- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00364377
Incretins in Impaired Fasting Glucose
The Role of Incretins in the Pathogenesis of Fasting and Postprandial Glucose Metabolism in People With Impaired Fasting Glucose
Study Overview
Detailed Description
Impaired fasting glucose (IFG) confers a high risk of progression to diabetes. Its pathogenesis has been an area of active investigation, with defects in insulin and glucagon secretion as well as insulin action likely to play a role. Several studies have suggested that the prediabetic and diabetic state are associated with alterations in circulating incretin concentrations. More recently, a large study of non-diabetic individuals demonstrated decreased GLP-1 concentrations after a glucose challenge in individuals with prediabetes but concluded that defects in GLP-1 secretion were unrelated to insulin secretion. In impaired glucose tolerance (IGT), defects in incretin-induced insulin secretion coexist with defects in glucose induced insulin secretion.
Worsening degrees of glucose tolerance are associated with decreased insulin secretion for the prevailing insulin action. Moreover early glucagon suppression is impaired in IGT. Since GLP-1 is an insulin secretagogue and suppresses glucagon, it is conceivable that defects in GLP-1 secretion could contribute to the pathogenesis of pre-diabetes. Inhibition of Dipeptidyl Peptidase-4 (DPP-4), an enzyme which rapidly degrades the incretin hormones, has been shown to be a useful therapeutic strategy in type 2 diabetes. DPP-4 inhibitors increase (model-calculated) insulin secretion and decrease glucagon concentrations resulting in a lowering of fasting (and postprandial) glucose concentrations in people with type 2 diabetes. Their effects in people with IFG are less certain. However, DPP-4 inhibitors provide an opportunity to directly examine the contribution of abnormal incretin concentrations to the pathogenesis of IFG, by raising concentrations of endogenous incretin hormones.
The current experiments tested this hypothesis by measuring insulin secretion and action and fasting and postprandial glucose turnover before and after 8 weeks of therapy with a DPP-4 inhibitor.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Twenty four participants aged 35 to 70 years with impaired fasting glucose (100mg/dl-125 mg/dl) will be studied.
Inclusion Criteria:
- Males and females between the ages of 35-70.
- Good health as determined by past medical history,physical examination, vital signs, electrocardiogram and laboratory tests at the time of screening.
- Patients on diuretics or thyroid hormone therapy must be on a stable dose (at least 3 months prior to screening) and the maintenance dose may not be adjusted during the study.
Exclusion Criteria:
- Individuals with a body mass index less than 19 or greater than 40 kg/m^2, or a total weight > 130 kg, will be excluded from study.
- Subjects less than 35 years will not be studied in order to minimize the possibility of studying subjects with type 1 diabetes.
- No history of a) significant nephropathy, (i.e., plasma creatinine > 1.4 mg/dl in women and 1.5 mg/dl in men, and/or proteinuria); b) clinically significant atherosclerotic vascular disease (e.g., history of heart attack or angina); c) a known systemic illness.
- Pregnant or lactating females.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Sitagliptin
People with impaired fasting glucose randomized to treatment with sitagliptin 100 mg once daily.
|
100 mg once daily
Other Names:
|
PLACEBO_COMPARATOR: Placebo
People with impaired fasting glucose randomized to treatment with placebo once daily.
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once daily for duration of the study
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Lowering of Fasting Glucose
Time Frame: 8 weeks
|
fasting glucose taken as the mean of blood glucose measured at -30, -20, -10 and 0 minutes prior to each inpatient meal study
|
8 weeks
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Prediabetic State
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protease Inhibitors
- Incretins
- Dipeptidyl-Peptidase IV Inhibitors
- Sitagliptin Phosphate
Other Study ID Numbers
- 06-002673
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.
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