The Effect of Welchol on Glucose Metabolism in Type 2 Diabetics

NCT ID: NCT00951899

Last Updated: 2013-11-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2012-12-31

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.

Detailed Description

Welchol (colesevelam hydrochloride) is a bile acid sequestrant (BAS) recently approved by the FDA for glucose lowering in patients with type 2 diabetes mellitus. Four randomized, controlled clinical studies in subjects with type 2 diabetes have demonstrated significant treatment difference in HbA1c (-0.5%). Study durations ranged from 12-26 weeks of therapy. In diabetes clinical studies, a therapeutic response to colesevelam hydrochloride, as reflected by reduction in A1c was initially noted following 4-6 weeks of treatment and reached maximal or near-maximal effect after 12-18 weeks of treatment. Reductions in both fasting plasma glucose and postprandial concentrations have been demonstrated. Simple measures of insulin secretion and action have suggested that this is due to improved insulin action rather than improved insulin secretion. The mechanism by which bile acids interact with the key pathways regulating glucose concentrations is largely unknown. The investigators propose a randomized, double-blind, placebo controlled trial with a parallel-group design where subjects are randomized to receive colesevelam or matching placebo for a 12 week treatment period. A labeled mixed meal before and after treatment will be used to measure intestinal transit, postprandial and fasting glucose fluxes, insulin secretion and action as well as enteroendocrine secretion.

Conditions

Type 2 Diabetes

Keywords

Incretins; colesevelam; hepatobiliary circulation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Colesevelam

Treatment with colesevelam hydrochloride in addition to Metformin and Diet

Group Type: EXPERIMENTAL

Colesevelam

Intervention Type: DRUG

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

Diet

Intervention Type: BEHAVIORAL

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

Metformin

Intervention Type: 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.

Placebo

Treatment with placebo in addition to Metformin and Diet

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Diet

Intervention Type: BEHAVIORAL

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

Metformin

Intervention Type: 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.

Interventions

Colesevelam

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

Intervention Type: DRUG

Placebo

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.

Intervention Type: OTHER

Diet

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

Intervention Type: BEHAVIORAL

Metformin

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.

Intervention Type: DRUG

Other Intervention Names

Welchol; Glucophage; Glucophage XR; Glumetza; Fortamet

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Adrian Vella

MD, Professor of Medicine, Endocrinology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adrian Vella, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 23250357 (View on PubMed)

Other Identifiers

R01DK078646

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01DK082396

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UL1RR024150

Identifier Type: NIH

Identifier Source: secondary_id

View Link

08-008284

Identifier Type: -

Identifier Source: org_study_id