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

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

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).

Study Overview

• Status: Unknown
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: vitamin A; Drug: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Tehran University of Medical Sciences, School of Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Investigators: Study Chair: Ali Akbar saboor Yaraghi, PhD, Tehran University Of Medical Sciences; Principal Investigator: Maryam Mahmoudi, MD, PhD student, Tehran University of Medical Siences; Study Chair: Fereidon Siassi, PhD, Tehran University Of Medical Sciences

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Anticipated): March 1, 2013

Study Registration Dates

• First Submitted: August 20, 2009
• First Submitted That Met QC Criteria: August 20, 2009
• First Posted (Estimate): August 21, 2009

Study Record Updates

• Last Update Posted (Estimate): June 5, 2012
• Last Update Submitted That Met QC Criteria: June 2, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Atherosclerosis; Vitamin A; CD4-Positive T-Lymphocytes; Th1 Cells; Th2 Cells
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin A
• Other Study ID Numbers: 86-04-27-6617