Glycemic Effect of Colesevelam HCl (Welchol) in Patients With Type 2 Diabetes

Use of Continuous Glucose Monitoring With Ambulatory Glucose Profile Analysis to Demonstrate the Glycemic Effect of Colesevelam HCl (Welchol) in Patients With Type 2 Diabetes

The purpose of this study is to obtain continuous glucose monitoring (CGM) data from individuals taking Welchol compared to placebo. The CGM data will determine the effect on glucose control of adding Welchol to an anti-diabetic medication regimen.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: placebo; Drug: colesevelam HCl

Detailed Description

To understand the effect of the addition of colesevelam HCl to oral agent therapy in individuals with type 2 diabetes on glycemic control by utilizing a novel technology, continuous glucose monitoring with ambulatory glucose profile analysis. To date there are no studies of this compound that have employed continuous glucose monitoring (CGM) with ambulatory glucose profile (AGP) analysis to obtain data that will detail the diurnal glucose patterns associated with this therapy. We plan to employ CGM at critical points throughout the study. AGP analysis will enable rapid assessment of the clinical status of the subject. Using statistically stable estimates of hourly values represented by five percentile curves AGP depicts glucose exposure, variability and stability. Previously, we have used AGP analysis to characterize glucose perturbations in individuals ranging from normal glucose tolerance to overt type 2 diabetes.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • International Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects ≥18 and ≤75 years of age
• Clinical diagnosis of type 2 diabetes
• Currently treated with metformin, a sulfonylurea, or combination metformin/sulfonylurea; stable dose for ≥3 months
• HbA1c of 7.0-9.0% inclusive
• If taking lipid lowering medications, stable dose for >30 days

Exclusion Criteria:

• Taken oral or injected prednisone or cortisone medications in the previous 30 days. (Topical or inhaled steroids will not be considered excluded medications.)
• Current use of insulin or TZD's, or incretins
• LDL <70 mg/dL
• Serum triglycerides >500 mg/dL
• History of hypertriglyceridemia-induced pancreatitis
• History of gastrointestinal disorder such as dysphagia, swallowing disorder, intestinal motility disorder or prior bowel obstruction
• History or presence of any severe medical or psychological condition or chronic conditions/infections that in the opinion of the Investigator would compromise the subject's safety or successful participation in the study
• Unable to follow the study protocol
• Unable to speak, read and write in English
• Pregnant, planning to become pregnant, breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Welchol then Placebo; 3.75 grams of colesevelam HCl (Welchol) at evening meal for 12 weeks, and then crossover to placebo at evening meal for 12 weeks.	Drug: placebo; Drug: colesevelam HCl; 3.75 grams of colesevelam HCl (6 tablets); Other Names: Welchol
Placebo Comparator: Placebo then Welchol; Placebo taken for 12 weeks at evening meal, and then crossover to 3.75 grams of colesevelam HCl taken at evening meal fro 12 weeks.	Drug: placebo; Drug: colesevelam HCl; 3.75 grams of colesevelam HCl (6 tablets); Other Names: Welchol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Norm AUC Average by Group (Normalized)	Double Blinded CGM used for 2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.	2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.
Sleep Norm AUC Average by Group (Normalized)	Overnight glucose captured by CGM.	2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.
Wake Norm AUC Average by Group (Normalized)	Wake glucose captured by continuous glucose monitoring (CGM).	2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.
Hypoglycemia Percentage of Time <70 mg/dL Average by Group	Ambulatory glucose profile (AGP) reports were examined for the changes in the incidence of hypoglycemia (CGM<70 mg/dL)	2 week periods at the start of treatment 1, end of treatment 1, start of treatment 2, and end of treatment 2.

Collaborators and Investigators

• Sponsor: HealthPartners Institute
• Collaborators: Daiichi Sankyo, Inc.; International Diabetes Center at Park Nicollet
• Investigators: Principal Investigator: Robert M. Cuddihy, MD, International Diabetes Center at Park Nicollet; Study Director: Roger S. Mazze, PhD, International Diabetes Center at Park Nicollet; Principal Investigator: Elinor S. Strock, APRN, BC, International Diabetes Center at Park Nicollet

Publications and helpful links

General Publications

• Bays HE, Goldberg RB, Truitt KE, Jones MR. Colesevelam hydrochloride therapy in patients with type 2 diabetes mellitus treated with metformin: glucose and lipid effects. Arch Intern Med. 2008 Oct 13;168(18):1975-83. doi: 10.1001/archinte.168.18.1975.
• Mazze RS, Strock E, Wesley D, Borgman S, Morgan B, Bergenstal R, Cuddihy R. Characterizing glucose exposure for individuals with normal glucose tolerance using continuous glucose monitoring and ambulatory glucose profile analysis. Diabetes Technol Ther. 2008 Jun;10(3):149-59. doi: 10.1089/dia.2007.0293.
• Goldberg RB, Fonseca VA, Truitt KE, Jones MR. Efficacy and safety of colesevelam in patients with type 2 diabetes mellitus and inadequate glycemic control receiving insulin-based therapy. Arch Intern Med. 2008 Jul 28;168(14):1531-40. doi: 10.1001/archinte.168.14.1531.
• Mazze RS, Strock E, Borgman S, Wesley D, Stout P, Racchini J. Evaluating the accuracy, reliability, and clinical applicability of continuous glucose monitoring (CGM): Is CGM ready for real time? Diabetes Technol Ther. 2009 Jan;11(1):11-8. doi: 10.1089/dia.2008.0041.
• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: October 12, 2009
• First Submitted That Met QC Criteria: October 13, 2009
• First Posted (Estimate): October 14, 2009

Study Record Updates

• Last Update Posted (Estimate): November 30, 2015
• Last Update Submitted That Met QC Criteria: November 25, 2015
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Colesevelam Hydrochloride
• Other Study ID Numbers: 03901-09-C