted: 29 May 2018
Conditions: Obesity

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

201320142015201620172018

Ph 4
Effect of DPP4 Inhibition on Growth Hormone Secretion
NCT01701973
Jan 2013 to May 2017

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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 GLP1 (glucagon like peptide-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.

Interventions

SitagliptinDrug
PegvisomantDrug
PlaceboDrug
L-NMMADrug
Exendin 9-39Drug

Arms3

Other
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 LNMMA (L-N-Monomethyl-arginine) versus placebo.
Other
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.
Other
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.

Primary outcomes5

Outcomes the sponsor listed as primary.

Aim 1: Stimulated Peak Growth Hormone Level
Time frame · Growth Hormone Level at 30 minutes (i.e. at completion of arginine infusion), 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes
Registry description
Subjects underwent two study days separated by a washout period. On one study day they will receive sitagliptin and on another placebo, in a randomized double-blind fashion. Growth hormone secretion was stimulated using arginine (30 grams i.v. over 30 minutes) on each study day. Growth hormone levels were assessed during a 3 hour period following arginine stimulation.
Aim 1: Percent Change From Baseline in Forearm Vascular Resistance
Time frame · Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes
Registry description
Forearm blood flow was determined by strain gauge plethysmography. Forearm vascular resistance was then calculated by dividing this into mean arterial pressure. The percent change from baseline was determined at each timepoint.
Aim 1: Percent Change From Baseline in Forearm Blood Flow
Time frame · Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.
Registry description
Forearm blood flow was determined by strain gauge plethysmography. The percent change from baseline was determined at each timepoint.
Aim 2: Percent Change From Baseline in Forearm Blood Flow
Time frame · Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.
Registry description
Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit.
Aim 2: Percent Change From Baseline in Forearm Vascular Resistance
Time frame · Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes
Registry description
Subjects undergo two study days separated by a washout period. On one study day they will receive sitagliptin plus another study drug and on another sitagliptin plus placebo, in a randomized double-blind fashion. Forearm blood flow was assessed at each visit every 30 minutes for 3 hours. This was divided into mean arterial pressure to determine forearm vascular resistance.

Secondary outcomes(3)

Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels
Time frame · baseline and every 30 minutes for 180 minutes
Registry description
In Aim 1 subjects underwent two study days separated by a washout period. On one study day they received study drug and on another placebo, in a randomized double-blind fashion. Venous blood samples were obtained at each visit.
Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels
Time frame · baseline and every 30 minutes until 180 minutes
Registry description
Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Tissue plasminogen activator activity (tPA) was assessed at each visit.
Aim 2: Measurement of Growth Hormone (GH) Levels
Time frame · baseline and every 30 minutes until 180 minutes
Registry description
Subjects undergo two study days separated by a washout period. On one study day they received sitagliptin plus pegvisomant and on another sitagliptin plus placebo, in a randomized double-blind fashion. Growth hormone secretion following arginine stimulation was assessed at each visit. Growth hormone levels were determined using an assay that is not subject to interference by pegvisomant.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Growth Hormone Level at 30 minutes (i.e. at completion of arginine infusion), 45 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes

Aim 1: Stimulated Peak Growth Hormone Level

Group	Value (ng/ml)	Spread
Aim 1: Sitagliptin,Female Participants	5.2	4.2
Aim 1: Placebo, Female Participants	3.1	3.3
Aim 1: Sitagliptin, Male Participants	1.9	1.9
Aim 1: Placebo, Male Participants	2.0	2.3

Primary outcomeMean· Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes

Aim 1: Percent Change From Baseline in Forearm Vascular Resistance

Group	Value (percentage change from baseline)	Spread
Aim 1: Sitagliptin,Female Participants	-5.0677	18.56794
Aim 1: Placebo, Female Participants	-5.3498	19.60881
Aim 1: Sitagliptin, Male Participants	1.4929	21.57596
Aim 1: Placebo, Male Participants	-11.2235	13.60628

Primary outcomeMean· Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.

Aim 1: Percent Change From Baseline in Forearm Blood Flow

Group	Value (percent change from baseline)	Spread
Aim 1: Sitagliptin,Female Participants	0.4835	19.44436
Aim 1: Placebo, Female Participants	1.6458	19.42502
Aim 1: Sitagliptin, Male Participants	-.0238	23.86278
Aim 1: Placebo, Male Participants	9.2597	14.60368

Primary outcomeMean· Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.

