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Effects of Colesevelam HCl On Bile Acid Kinetics

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ClinicalTrials.gov Identifier: NCT00476710
Recruitment Status : Completed
First Posted : May 22, 2007
Last Update Posted : April 1, 2015
Information provided by (Responsible Party):

Study Description
Brief Summary:
This project will compare the amount of bile acids and their kinetics in overweight and obese people with normal glucose metabolism, impaired glucose tolerance and frank type 2 diabetes. We hypothesize that bile acids will behave differently in these groups. We will also explore the effects of Colesevelam HCl, a medicine that lowers LDL cholesterol by binding bile acids, on bile acids in those groups. We hypothesize the drug may have different actions on bile acids in subjects with different degrees of abnormal glucose metabolism.

Condition or disease Intervention/treatment
Type 2 Diabetes Mellitus Impaired Glucose Tolerance Drug: Colesevelam HCl

Detailed Description:

Bile acids, which are synthesized from cholesterol in the liver, play a key role in digestion as they solubilize dietary lipids and aid their absorption in the digestive tract. While for many years bile acids have been characterized by this digestive role, recent research indicates that bile acids play other important roles. Because bile acids have been shown to act in signaling pathways that affect metabolism, there has been renewed interest in investigations of their effects. This study explores potential differences in bile acid kinetics based on insulin resistance or type 2 diabetes at baseline.

Colesevelam HCl is a bile acid sequestrant, which in addition to its primary role in lowering serum LDL-C levels, has secondarily been implicated in lowering blood glucose levels. This study explores the relationship between insulin resistance and type 2 diabetes and changes in bile acid pool sizes and kinetics with colesevelam treatment. Isotopically labeled bile acids will be administered to subjects before and after treatment with colesevelam and comparisons will be made in bile acid pool size, fractional turnover rate, and synthesis rate in the three study groups.

Study Design

Study Type : Observational
Actual Enrollment : 36 participants
Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Effects of Colesevelam HCl On Bile Acid Pools And Kinetic Parameters in Normal Subjects, Subjects With Impaired Glucose Tolerance, And Subjects With Type 2 Diabetes Mellitus
Study Start Date : May 2007
Primary Completion Date : April 2009
Study Completion Date : April 2009

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Groups and Cohorts

Group/Cohort Intervention/treatment
Normal Glucose Metabolism
Overweight and obese individuals that have normal glucose metabolism and their response to Colesevelam HCl
Drug: Colesevelam HCl
Impaired Glucose Tolerance
Overweight and obese individuals that have impaired glucose tolerance and their response to Colesevelam HCl
Drug: Colesevelam HCl
Frank type 2 diabetes
Overweight and obese individuals that have frank type 2 diabetes and their response to Colesevelam HCl
Drug: Colesevelam HCl

Outcome Measures

Primary Outcome Measures :
  1. Bile Acid Pool Size and Kinetic Parameters [ Time Frame: 60 days of treatment ]

Secondary Outcome Measures :
  1. Resting Metabolic Rate [ Time Frame: 60 days of treatment ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population
overweight and obese people with normal glucose metabolism, impaired glucose tolerance and frank type 2 diabetes

Inclusion Criteria:

  • Have given written informed consent
  • BMI 25-35 kg/m^2, inclusive
  • Normal liver and thyroid function
  • No history of liver, biliary, or intestinal disease

Diabetic Subjects

  • Diagnosed Type 2 Diabetes Mellitus
  • HbA1C = 6.7-10%

Normal Subjects

  • 2 hr OGTT glucose < 140 mg/dL
  • fasting glucose < 100 mg/dL
  • TG < 150 mg/dL
  • HDL cholesterol >= 40 mg/dL

Impaired Glucose Tolerance Subjects

  • 2 hr OGTT glucose >= 140 and < 200 mg/dL

Exclusion Criteria:

  • T1DM or history of diabetic ketoacidosis
  • treatment with blood pressure lowering therapy that has not been stable for three months before screening
  • colesevelam HCl, cholestyramine, or colestipol treatment for hyperlipidemia within the last three months
  • treatment with thiazolidinedione (TZD) at any time
  • treatment with insulin within past 6 months
  • treatment with antibiotics within last 3 months
  • extreme sportsmen
  • treatment with medication affecting liver or intestinal function within the last 3 months
  • allergic or toxic rxn to colesevelam HCl
  • history of dysphagia, swallowing disorders, or intestinal motility disorder
  • Serum Triglycerides > 500 mg/dL at visit 1
  • Serum LDL-C < 60 mg/dL at visit 1
  • any condition or therapy investigator believes not in subjects best interest
  • use of any investigational drug within 30 days before screening
  • chronic treatment with oral corticosteroids at any time or acute treatment within last three months
  • hyperthyroidism or treatment with thyroid hormone/levothyroxine
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00476710

United States, Texas
Diabetes & Glandular Disease Research Associates, Inc.
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Daiichi Sankyo, Inc.
University Medical Center Groningen
Diabetes & Glandular Disease Research Associates
Principal Investigator: Elizabeth J Murphy, MD KineMed, Inc.
Principal Investigator: Folkert Kuipers, PhD University Medical Center Groningen
More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: KineMed
ClinicalTrials.gov Identifier: NCT00476710     History of Changes
Other Study ID Numbers: KM-11B
First Posted: May 22, 2007    Key Record Dates
Last Update Posted: April 1, 2015
Last Verified: March 2015

Keywords provided by KineMed:
Type 2 diabetes mellitus
Bile acid
Stable isotope
Colesevelam HCl
Impaired Glucose Tolerance

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Intolerance
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Colesevelam Hydrochloride
Bile Acids and Salts
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Gastrointestinal Agents