Effects of Colesevelam HCl On Bile Acid Kinetics

March 30, 2015 updated by: KineMed

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

36

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • San Antonio, Texas, United States, 78229
        • Diabetes & Glandular Disease Research Associates, Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

overweight and obese people with normal glucose metabolism, impaired glucose tolerance and frank type 2 diabetes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Bile Acid Pool Size and Kinetic Parameters
Time Frame: 60 days of treatment
60 days of treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Resting Metabolic Rate
Time Frame: 60 days of treatment
60 days of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

KineMed

Collaborators

University Medical Center Groningen
Daiichi Sankyo, Inc.
Diabetes & Glandular Disease Research Associates

Investigators

  • Principal Investigator: Elizabeth J Murphy, MD, KineMed, Inc.
  • Principal Investigator: Folkert Kuipers, PhD, University Medical Center Groningen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

May 18, 2007

First Submitted That Met QC Criteria

May 18, 2007

First Posted (Estimate)

May 22, 2007

Study Record Updates

Last Update Posted (Estimate)

April 1, 2015

Last Update Submitted That Met QC Criteria

March 30, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KM-11B

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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