Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Incretins in Impaired Fasting Glucose

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00364377
Recruitment Status : Completed
First Posted : August 15, 2006
Results First Posted : December 6, 2011
Last Update Posted : December 6, 2011
Sponsor:
Information provided by (Responsible Party):
Adrian Vella, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE August 14, 2006
First Posted Date  ICMJE August 15, 2006
Results First Submitted Date  ICMJE April 4, 2011
Results First Posted Date  ICMJE December 6, 2011
Last Update Posted Date December 6, 2011
Study Start Date  ICMJE August 2006
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 1, 2011)
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
Original Primary Outcome Measures  ICMJE
 (submitted: August 14, 2006)
Lowering of Fasting Glucose
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Incretins in Impaired Fasting Glucose
Official Title  ICMJE The Role of Incretins in the Pathogenesis of Fasting and Postprandial Glucose Metabolism in People With Impaired Fasting Glucose
Brief Summary People with high fasting glucose can develop type 2 diabetes with the passage of time. This study is being done to determine the effect of a novel medication in people with this elevated fasting glucose. Sitagliptin is a substance that raises levels of a hormone normally found in the blood. This hormone, called glucagon-like peptide-1 (GLP-1), is normally released by the intestine in response to the presence of food. This hormone acts like a messenger between the intestine and the pancreas to raise insulin levels, and therefore, lower blood sugars. Sitagliptin is effective in people with diabetes, however, this study is being done to determine if Sitagliptin is effective in people with high fasting glucose who do not yet have diabetes.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Pre-diabetes
Intervention  ICMJE
  • Drug: Sitagliptin
    100 mg once daily
    Other Name: Januvia
  • Other: Placebo
    once daily for duration of the study
Study Arms  ICMJE
  • Active Comparator: Sitagliptin
    People with impaired fasting glucose randomized to treatment with sitagliptin 100 mg once daily.
    Intervention: Drug: Sitagliptin
  • Placebo Comparator: Placebo
    People with impaired fasting glucose randomized to treatment with placebo once daily.
    Intervention: Other: Placebo
Publications * Bock G, Dalla Man C, Micheletto F, Basu R, Giesler PD, Laugen J, Deacon CF, Holst JJ, Toffolo G, Cobelli C, Rizza RA, Vella A. The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose. Clin Endocrinol (Oxf). 2010 Aug;73(2):189-96. doi: 10.1111/j.1365-2265.2009.03764.x. Epub 2009 Dec 18.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 1, 2011)
22
Original Enrollment  ICMJE
 (submitted: August 14, 2006)
24
Actual Study Completion Date  ICMJE December 2008
Actual Primary Completion Date December 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00364377
Other Study ID Numbers  ICMJE 06-002673
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Adrian Vella, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Adrian Vella, M.D. Mayo Clinic
PRS Account Mayo Clinic
Verification Date November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP