The Study of the Effects of Vitamin A on Immune System in Patients With Atherosclerosis

Study Overview
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Brief Summary
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The aim of this study is the comparison between the effects of supplementation with 25000 IU preformed vitamin A (retinyl palmitate) or placebo for 3 months on immune system and Th1/Th2 balance in patients with and without atherosclerosis (documented with angiography).

Detailed Description
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Atherosclerosis, the leading cause of death and disability in the world, is considered an inflammatory disease with a complex etiology. The immune system has a prominent role in the formation, development and destabilization of atherosclerotic plaques. A whole range of identified cytokines have been shown to play a part in atherogenesis, some with proatherogenic properties while others having antiatherogenic properties. With increasing evidence for the significant role of inflammation and the cytokines involved together with the Th1/Th2 imbalance in atherosclerosis and its progression to Coronary artery diseases (CADs), the control of cytokine production may become potential therapeutic targets and modulation of the Th1/Th2 balance may provide a new pharmacological tool to treat this disease. Vitamin A (VA) or VA-like analogs known as retinoids, are potent hormonal modifiers of type 1 or type 2 responses but a definitive description of their mechanism(s) of action is lacking. high level dietary vitamin A enhances Th2 cytokine production and IgA responses, and is likely to decrease Th1 cytokine production. Retinoic acid inhibits IL 12 production in activated macrophages, and RA pretreatment of macrophages reduces IFNγ production and increases IL4 production in antigen primed CD4 T cells. Supplemental treatment with vitamin A or retinoic acid (RA) decreases IFNγ and increases IL5, IL10, and IL4 production. Thus, vitamin A deficiency biases the immune response in a Th1 direction, whereas high level dietary vitamin A may bias the response in a Th2 direction.

Official Title
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The Study of the Effects of Vitamin A Supplementation on Immune System and Th1/Th2 Balance in Patients With Atherosclerosis

Conditions
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Atherosclerosis

Intervention / Treatment
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* Drug: vitamin A
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The criteria for enrollment of the patients and control subjects is consecutive patients of both sexes referred to the Division of Cardiology of the one of the Hospitals of Tehran University of Medical Sciences for coronary angiography for investigation of chest pain and/or suspected CAD. Exclusion Criteria: Patients who have diseases which affect on Th1/Th2 balance such as asthma, active viral infections, and autoimmune diseases, OR Patients who have allergy to vitamin A compounds, OR Patients who have used vitamin supplements in last 3 months.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 60 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: with atherosclerosis/ vitamin A<br>patients with angiographically confirmed CAD (defined as luminal stenosis ≥50% in at least one major coronary artery branch)who receive 25000 IU/day vitamin A | Drug: vitamin A<br>* 1 cap vitamin A 25000 IU/day for 3 month<br>|
| Placebo Comparator: with atherosclerosis/ placebo<br>patients with angiographically confirmed CAD (defined as luminal stenosis ≥50% in at least one major coronary artery branch)who receive placebo | Drug: placebo<br>* 1 cap placebo/day for 3 month<br>|
| Active Comparator: without atherosclerosis/ vitamin A<br>patients in whom significant (e.g. stenosis ≥ 50%) CAD is ruled out by coronary angiography, who receive 2500 Iu/day vitamin A | Drug: vitamin A<br>* 1 cap vitamin A 25000 IU/day for 3 month<br>|
| Placebo Comparator: without athrosclerosis/ placebo<br>patients in whom significant (e.g. stenosis ≥ 50%) CAD is ruled out by coronary angiography, who receive placebo | Drug: placebo<br>* 1 cap placebo/day for 3 month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum levels of IL4, IL10, IFN γ, IL2, IL12 |  | first day and after 3 month | 
| PBMC supernatant levels of IL4, IL10, IFN γ, IL2, IL12 |  | first day and after 3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum Total cholesterol |  | first day and after 3 month | 
| serum HDL cholesterol |  | first day and after 3 month | 
| serum triglycerides level |  | first day and after 3 month | 
| serum Apo A, Apo B and CRP levels |  | first day and after 3 month | 
| serum oxLDL |  | first day and after 3 month | 
| RBP/ TTR ratio |  | first day and after 3 month | 
| lymphocyte proliferation assay (MTT) |  | first day and after 3 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atherosclerosis, Coronary Artery Disease, Vitamin A, CD4-Positive T-Lymphocytes, Th1 Cells, Th2 Cells