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

This study has been completed.
Sponsor:
Collaborator:
VA Puget Sound Health Care System
Information provided by (Responsible Party):
Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier:
NCT00990184
First received: October 2, 2009
Last updated: October 22, 2012
Last verified: October 2012
  Purpose

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).


Condition Intervention Phase
Impaired Fasting Glucose
Prediabetes
Drug: Colesevelam
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Seattle Institute for Biomedical and Clinical Research:

Primary Outcome Measures:
  • Acute Insulin Response (AIRg) to Intravenous Glucose [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Insulin Sensitivity [ Time Frame: Baseline and 8 weeks ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Rate of fall of glucose in the blood


Enrollment: 21
Study Start Date: September 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Colesevelam Hydrochloride Drug: Colesevelam
colesevelam HCl 3.75 g once daily orally with the evening meal
Other Name: colesevelam HCl
Other: placebo
tablet (s) orally given with evening meal
Other Name: placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990184

Sponsors and Collaborators
Seattle Institute for Biomedical and Clinical Research
VA Puget Sound Health Care System
Investigators
Principal Investigator: Steven E Kahn, MB CHB VA Puget Sound HealthCare System
  More Information

No publications provided by Seattle Institute for Biomedical and Clinical Research

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Seattle Institute for Biomedical and Clinical Research
ClinicalTrials.gov Identifier: NCT00990184     History of Changes
Other Study ID Numbers: 1.2
Study First Received: October 2, 2009
Results First Received: February 1, 2012
Last Updated: October 22, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Seattle Institute for Biomedical and Clinical Research:
Impaired Fasting Glucose
PreDiabetes

Additional relevant MeSH terms:
Glucose Intolerance
Prediabetic State
Insulin Resistance
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Hyperinsulinism
Colesevelam
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 01, 2014