Clinical trial NCT00947011: Dipeptidyl Peptidase-4 Inhibition on Glucagon-like Peptide-1 (GLP-1)
Official title: The Effect of Dipeptidyl Peptidase-4 Inhibition on GLP-1 Induced Insulin Secretion and Glucose Turnover During Mild Stable Hyperglycemia in Young and Old Normal Volunteers
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Glucose Homeostasis
Keywords: Healthy volunteers
GLP-1
Januvia
Sitagliptin
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2009-07-27
Enrollment: 12
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: This research is being done to evaluate the effect of glucagon-like peptide-1 (GLP-1, a naturally occurring hormone) on insulin release and to examine whether there is extra insulin release when GLP-1 is not allowed to be rapidly inactivated.

Detailed description: The purpose of the present proposal is to 1) examine the role of dipeptidyl peptidase (DPP-4) inhibition on insulin release during a hyperglycemic clamp while GLP-1 is being infused and, 2) further elucidate the role of the metabolite of GLP-1, that is GLP-1 9-36 amide (GLP-1m). During stable and very reproducible elevated plasma glucose levels the effect of increased active incretin levels with DPP-4 inhibitors should result in increased plasma insulin levels. Therefore the aim of this protocol is to document whether plasma insulin levels are increased following GLP-1 infusion in the presence or absence of DPP-4 inhibitors. Additionally, the investigators have shown that some improvement in glucose homeostasis during GLP-1 administration is due in part to the metabolite of GLP-1, i.e. GLP-1 (9-36) amide (GLP-1m). Therefore, the investigators will also test the role of the latter by infusing GLP-1m when the volunteers are being treated with DPP-4 inhibitors.

Eligibility criteria: Inclusion Criteria:

* Hct level of at least 34% for women and 36% for men
* Women of non-bearing potential and women of childbearing potential using adequate contraception
* Serum creatine level of less than 1.7 mg/dl
* Four groups:

  * Age 21-45 (BMI between 18.50-24.99) \& (BMI between 30-35)
  * Age greater than 65 years (BMI between 18.50-24.99) \& (BMI between 30-35)

Exclusion Criteria:

* Pregnant and/or lactating females
* Women of childbearing potential not willing to use adequate contraception
* Hct below inclusion criteria
* Serum creatine level greater than 1.8 mg/dl
* Age less than 21 and age between 46-64
* Diabetes mellitus
* BMI less than 18 and BMI greater than 35

Primary outcomes:
measure: Insulin Release Rate and Hepatic Glucose Release
timeFrame: One year
Secondary outcomes:
measure: Peripheral Glucose Utilization and Peripheral Glucagon Release
timeFrame: one year
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Dariush Elahi, PhD
role: PRINCIPAL_INVESTIGATOR
References: