Study to Evaluate the Effects of Colesevelam on Insulin Sensitivity and ß-Cell Function in Subjects With Impaired Fasting Glucose (Prediabetes)

NCT ID: NCT00990184

Last Updated: 2012-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2010-10-31

Brief Summary

The objective of this study is to determine the effect of 8 weeks of treatment with colesevelam HCl 3.75 g once daily with the evening meal on ß-cell function by evaluating the acute insulin response (AIRg) to an intravenous glucose load in subjects with prediabetes (impaired fasting glucose).

Detailed Description

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.

Conditions

Impaired Fasting Glucose; Prediabetes

Keywords

Impaired Fasting Glucose; PreDiabetes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Colesevelam Hydrochloride

Group Type: EXPERIMENTAL

Colesevelam

Intervention Type: DRUG

colesevelam HCl 3.75 g once daily orally with the evening meal

placebo

Intervention Type: OTHER

tablet (s) orally given with evening meal

Interventions

Colesevelam

colesevelam HCl 3.75 g once daily orally with the evening meal

Intervention Type: DRUG

placebo

tablet (s) orally given with evening meal

Intervention Type: OTHER

Other Intervention Names

colesevelam HCl

Eligibility Criteria

Inclusion Criteria

• Males or females (postmenopausal, surgically sterile or using double-barrier method of contraception), aged 18-75 years, FPG 100-115 mg/dl at screening (average of 2 measurements during screening; no individual measurement outside of the range 92-125 mg/dl)
• In good health as determined by past medical history, physical examination, electrocardiogram, laboratory tests and urinalysis
• HbA1c <6.5% at screening
• Body mass index (BMI) in the range of 22-40 kg/m2 inclusive and with a stable (+/-2.5 kg) weight for the last 6 months
• Subjects must be willing to:

• Maintain prior exercise and dietary habits throughout the study
• Comply with all study requirements
• Provide written informed consent

Exclusion Criteria

• Pregnant or lactating females
• Patients diagnosed with type 2 diabetes or that have taken glucose-lowering agents or insulin, except during pregnancy
• Chronic oral or parenteral corticosteroid treatment (>7 consecutive days of treatment) within 8 weeks prior to screening
• HIV protease inhibitors
• Warfarin or phenytoin use
• Triglycerides >500 mg/dl
• History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
• History of dysphagia, swallowing disorders or intestinal motility disorder
• History of pancreatitis
• Uncontrolled hypothyroidism
• Individuals with clinical hepatic disease or liver function tests greater than ≥2 times upper limits of normal within 30 days preceding the first dose of study drug
• On a weight loss program with ongoing weight loss, or starting an intensive exercise program within 4 weeks of study initiation
• Current or prior (within the past 3 months) treatment with a bile acid sequestrant (colesevelam, colestipol, colestimide, or cholestyramine)
• Use of any investigational drug in the last 30 days
• Donation of one unit (500 ml) or more of blood, significant blood loss equaling at least one unit of blood within the past 2 weeks or a blood transfusion within 8 weeks prior to screening
• Employment by the research center

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Puget Sound Health Care System

FED

Sponsor Role: collaborator

Seattle Institute for Biomedical and Clinical Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven E Kahn, MB CHB

Role: PRINCIPAL_INVESTIGATOR

VA Puget Sound Health Care System

Countries

United States

References

Marina AL, Utzschneider KM, Wright LA, Montgomery BK, Marcovina SM, Kahn SE. Colesevelam improves oral but not intravenous glucose tolerance by a mechanism independent of insulin sensitivity and beta-cell function. Diabetes Care. 2012 May;35(5):1119-25. doi: 10.2337/dc11-2050. Epub 2012 Mar 23.

Reference Type: DERIVED

PMID: 22446171 (View on PubMed)

Other Identifiers

1.2

Identifier Type: -

Identifier Source: org_study_id