Effects of Colesevelam HCl On Bile Acid Kinetics

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00476710
• Other study ID #: KM-11B
• Status: Completed
• Phase: N/A
• First received: May 18, 2007
• Last updated: March 30, 2015
• Start date: May 2007
• Est. completion date: April 2009

Study information

• Verified date: March 2015
• Source: KineMed
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 40 Years to 60 Years

Eligibility

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 Design

Observational Model: Case Control, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Glucose Intolerance
• Impaired Glucose Tolerance
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Colesevelam HCl

Locations

Country	Name	City	State
United States	Diabetes & Glandular Disease Research Associates, Inc.	San Antonio	Texas

Sponsors (4)

Lead Sponsor	Collaborator
KineMed	Daiichi Sankyo Inc., Diabetes & Glandular Disease Research Associates, University Medical Center Groningen

Country where clinical trial is conducted

United States, 

References & Publications (7)

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

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

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

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. — View Citation

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. — View Citation

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. — View Citation

Zieve FJ, Kalin MF, Schwartz SL, Jones MR, Bailey WL. Results of the glucose-lowering effect of WelChol study (GLOWS): a randomized, double-blind, placebo-controlled pilot study evaluating the effect of colesevelam hydrochloride on glycemic control in subjects with type 2 diabetes. Clin Ther. 2007 Jan;29(1):74-83. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bile Acid Pool Size and Kinetic Parameters		60 days of treatment	No
Secondary	Resting Metabolic Rate		60 days of treatment	No

External Links

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