NCT00476710

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
36

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started May 2007

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2007

Completed
17 days until next milestone

First Submitted

Initial submission to the registry

May 18, 2007

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 22, 2007

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2009

Completed
Last Updated

April 1, 2015

Status Verified

March 1, 2015

Enrollment Period

1.9 years

First QC Date

May 18, 2007

Last Update Submit

March 30, 2015

Conditions

Type 2 Diabetes MellitusImpaired Glucose Tolerance

Keywords

Type 2 diabetes mellitusBile acidStable isotopeColesevelam HClImpaired Glucose Tolerance

Outcome Measures

Primary Outcomes (1)

  • Bile Acid Pool Size and Kinetic Parameters

    60 days of treatment

Secondary Outcomes (1)

  • Resting Metabolic Rate

    60 days of treatment

Study Arms (3)

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

Interventions

Colesevelam HClDRUG
Frank type 2 diabetesImpaired Glucose ToleranceNormal Glucose Metabolism

Eligibility Criteria

Age40 Years - 60 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)
Sampling MethodProbability Sample
Study Population

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

You may qualify if:

  • 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
  • hr OGTT glucose \< 140 mg/dL
  • fasting glucose \< 100 mg/dL
  • TG \< 150 mg/dL
  • HDL cholesterol \>= 40 mg/dL
  • Impaired Glucose Tolerance Subjects
  • hr OGTT glucose \>= 140 and \< 200 mg/dL

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Diabetes & Glandular Disease Research Associates, Inc.

San Antonio, Texas, 78229, United States

Location

Related Publications (8)

  • 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.

    PMID: 5569253BACKGROUND

  • 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. doi: 10.1056/NEJM198005293022202.

    PMID: 7366673BACKGROUND

  • 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. doi: 10.1016/j.clinthera.2007.01.003.

    PMID: 17379048BACKGROUND

  • Abrams JJ, Ginsberg H, Grundy SM. Metabolism of cholesterol and plasma triglycerides in nonketotic diabetes mellitus. Diabetes. 1982 Oct;31(10):903-10. doi: 10.2337/diab.31.10.903.

    PMID: 6759223BACKGROUND

  • 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. doi: 10.1111/j.1365-2362.1988.tb02408.x.

    PMID: 3133222BACKGROUND

  • Bennion LJ, Grundy SM. Effects of diabetes mellitus on cholesterol metabolism in man. N Engl J Med. 1977 Jun 16;296(24):1365-71. doi: 10.1056/NEJM197706162962401.

    PMID: 870827BACKGROUND

  • 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.

    PMID: 11714862BACKGROUND

  • Brufau G, Stellaard F, Prado K, Bloks VW, Jonkers E, Boverhof R, Kuipers F, Murphy EJ. Improved glycemic control with colesevelam treatment in patients with type 2 diabetes is not directly associated with changes in bile acid metabolism. Hepatology. 2010 Oct;52(4):1455-64. doi: 10.1002/hep.23831.

    PMID: 20725912DERIVED

Related Links

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Glucose Intolerance

Interventions

Colesevelam Hydrochloride

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesHyperglycemia

Intervention Hierarchy (Ancestors)

AllylamineAminesOrganic ChemicalsAllyl CompoundsAlkenesHydrocarbons, AcyclicHydrocarbons

Study Officials

  • Elizabeth J Murphy, MD

    KineMed, Inc.

    PRINCIPAL INVESTIGATOR

  • Folkert Kuipers, PhD

    University Medical Center Groningen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
RETROSPECTIVE
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 18, 2007

First Posted

May 22, 2007

Study Start

May 1, 2007

Primary Completion

April 1, 2009

Study Completion

April 1, 2009

Last Updated

April 1, 2015

Record last verified: 2015-03

Locations

US(1)