Role of Alpha-lipoic Acid in Diabetes Melitus Type 1

Study Overview
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Brief Summary
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This study aims at investigating the possible effect of alpha-lipoic acid on endothelial dysfunction and atherosclerosis in children with type 1 diabetes mellitus.

Detailed Description
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Endothelial dysfunction and alterations in vascular structure are early indicators of future cardiovascular events. The atherosclerotic changes begin much earlier than the appearance of clinical disease. Endothelial dysfunction in diabetes may be the result of a combination of multiple stressors. In the patients with type 1 diabetes, a significant increase in the concentrations of endothelial markers was already observed at the early stages of the disease including vascular cell adhesion molecules (VCAM-1), intercellular adhesion molecules (sICAM-1), soluble E- selectin E (sE-Selektin), asymmetric dimethylarginine (ADMA), plasminogen activator inhibitor 1 (PAI-1) because their concentrations increase rapidly in states of cellular stress. Increased carotid intima-media thickness (CIMT) is a structural marker for early atherosclerosis that correlates with cardio-vascular risk factors. Alpha -lipoic acid supplementation may have role in Improving Endothelial Dysfunction and early Atherosclerosis due to its oxidative and anti-inflammatory effect.

Official Title
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The Possible Role of Alpha-Lipoic Acid in Improving Endothelial Dysfunction and Atherosclerosis in Children With Type 1 Diabetes Mellitus

Conditions
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Diabetes MellitusType 1

Intervention / Treatment
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* Other: Placebo
* Drug: Alpha Lipoic Acid 600 MG Oral Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with T1DM on insulin therapy ≥ 0.5 IU/kg/day. Age range between 12 and < 18 years old. Both sex. Duration of diabetes ≥ 3 years. Glycated hemoglobin of ≥ 7.5% Patients who are previously evaluated for endothelial dysfunction and atherosclerosis. Exclusion Criteria: Clinical evidence of heart failure, coronary artery disease, systemic hypertension, rheumatic fever, cardiomyopathy. Concurrent use of any medication other than insulin known to affect cardiac function (such as digitalis, angiotensin converting enzyme inhibitor, or β-blocker, etc…). Concurrent use of hyperlipidemia agents (Statin, fibrate). Concurrent use of antioxidants as selenium, vitamin C, vitamin E, etc.. Patients with inflammatory conditions. Patients with conditions predispose to oxidative stress (obesity, COPD, etc…). Patients with liver disease. Patients with thyroid disease. Patients with seizures.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 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 |
| --- | --- |
| Placebo Comparator: Placebo group who received insulin only plus placebo tablets<br>(Placebo group; n=22) which will receive insulin plus placebo tablets once daily for 6 months. | Other: Placebo<br>* Inactive capsules<br>|
| Active Comparator: ALA group who received Alpha lipoic acid plus insulin<br>(alpha-lipoic acid group; n=22) which will receive insulin plus ALA 600mg once daily for 6 months. | Drug: Alpha Lipoic Acid 600 MG Oral Capsule<br>* Universal antioxidant<br>* Other names: Thioctic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in carotid artery intima-media thickness (CIMT) | Measurement of carotid intima-media thickness (CIMT) which is mainly used to assess subclinical atherosclerosias and its assessment is based on ultrasound transducer | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in serum level of hs-CRP | High sensitivity C- reactive protein (hs-CRP) which will be assessed by ELISA. | Baseline and 6 months | 
| The change in serum level (MDA) | Malondialdehyde (MDA) which will be assessed by colorimetric method. | Baseline and 6 months | 
| The change in the serum level of VCAM-1 | Vascular cell adhesion molecule-1 (VCAM-1) a marker of endothelial dysfunction which will be assessed by ELISA. | Baseline and 6 months | 
| The change in the serum level of Apelin | Serum Apelin a marker of atherosclerosis which will be assessed by ELISA | Baseline and 6 months | 
| Lipid profile measuremt | Total cholesterol (TC), triglyceride (TG) and HDL-C will be assessed by enzymatic colorimetric method. | Baseline and 6 months | 
| Change in plasma level of (HbA1c %) | Glycated hemoglobin (HbA1c %) will be measured by ion exchange micro-column chromatographic method. | Baseline and 3,6 months | 
| Fast blood glucose measuremt | Fasting blood glucose will be determined by glucose oxidase method. | Baseline and 6 months |