Effects of Exenatide on Glycemic Control and Weight in Continuous Subcutaneous Insulin Infusion (CSII) Type 2 Treated Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to determine whether exenatide is effective to improve glycemic control among type 2 diabetic patients treated by insulin pump therapy.

Official Title
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Effects of EXEnatide on Glycemic Control and Weight Over 26 Weeks in Continuous Subcutaneous Insulin Infusion (CSII) Treated Patients With Type 2 Diabetes : a Phase 2/3 Double Blind randoMized Placebo-controlled Trial.

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Exenatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women aged 35 to 70 Type 2 diabetes diagnosed for at least 12 months, according the criteria of the American Diabetes Association : presence of classic symptoms of diabetes mellitus with unequivocal elevation of plasma glucose (2-hour post-prandial or random glucose >200 mg/dL) or fasting plasma glucose elevation on more than 1 occasion > 125 mg/dL or patient currently undergoing pharmacological and/or non-pharmacological treatment for diabetes mellitus CSII treatment using a rapid analog for at least 6 month (CSII being initiated in patients with HbA1c > 8 % despite a well-conducted MDI trial using a 2 to 5 daily injection regimen) HbA1c ≥ 7,5% and ≤ 10 % BMI ≥ 25 and ≤ 45 Stable body weight (≤10% variation) during the 3 last months Exclusion Criteria: Type 1 diabetes assessed by positive anti-GAD65 or anti-insulin or anti-IA2 antibodies Monogenic diabetes (MODY, mitochondrial diabetes…) Current treatment with OHA (OHA ought to be interrupted at least two months prior to inclusion in the study) Current treatment specifically addressed for weight lost (orlistat, sibutramine, rimonabant may be interrupted at least 3 months prior to inclusion in the study) Use of corticosteroid therapy for more than 10 days within the 3-past months, or patient who ought to be treated by corticosteroid during the study period Clinically significant hepatic disease Documented gastroparesis, or current use of drugs that directly affect gastrointestinal motility, or any significant abdominal disease that may increase the risk of adverse gastrointestinal effects induced by exenatide Kidney failure (MDRD less than 50 ml/min) Pregnancy/breastfeeding Any social and/or mental condition rendering the subject unable to understand the scope and possible consequences of the study Concurrent enrolment in another clinical trial Geographically inaccessible for follow-up visits required by protocol

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: exenatide<br>55 subjects | Drug: Exenatide<br>* Research drug (exenatide or placebo), will begin at V0, after randomization. The initial dosage for the first month will be 5 µg SC BID. Injections can be administered at any time within the 60 minute period before the morning and evening meal. From V1, research drug will be titrated from 5 to 10 µg SC BID. If gastro-intestinal adverse effects occur with 10 µg SC BID, the dosage will be back-titrated to 5 µg SC BID. Thus, the higher research drug dosage tolerated will be used during the study time.<br>* Other names: Exenatide = BYETTA (R);|
| Placebo Comparator: Placebo<br>55 subjects | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to 6 months of centrally measured HbA1c |  | baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in weight, BMI, waist circumference, 6 points glucose profile, insulin doses, % of daily use of insulin as basal rate, % of daily use of insulin as bolus, quality of life questionnaire |  | baseline to 6 months | 
| Change from baseline in mean blood glucose value | occurrence of hyperglycemia above 190 mg/dl expressed as Area under the Curve (high) above 190 mg/dl (10.5 mmol/l), occurrence of hypoglycemia below 70 mg/dl (3.9 mmol/l) expressed as Area Under the Curve (low) below 70 mg/dl, glycemic variability (MAGE index). | baseline to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes, CSII, Exenatide, Double Blind Placebo Controlled Study