EPA Supplementation on Vascular Inflammation, and Gene Expression of PON2 in Patients With Type II Diabetes Mellitus

Study Overview
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Brief Summary
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The aim of this study is to determining of the effects of Eicosapentaenoic acid (EPA) supplementation on serum activities of Paraoxonase-1 and Homocystein thiolactonase, and serum levels of some indicators of vascular inflammation, and the gene expression of PON2 in the peripheral blood mononuclear cell (PBMC) in the patients with type II diabetes mellitus.

Detailed Description
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The aim of this study is to determining of the effects of Eicosapentaenoic acid (EPA) supplementation on serum activities of Paraoxonase-1 and Homocystein thiolactonase and several indicators of vascular inflammation and the gene expression of PON2 in the peripheral blood mononuclear cell (PBMC) in the patients with type II diabetes mellitus. In this randomized, double-blind clinical trial, placebo-controlled, single-center, 36 men and women aged 35-50 years with type 2 diabetes are enrolled in the study from the Iranian Diabetes Association. After signing informed consent, all individuals complete a general information form. a 24-hour food recall for 3 days will be taken from the participants at the beginning and the end of the study,. Selected samples are randomly classified into 2 blocks of groups receiving supplement and placebo. Two groups will be classified (blocked) based on sex. The supplement group, will receive 2 g/day EPA for 8 weeks and the placebo group will also receive placebo (containing 2 g of edible paraffin) (similar in terms of color, shape and size). Patients are recommended to sustain their diets and medication dose (s) during the study and also advised to maintain a constant level of physical activity. Blood samples will be collected after 8-12 hours fasting and anthropocentric variables, biochemical parameters, target gene expression and physical activity before and after the trial will be measured.

Official Title
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The Effect of EPA on the Serum Activities of Paraoxonase 1, Homocystein, Thiolactonase and Some Indicators of Vascular Inflammation and PON2 Gene Expression in PBMC Ofthe Patients With Type II Diabetes

Conditions
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Diabetes Mellitus Type II

Intervention / Treatment
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* Dietary Supplement: EPA Supplement
* Dietary Supplement: EPA Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Willingness to collaborate in the study aged 35-50 years having a history of at least 1 year of type 2 diabetes mellitus before the participation in the study based on FBS ≥126 mg/dl or 2hPG ≥200 mg/dl (2-hour plasma glucose), 25≤BMI<30 kg/m2 Exclusion criteria: pregnant and breastfeeding women using insulin, alcohol consumption, smoking and other drugs taking drugs (lipid-lowering, β-blockers, diuretics, estrogens, progesterones, vitamin supplements and ω-3 fatty acid supplements followers of the special diet history of diabetic retinopathy or diabetic nephropathy type 1 diabetes mellitus and other disorders any need to take insulin, change in the dose (s) and type of medication or physical activity

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 50 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: EPA placebo<br>EPA- placebo softgel (Containing 2 g edible paraffin oil), 2 times/day, for 8 weeks | Dietary Supplement: EPA Placebo<br>* EPA- placebo softgel (Containing 2 g edible paraffin oil), 4 × 500 mg softgel daily, 2 times a day, for 8 weeks.<br>|
| Active Comparator: EPA supplement<br>EPA supplement softgel (containing 2 g EPA per day), 2 times/day, for 8 weeks. | Dietary Supplement: EPA Supplement<br>* EPA supplement, 4 × 500 mg softgel daily (2 g per day), 2 times a day, for 8 weeks.<br>* Other names: Eicosapentaenoic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c | Hemoglobin A1c (HbA1c) measurement by related kits according their protocols | Change from Baseline at 8 weeks after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PON2 gene expression | measurement of paraoxonase-2(PON-2) gene expression using quantitative Real-time PCR | Baseline, 8 weeks after the intervention | 
| Systolic blood pressure | Systolic blood pressure changes measurement by manometer | Change frome baseline at 8 weeks | 
| Diastolic blood pressure | Diastolic blood pressure changes measurement by manometer | Change frome baseline at 8 weeks | 
| serum paraoxonase-1(PON-1) activity | serum paraoxonase-1(PON-1) activity by kit according related protocol | Baseline, 8 weeks after the intervention | 
| PON1/HDL-c Ratio | calculating the ratio after measurement of PON1 and HDL-c by related kits according their protocols | Baseline, 8 weeks after the intervention | 
| serum paraoxonase lactonase (PON-HCTLase) activity | measurement of paraoxonase lactonase (PON-HCTLase) activity by related kit according its protocol | Baseline, 8 weeks after the intervention | 
| HDL-c | high density lipoprotein- cholesterol (HDL-c) measurement by related kits according their protocols | Baseline, 8 weeks after the intervention | 
| FBS | Fasting blood sugar (FBS) measurement by related kits according their protocols | Baseline, 8 weeks after the intervention | 
| HDL2-c | high density lipoprotein 2- cholesterol (HDL2-c) measurement by related kits according their protocols | Baseline, 8 weeks after the intervention | 
| HDL3-c | high density lipoprotein 3- cholesterol (HDL3-c) measurement by related kits according their protocols | Baseline, 8 weeks after the intervention | 
| Serum apo B | Serum apo-protein B measurement by related kits according their protocols | Baseline, 8 weeks after the intervention | 
| Serum apo A-I | Serum apo-protein A-I measurement by related kits according their protocols | Baseline, 8 weeks after the intervention | 
| apo B/apo A-I Ratio | calculating the ratio after measurement of apo B and apo A-1 by related kits according their protocols | Baseline, 8 weeks after the intervention | 
| Serum methionine | measurement of serum levels of methionine by related kit according its protocol | Baseline, 8 weeks after the intervention | 
| Serum malondialdehyde (MDA) | measurement of serum levels of malondialdehyde (MDA)by related kit according its protocol | Baseline, 8 weeks after the intervention | 
| Serum homocysteine (Hcy) | measurement of serum levels of homocysteine (Hcy) by related kit according its protocol | Baseline, 8 weeks after the intervention | 
| Serum sE-Selectin | measurement of serum levels of soluble E-Selectin by related kit according its protocol | Baseline, 8 weeks after the intervention | 
| sVCAM-1 | measurement of serum levels of soluble Vascular cell adhesion molecule-1 (VCAM-1) by related kit according its protocol | Baseline, 8 weeks after the intervention | 
| Serum cysteine | measurement of serum levels of cysteine by related kit according its protocol | Baseline, 8 weeks after the intervention | 
| Serum Lpa | measurement of serum levels of lipoprotein-a (Lpa)by related kit according its protocol | Baseline, 8 weeks after the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EPA, Paraoxonase 1, Paraoxonase 2, Type 2 diabetes