Evaluation of Exenatide in Patients With Diabetic Neuropathy

Study Overview
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Brief Summary
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This study will look at whether or not the medication exenatide improves signs and symptoms of diabetic peripheral neuropathy in people with type 2 diabetes and mild to moderate diabetic peripheral neuropathy.

Detailed Description
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This study will look at the effects of the medication exenatide on peripheral neuropathy in people with type 2 diabetes. Exenatide (trade name, BYETTA®) is an injectable medication used by people with type 2 diabetes to control blood sugar. Peripheral neuropathy is a complication of diabetes that can cause symptoms such as numbness, tingling or burning sensations in the feet and hands. Controlling blood sugars levels in type 2 diabetes is thought to prevent, delay or improve the damage to the nerve fibers that causes peripheral neuropathy. There is also some evidence that exenatide may have additional beneficial effects on the peripheral nerves, beyond the benefits of blood sugar control alone. In this study, about half of the participants will take exenatide by injection twice daily and the other half will take insulin glargine (Lantus®) by injection once daily. Both groups are expected to have similar improvement in blood sugar control. This study will show whether exenatide has beneficial effects on neuropathy beyond the benefits of better blood sugar control alone.

Official Title
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A Single-center,Proof of Concept,Randomized,Controlled Parallel Group Clinical Trial of the Effects of Exenatide vs. a Long Acting Insulin Analog to Evaluate the Efficacy of Exenatide in Patients With Diabetic Neuropathy and Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus, Diabetic Peripheral Neuropathy

Intervention / Treatment
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* Drug: Exenatide
* Drug: Glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes treated with one or more oral agents Persistent fasting glucose > 140 mg/dl or HbA1c > 7% Stable and maximally effective doses of one or more oral agents for 3 months Presence of diabetic peripheral neuropathy Age between 18 and 70 years No risk factors or other causes of neuropathy Willingness and capacity to sign the Institutional Review Board approved consent form and cooperate with the medical procedures for study duration Exclusion Criteria: Nursing mothers or pregnant women A history of previous kidney, pancreas or cardiac transplantation A past history of neuropathy (independent of diabetes) or with a disease known to be associated with neuropathy (e.g., hepatitis C, end stage renal disease, lupus) Amputation of any part of either lower extremity for any reason or traumatic loss of any part of either lower extremity or congenital absence or severe deformity of lower extremity HbA1c > 10% Participation in an experimental medication trial within 3 months of starting the study. Undergoing therapy for malignant disease other than basal- or squamous cell carcinoma Requiring long-term glucocorticoid therapy Inability or unwillingness to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide<br>Subjects will take exenatide by subcutaneous injection twice daily for 18 months | Drug: Exenatide<br>* Exenatide is given according to current FDA prescribing guidelines. Exenatide and other diabetes medications will be titrated in order to achieve optimal blood glucose levels<br>* Other names: Byetta;|
| Active Comparator: glargine<br>Subjects will take 1 daily injection of insulin glargine for 18 months. | Drug: Glargine<br>* Subjects will take 1 daily injection of insulin glargine in manner consistent with current prescribing guidelines. Glargine and other diabetes medications will be adjusted to achieve optimal levels of blood sugar control<br>* Other names: Lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed Clinical Neuropathy (CCN) | CCN was defined by a composite score comprised of at least two positive responses among symptoms, sensory signs, or absent or hypoactive reflexes consistent with a distal symmetrical polyneuropathy (16), and at least one abnormal nerve conduction study result in two anatomically distinct nerves, e.g. the sural sensory and peroneal motor nerves (defined as a amplitude < 5 μV and a conduction velocity < 40 m/sec for the sural nerve and an amplitude < 2.5 μV and a conduction velocity < 40 m/sec for the peroneal nerve). | 18 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac Autonomic Neuropathy (CAN) | Group differences in E/I ratio, a measure of cardiac autonomic function. | 18 months | 
| Cardiac Autonomic Neuropathy | resting heart rate as marker of autonomic function at rest | 18 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Neuropathy, Glucose, Control, Peripheral, Autonomic