Aim 2: Percent Change From Baseline in Forearm Blood Flow

Group	Value (percent change from baseline)	Spread
Aim 2: Sitagliptin and LNMMA, Female Participants	-0.71	6.75
Aim 2: Sitagliptin and Placebo, Females in LNMMA Group	-9.34	8.60
Aim 2: Sitagliptin and LNMMA, Male Participants	5.17	4.27
Aim 2: Sitagliptin and Placebo, Males in LNMMA Group	14.78	14.78
Aim 2: Sitagliptin and Pegvisomant, Female Participants	15.64	5.06
Aim 2: Sitagliptin & Placebo, Females in Pegvisomant Group	0.39	8.93
Aim 2: Sitagliptin and Exendin 9-39, Female Participants	-7.33	8.66
Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group	-0.98	12.08
Aim 2: Sitagliptin and Exendin 9-39, Male Participant	-7.59	NA
Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group	-22.67	NA

Primary outcomeMean· Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes

Aim 2: Percent Change From Baseline in Forearm Vascular Resistance

Group	Value (percent change from baseline)	Spread
Aim 2: Sitagliptin and LNMMA, Female Participants	-8.67	9.66
Aim 2: Sitagliptin and Placebo, Females in LNMMA Group	8.98	12.07
Aim 2: Sitagliptin and LNMMA, Male Participants	-9.87	0.82
Aim 2: Sitagliptin and Placebo, Males in LNMMA Group	-14.60	12.22
Aim 2: Sitagliptin and Pegvisomant, Female Participants	-20.00	3.67
Aim 2: Sitagliptin & Placebo,Females in Pegvisomant Group	-3.75	12.43
Aim 2: Sitagliptin and Exendin 9-39, Female Participants	5.30	8.19
Aim 2: Sitagliptin and Placebo, Females in Exendin 9-39 Group	4.53	12.62
Aim 2: Sitagliptin and Exendin 9-39, Male Participant	0.57	NA
Aim 2: Sitagliptin and Placebo, Male in Exendin 9-39 Group	27.77	NA

Secondary and other outcome results(3)

Secondary outcomeMean· baseline and every 30 minutes for 180 minutes

Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels

Group	Value (IU/ml)	Spread
Aim 1: Sitagliptin,Female Participants	0.30	0.05
Aim 1: Placebo, Female Participants	0.28	0.05
Aim 1: Sitagliptin, Male Participants	0.44	0.14
Aim 1: Placebo, Male Participants	0.22	0.07

Secondary outcomeMean· baseline and every 30 minutes until 180 minutes

Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels

Group	Value (IU/ml)	Spread
Aim 2: Sitagliptin and Placebo, Females in Pegvisomant Group	0.24	0.05
Aim 2: Sitagliptin and Pegvisomant, Female Participants	0.10	0.03

Secondary outcomeMean· baseline and every 30 minutes until 180 minutes

Aim 2: Measurement of Growth Hormone (GH) Levels

Group	Value (ng/mL)	Spread
Aim 2: Sitagliptin and Placebo, Females in Pegvisomant Group	2.99	1.60
Aim 2: Sitagliptin and Pegvisomant, Female Participants	4.27	2.19

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
SitagliptinHealthy lean adults completed a double blinded cross over study in which they took sitagliptin vs. placebo separated by a wash-out.	0 / 40	0 / 40	7 / 40
PlaceboHealthy lean adults completed a double blinded cross over study in which they took sitagliptin vs. placebo separated by a wash-out.	0 / 43	0 / 43	1 / 43
Sitagliptin Plus PegvisomantFive women from Aim 1 returned for an additional two study days in which they were randomized to sitagliptin plus placebo vs. sitagliptin plus pre-treatment with pegvisomant.	0 / 5	0 / 5	2 / 5
Sitagliptin Plus LNMMA9 participants from Aim 1 returned for an additional two study days in which they were randomized to sitagliptin plus placebo vs. sitagliptin plus L-N-mono-methylarginine (LNMMA).	0 / 9	0 / 9	0 / 9
Sitagliptin Plus Exendin 9-398 participants from Aim 1 returned for an additional two study days in which they were randomized to sitagliptin plus placebo vs. sitagliptin plus Exendin 9-39.	0 / 8	0 / 8	0 / 8

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

DerivedWilson JR, Brown NJ, Nian H, Yu C, Bidlingmaier M, Devin JK. Dipeptidyl Peptidase-4 Inhibition Potentiates Stimulated Growth Hormone Secretion and Vasodilation in Women. J Am Heart Assoc. 2018 Feb 25;7(5):e008000. doi: 10.1161/JAHA.117.008000. PMID 29478970

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years up to 40 Years
Healthy volunteers: Accepted

Inclusion and exclusion criteria, as posted

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 pregnancy test 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 systolic blood pressure (SBP) greater than 140 mmHg and/or an untreated diastolic blood pressure (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 insulin like growth factor-1 (IGF-1) at the time of screening visit * Impaired renal function, defined as estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m\^2 * Impaired hepatic function (alanine or aspartate transaminase \> 2 X upper limit of normal range) * Treatment with an investigational drug in the 1 month preceding the study

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