Effects of Colesevelam HCl On Bile Acid Kinetics

This study has been completed.
Sponsor:
Collaborators:
Daiichi Sankyo Inc.
University Medical Centre Groningen
Diabetes & Glandular Disease Research Associates
Information provided by:
KineMed
ClinicalTrials.gov Identifier:
NCT00476710
First received: May 18, 2007
Last updated: May 5, 2009
Last verified: May 2009
  Purpose

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 Intervention
Type 2 Diabetes Mellitus
Impaired Glucose Tolerance
Drug: Colesevelam HCl

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by KineMed:

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

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

Estimated Enrollment: 36
Study Start Date: May 2007
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   40 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
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: NCT00476710

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

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00476710     History of Changes
Other Study ID Numbers: KM-11B
Study First Received: May 18, 2007
Last Updated: May 5, 2009
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

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
Hyperglycemia
Colesevelam
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014