Study to Evaluate the Effects of Colesevelam on Insulin Sensitivity and ß-Cell Function in Subjects With Impaired Fasting Glucose (Prediabetes)
|ClinicalTrials.gov Identifier: NCT00990184|
Recruitment Status : Completed
First Posted : October 6, 2009
Results First Posted : November 21, 2012
Last Update Posted : November 21, 2012
|Condition or disease||Intervention/treatment||Phase|
|Impaired Fasting Glucose Prediabetes||Drug: Colesevelam Other: placebo||Phase 3|
Colesevelam is a bile acid sequestrant that was initially approved for treatment of patients with dyslipidemia. Subsequently it was observed that patients with type 2 diabetes receiving this medication had improved glucose control. However, the mechanism(s) by which it lowers glucose concentrations has not been determined.
Glucose metabolism is enhanced following oral nutrient ingestion by the action of the incretin hormones. The two major incretin hormones are the peptides glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which are released from the intestinal tract wall in response to a meal. Of these two peptides, GLP-1 appears to be more important in regulating glucose metabolism. In the presence of elevated plasma glucose, GLP-1 promotes insulin release from the ß-cells of the pancreas. GLP-1 also suppresses glucagon release, and thereby inhibits hepatic glucose output. Administration of GLP-1 by infusion or by subcutaneous injection has been shown to improve glucose tolerance in type 2 diabetic patients.
The purpose of this study is therefore to determine in a cohort of individuals with prediabetes, who have an elevated fasting plasma glucose and are at increased risk of developing type 2 diabetes, whether the glucose lowering properties of colesevelam occur by it improving insulin sensitivity, islet ß-cell function or both. Further, by assessing the effect of colesevelam on incretin hormone release, it will be possible to determine whether any improvement in islet ß-cell function is due to enhanced incretin stimulation.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Official Title:||A Single-Blind Study to Evaluate the Effects of Colesevelam on Insulin Sensitivity and ß-Cell Function in Subjects With Impaired Fasting Glucose (Prediabetes)|
|Study Start Date :||September 2009|
|Actual Primary Completion Date :||October 2010|
|Actual Study Completion Date :||October 2010|
|Experimental: Colesevelam Hydrochloride||
colesevelam HCl 3.75 g once daily orally with the evening meal
Other Name: colesevelam HCl
tablet (s) orally given with evening meal
- Acute Insulin Response (AIRg) to Intravenous Glucose [ Time Frame: Baseline and 8 weeks ]Increase in insulin following glucose injection. AIRg is measured as the magnitude of the insulin response to an intravenous glucose injection calculated over the 10 minutes following glucose administration.
- Insulin Sensitivity [ Time Frame: Baseline and 8 weeks ]Tissue response to circulating insulin in the blood. Insulin sensitivity is measured using a mathematical model that quantifies the fractional rate of change in glucose concentrations per unit of insulin. Low values are insulin resistant and high values are insulin sensitive. *Please note: the "-1" in the Unit of Measure should be a superscripted value.
- Glucose Disappearance Rate [ Time Frame: Baseline and 8 weeks ]Rate of fall of glucose in the blood
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00990184
|Principal Investigator:||Steven E Kahn, MB CHB||VA Puget Sound Healthcare System|