Effects of Colesevelam on How the Body Responds to Insulin in Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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This study is designed to assess the potential mechanism of action by which WelChol® (colesevelam) may improve blood glucose control in patients with type 2 diabetes

Official Title
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Effects of Colesevelam on Insulin Sensitivity in Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Colesevelam
* Drug: Colesevelam matching placebo
* Drug: Insulin glargine (Lantus)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between the ages of 18 - 75, inclusive Diagnosed with type 2 diabetes Hemoglobin A1c value greater than or equal to 8.0% Antidiabetic treatments may include sulfonylurea agents (non-sulfonylurea agents must be withdrawn) Overweight, obese (body mass index 25-45 kg/m2) Exclusion Criteria: Change of dose of lipid or blood pressure lowering therapy within past three months Previous treatment with colesevelam for hyperlipidemia Serum triglyceride greater than 500 mg/dL Serum low density lipoprotein-cholesterol less than 60 mg/dL

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>colesevelam 3.8g administered daily for 12 weeks | Drug: Colesevelam<br>* Colesevelam 3.8g for 12 weeks<br>|
| Placebo Comparator: 2<br>Colesevelam matching placebo for 12 weeks | Drug: Colesevelam matching placebo<br>* Colesevelam matching placebo for 12 weeks<br>|
| Active Comparator: 3<br>open-label Insulin Glargine for 12 weeks | Drug: Insulin glargine (Lantus)<br>* Insulin glargine for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Endogenous (Hepatic) Glucose Output During a High-dose Insulin Infusion From Baseline to After 12 Weeks of Treatment. | The parameter measured is the endogenous (hepatic) glucose output during a high-dose insulin infusion. A decrease after treatment with colesevelam is indicative of greater sensitivity of the liver to insulin. | Baseline to 12 weeks | 
| Difference in Endogenous (Hepatic) Glucose Output During a Low-dose Insulin Infusion From Baseline to Week 12. | The parameter measured is the endogenous (hepatic) glucose output during a low-dose insulin infusion. A decrease is indicative of greater senstitivity of the liver to insulin. | Baseline to 12 weeks | 
| Acute Effect of a Single Dose of Colesevelam on Oral Glucose Absorption From Baseline to First Dose | Change in area under the curve for glucose (AUCg) after a glucose tolerance test. A decrease in AUCg is indicative of a drug effect. | Baseline (Day -4) to first dose (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Acute Effect of Colesevelam (Multiple Doses) on Oral Glucose Absorption From Baseline to 12 Weeks | The parameter measured is the change in area under the curve for glucose(AUCg) after an oral glucose tolerance test. A decrease in AUCg indicative of drug effect on glucose absorption. | Baseline to 12 weeks | 
| Change in Hemoglobin A1C Due to Effect of Colesevelam From Baseline to 12 Weeks | The parameter measured is the percent of hemoglobin A that is glycosylated. A decrease in this parameter is indicative of improved glucose control. | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mechanism of action insulin sensitivity