An Intervention Trial for Cardiac Neuropathy in Type 1 Diabetes

Study Overview
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Brief Summary
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The focus of this project is cardiovascular diabetic autonomic neuropathy (DAN). DAN affects the nerves that control heart rate and blood flow to the heart in people with diabetes. DAN may cause problems with the rhythm of the heartbeat or decrease blood flow to the heart. Three medications will be tested for their effectiveness in DAN.

Official Title
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Oxidative Stress and Cardiovascular Denervation in Diabetes: An Interventional Trial

Conditions
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Diabetic Autonomic Neuropathy

Intervention / Treatment
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* Drug: ORAL ANTIOXIDANT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes A1C <9% Mild neuropathy Mild retinopathy Mild nephropathy Exclusion Criteria: History of drug or alcohol dependence, heart disease, viral illness, liver disease, advanced kidney disease Pregnant or nursing Severely overweight

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: ORAL ANTIOXIDANT<br>Allopurinol (300mg daily), ALA (600mg twice daily) nicotinamide (750 mg twice daily) Given orally These drugs were given together as a combination and not as individual treatment. | Drug: ORAL ANTIOXIDANT<br>* Comparison of triple antioxidant combination therapy vs placebo.<br>* Other names: nicotinamide (750 mg twice daily);|
| Placebo Comparator: Placebo<br>Placebo administered twice daily. | Drug: ORAL ANTIOXIDANT<br>* Comparison of triple antioxidant combination therapy vs placebo.<br>* Other names: nicotinamide (750 mg twice daily);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global [11C]HED Retention Index (RI) | Distal defects in [11C]meta-hydroxyephedrine ([11C]HED) retention involving at least 10 % of the left ventricle was used to define Cardiac Autonomic Neuropathy (CAN). The retention index (RI) is the unit of measure and is expressed as [11C]HEDblood min -1[ml tissue]-1 PET Data of Randomized Subjects at Baseline and 24-Months The primary outcome was the change in the global [11C]HED RI = measure of cardiac innervation at 24 months in participants taking the active drug compared with those on placebo. | Baseline, 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Coronary Flow Reserve as a Measure of Endothelial Function | global myocardial blood flow reserve as a measure of endothelial function. Measured by PET using [13N]ammonia at rest and during adenosine stimulated coronary vasodilation. | Baseline, 24 months | 
| Systemic Oxidative Stress | ng of 8-epi prostaglandin F2alpha /G creatinine assessed in 24 hour urine collection | 24 months | 
| Inflammation | High Sensitivity CRP (nmol/L) | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes, Oxidative Stress, Diabetic Complications, Neuropathy