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

Primary Purpose

Impaired Fasting Glucose, Prediabetes

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Colesevelam
placebo
Sponsored by
Seattle Institute for Biomedical and Clinical Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Impaired Fasting Glucose focused on measuring Impaired Fasting Glucose, PreDiabetes

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Colesevelam Hydrochloride

    Arm Description

    Outcomes

    Primary Outcome Measures

    Acute Insulin Response (AIRg) to Intravenous Glucose
    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
    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
    Rate of fall of glucose in the blood

    Full Information

    First Posted
    October 2, 2009
    Last Updated
    October 22, 2012
    Sponsor
    Seattle Institute for Biomedical and Clinical Research
    Collaborators
    VA Puget Sound Health Care System
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00990184
    Brief Title
    Study to Evaluate the Effects of Colesevelam on Insulin Sensitivity and ß-Cell Function in Subjects With Impaired Fasting Glucose (Prediabetes)
    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 Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2012
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2009 (undefined)
    Primary Completion Date
    October 2010 (Actual)
    Study Completion Date
    October 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Seattle Institute for Biomedical and Clinical Research
    Collaborators
    VA Puget Sound Health Care System

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Impaired Fasting Glucose, Prediabetes
    Keywords
    Impaired Fasting Glucose, PreDiabetes

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Single Group Assignment
    Masking
    Participant
    Allocation
    N/A
    Enrollment
    21 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Colesevelam Hydrochloride
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Colesevelam
    Other Intervention Name(s)
    colesevelam HCl
    Intervention Description
    colesevelam HCl 3.75 g once daily orally with the evening meal
    Intervention Type
    Other
    Intervention Name(s)
    placebo
    Intervention Description
    tablet (s) orally given with evening meal
    Primary Outcome Measure Information:
    Title
    Acute Insulin Response (AIRg) to Intravenous Glucose
    Description
    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.
    Time Frame
    Baseline and 8 weeks
    Secondary Outcome Measure Information:
    Title
    Insulin Sensitivity
    Description
    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.
    Time Frame
    Baseline and 8 weeks
    Title
    Glucose Disappearance Rate
    Description
    Rate of fall of glucose in the blood
    Time Frame
    Baseline and 8 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Steven E Kahn, MB CHB
    Organizational Affiliation
    VA Puget Sound Health Care System
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    22446171
    Citation
    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.
    Results Reference
    derived

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

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