The Effect of Welchol on Glucose Metabolism in Type 2 Diabetics

NCT00951899 | Completed Phase 4 Results DMC

• 4 other identifiers: 08-008284R01DK078646R01DK082396UL1RR024150
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study was to determine the metabolic mechanism for a certain type medication's ability to lower blood sugar after a meal in Type 2 Diabetics, in order to develop a better understanding of it's potential role in the treatment of obesity.

Conditions

Type 2 Diabetes

Keywords

Incretins; colesevelam; hepatobiliary circulation

Outcome Measures

Primary Outcomes (1)

• Total Disposition Index

  Total Disposition Index (DI) is a calculated value which represents the ability of a person's pancreas to lower blood glucose. A higher number means the pancreas is better able to lower blood glucose and a lower number means the pancreas is less able to lower blood glucose.

  Baseline, 12 weeks

Secondary Outcomes (8)

• Total Fasting Glucagon-Like Peptide-1 (GLP-1) Concentration

  Baseline, 12 weeks

• Plasma Glucose Concentration

  Baseline, 12 Weeks

• Glycosylated Hemoglobin (HbA1c)

  Baseline, 12 weeks

• Insulin Concentration

  Baseline, 12 Weeks

• Fasting Endogenous Glucose Production (EGP)

  Baseline, 12 Weeks

Study Arms (2)

Colesevelam

EXPERIMENTAL

Treatment with colesevelam hydrochloride in addition to Metformin and Diet

Drug: Colesevelam; Behavioral: Diet; Drug: Metformin

Placebo

PLACEBO COMPARATOR

Treatment with placebo in addition to Metformin and Diet

Other: Placebo; Behavioral: Diet; Drug: Metformin

Interventions

Colesevelam DRUG

Colesevelam hydrochloride; three 625mg tablets taken orally twice per day before breakfast and before the evening meal over a 12-week treatment period.

Also known as: Welchol

Colesevelam

Placebo OTHER

Three placebo tablets matching the active drug colesevelam in appearance, taken orally twice per day before breakfast and before the evening meal over a 12-week treatment period.

Placebo

Diet BEHAVIORAL

Subjects were instructed to follow a weight maintenance diet (\~55% carbohydrate, 30% fat and 15% protein) for the 12 week study period.

Colesevelam; Placebo

Metformin DRUG

Subjects continued to take their pre-study therapeutic doses of metformin (Metformin 500mg tablets taken by mouth twice daily for a total daily dose of 1000 to 2000 mg) through the 12 week study period.

Also known as: Glucophage, Glucophage XR, Glumetza, Fortamet

Colesevelam; Placebo

Eligibility Criteria

• Age: 35 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 35-70 years old.
• Body Mass Index greater than 19kg/m\^2 or less than 40kg/m\^2 or a total weight less than 130 kilograms.
• Negative pregnancy test for women of childbearing potential.
• Absence of gastrointestinal symptoms.
• Signed informed consent.
• Treatment with diet and/or metformin. Subjects must be on stable therapeutic doses of metformin and/or lipid-lowering agents for more than 3 months.

You may not qualify if:

• Structural or metabolic diseases/conditions that affect the gastrointestinal system, or functional gastrointestinal disorders. A screening Bowel Disease Questionnaire will be used to exclude subjects with irritable bowel syndrome. Patients with a history of dysphagia or intestinal motility disorders will be excluded.
• Prior history of pancreatitis.
• Prior history of hypertriglyceridemia (500mg/dL or greater).
• Currently using a bile-acid binding resin such as colesevelam, colestipol, colestimide or cholestyramine.
• To ensure homogeneity between treatment groups we will exclude subjects with insulin-treated type 2 diabetes mellitus, subjects who have received an inhibitors of dipeptidyl peptidase 4 (DPP-4 inhibitors) or "gliptins" (a class of oral hypoglycemics), Byetta or sulfonylurea agent in the past three months.
• HbA1c greater than 9.0%.
• Patients who have not been stable on all medications for a period exceeding 3 months.
• Use of drugs or agents within the past 2 weeks or planned use in the subsequent 4 weeks during the study period that:
• Alter GI transit including laxatives, magnesium or aluminum-containing antacids, prokinetics, erythromycin, narcotics, anticholinergics, tricyclic antidepressants, Selective Serotonin Reuptake Inhibitors (SSRIs) and newer antidepressants.
• Opiate-based analgesic drugs (Note: intermittent or chronic use of aspirin or non-steroidal anti-inflammatory drugs (NSAID) will be allowed).
• Antihistamines
• Anticholinergic agents
• Female subjects who are pregnant or breast-feeding. Females must be either surgically sterilized, postmenopausal (\>12 months since last menses), or, if of childbearing potential, using reliable methods of contraception as determined by the physician.
• Clinical evidence (including physical exam and Electrocardiogram) of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric, or other disease that interfere with the objectives of the study. Any candidate participants with such disorders mentioned will be referred to their general physician.

Sponsors & Collaborators

• Mayo Clinic: lead
• Daiichi Sankyo: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Smushkin G, Sathananthan M, Piccinini F, Dalla Man C, Law JH, Cobelli C, Zinsmeister AR, Rizza RA, Vella A. The effect of a bile acid sequestrant on glucose metabolism in subjects with type 2 diabetes. Diabetes. 2013 Apr;62(4):1094-101. doi: 10.2337/db12-0923. Epub 2012 Dec 18.

  PMID: 23250357 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Colesevelam Hydrochloride; Diet; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Allylamine; Amines; Organic Chemicals; Allyl Compounds; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Biguanides; Guanidines; Amidines

Results Point of Contact

• Title: Dr. Adrian Vella
• Organization: Mayo Clinic

vella.adrian@mayo.edu

507-284-3289

Study Officials

• Adrian Vella, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor of Medicine, Endocrinology

Study Record Dates

• First Submitted: July 31, 2009
• First Posted: August 4, 2009
• Study Start: August 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: December 1, 2012
• Last Updated: November 11, 2013
• Results First Posted: August 15, 2013

Record last verified: 2013-10

Locations

US (1)