Effect of DPP4 Inhibition on Growth Hormone Secretion

May 25, 2018 updated by: Jessica Koch Devin, Vanderbilt University

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 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
44

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
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 Names:
  • 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 Names:
  • sugar pill
Drug: L-NMMA
During Aim 2, given during one of two study days (Group A subjects only)
Other Names:
  • L-N-Monomethyl-arginine
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.
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 Names:
  • 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 Names:
  • sugar pill
Drug: Pegvisomant
During Aim 2, given 72 hours prior to one of two study days (Group B subjects only)
Other Names:
  • Somavert
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.
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 Names:
  • 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 Names:
  • sugar pill
Drug: Exendin 9-39
During Aim 2, given during one of two study days (Group C subjects only)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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.
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: 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
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.
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 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.
Forearm blood flow was determined by strain gauge plethysmography. The percent change from baseline was determined at each timepoint.
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
Time Frame: Percent change from baseline in forearm blood flow at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes.
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.
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 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
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.
Percent change from baseline in forearm vascular resistance at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Aim 1: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels
Time Frame: baseline and every 30 minutes for 180 minutes
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.
baseline and every 30 minutes for 180 minutes
Aim 2: Venous Blood Sampling for Tissue Plasminogen Activator (TPA) Activity Levels
Time Frame: baseline and every 30 minutes until 180 minutes
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.
baseline and every 30 minutes until 180 minutes
Aim 2: Measurement of Growth Hormone (GH) Levels
Time Frame: baseline and every 30 minutes until 180 minutes
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.
baseline and every 30 minutes until 180 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vanderbilt University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jessica K Devin, MD, MSCI, Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 3, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 3, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 5, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 29, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 25, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 120078
  • 1K23HL119602 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Obesity

Clinical Trials on Sitagliptin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings