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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: colesevelam HCl
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Welchol then Placebo<br>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: colesevelam HCl<br>* 3.75 grams of colesevelam HCl (6 tablets)<br>* Other names: Welchol;Drug: placebo<br> <br> |
| Placebo Comparator: Placebo then Welchol<br>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: colesevelam HCl<br>* 3.75 grams of colesevelam HCl (6 tablets)<br>* Other names: Welchol;Drug: placebo<br> <br> |

What is the study measuring?
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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. |