Effects of Colesevelam HCl On Bile Acid Kinetics - Full Text View

Sponsors and Collaborators:	KineMed Daiichi Sankyo Inc. University Medical Centre Groningen Diabetes & Glandular Disease Research Associates
Information provided by:	KineMed
ClinicalTrials.gov Identifier:	NCT00476710

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

MedlinePlus related topics: Diabetes

Drug Information available for: Dextrose Colesevelam GT31-104

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Pharmacodynamics Study
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

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
Estimated Study Completion Date:	December 2007

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00476710

Locations

United States, Texas
Diabetes & Glandular Disease Research Associates, Inc.	Recruiting
San Antonio, Texas, United States, 78229
Contact: Bruce Slade 210-615-5565 bslade@dgdresearch.com
Principal Investigator: Sherwyn L Schwartz, MD

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

Related Info This link exits the ClinicalTrials.gov site

Publications:

Grundy SM, Ahrens EH Jr, Salen G. Interruption of the enterohepatic circulation of bile acids in man: comparative effects of cholestyramine and ileal exclusion on cholesterol metabolism. J Lab Clin Med. 1971 Jul;78(1):94-121. No abstract available.

Shepherd J, Packard CJ, Bicker S, Lawrie TD, Morgan HG. Cholestyramine promotes receptor-mediated low-density-lipoprotein catabolism. N Engl J Med. 1980 May 29;302(22):1219-22.

Abrams JJ, Ginsberg H, Grundy SM. Metabolism of cholesterol and plasma triglycerides in nonketotic diabetes mellitus. Diabetes. 1982 Oct;31(10):903-10.

Andersen E, Karlaganis G, Sjovall J. Altered bile acid profiles in duodenal bile and urine in diabetic subjects. Eur J Clin Invest. 1988 Apr;18(2):166-72.

Bennion LJ, Grundy SM. Effects of diabetes mellitus on cholesterol metabolism in man. N Engl J Med. 1977 Jun 16;296(24):1365-71.

Hulzebos CV, Renfurm L, Bandsma RH, Verkade HJ, Boer T, Boverhof R, Tanaka H, Mierau I, Sauer PJ, Kuipers F, Stellaard F. Measurement of parameters of cholic acid kinetics in plasma using a microscale stable isotope dilution technique: application to rodents and humans. J Lipid Res. 2001 Nov;42(11):1923-9.

Study ID Numbers:	KM-11B
Study First Received:	May 18, 2007
Last Updated:	May 18, 2007
ClinicalTrials.gov Identifier:	NCT00476710
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

Study placed in the following topic categories:

Colesevelam
Hyperglycemia
Metabolic Diseases
Glucose Intolerance
Diabetes Mellitus, Type 2

Diabetes Mellitus
Endocrine System Diseases
Endocrinopathy
Metabolic disorder
Glucose Metabolism Disorders

Additional relevant MeSH terms:

Antimetabolites
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses

Antilipemic Agents
Anticholesteremic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009