Effect of Metformin and Combination of Olive Oil Plus Nutritional Supplements on Inflammatory Markers IL-6 and IL-8 in PCOS.

Study Overview
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Brief Summary
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The investigators aim is to conduct randomized clinical trial, to determine the effects of metformin and combination of olive oil plus nutritional supplements on inflammatory markers IL-8 and IL6 in polycystic ovarian syndrome (PCOS). Women diagnosed with PCOS using Rotterdam diagnostic criteria according to which two out of three characters must be their in women of PCOS. The investigators propose that PCOS women have increase levels of IL-6 ,IL-8 and this therapy would have beneficial effects and is able to reduce their increase interleukins levels .

Detailed Description
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Poly cystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, it affects approximately 4% to 7% of women of child bearing age. PCOS is characterized by poly cystic ovaries, an-ovulation, and other associated features of hyperandrogenism It is pro inflammatory state which is related to insulin resistance, irregular menstruation(oligomenorrhea), type II diabetes, hyperinsulinemia and increased hair growth as signs and symptoms An anti-hyperglycemic agent such as Metformin improves glucose tolerance, and at cellular levels increase the action of insulin without affecting it's secretion. Insulin resistance, hyperinsulinemia and lipid abnormalities are managed by treatment with metformin. Several studies indicate a positive effect of metformin on both metabolic and reproductive aspects in female having PCOS. Metformin is known to reduce obesity and decrease other inflammatory biomarkers like serum c-reactive protein in female having PCOS. L-carnitine is synthesized by the human body as an endogenous compound, it plays a very important role in the metabolism of fatty acid. L-Carnitine is a cofactor and it help in the oxidation of fatty acids by transporting long-chain of fatty acids across mitochondrial membrane. LC levels are found reduced in patients having PCOS; therefore, for the proper management for insulin resistance and obesity in women adjunctive therapy of LC could be beneficial. Recent studies on olive oil shows that it helps in reducing fatty liver, while olive oil consumption had no effects on the lipid profile. Olive oil has excellent anti-inflammatory potentials against IL-6,IL-8 and TNF produced into the bloodstream as compared to metformin. As a result, it can be used in PCOS treatment. IL-6 shows an essential part in endocrine system as a major pro-inflammatory cytokine, particularly related to ovarian growth and the course of fertilization and implantation. IL-6 is involved in low grade chronic inflammation in female with PCOS2. IL-6 also showed to have an effect on insulin resistance and cardiovascular abnormalities . Elevated IL-6 levels is reported to be associated with increase weight, a major risk factor for type II diabetes. IL-8 is proinflammatory cytokine.Il-8 is chemoattractant and it activate neutrophils. Proinflammatory markers like il-6 and il-8 are involved in the development in development of insulin resistance in PCO. Insulin resistance is involved in exaggeration of inflammatory process. Arginine is amino acid by nature. It is an essential substrate for nitric oxide synthesis which is involved in insulin signaling. Its supplementation can improve metabolic disorders, immune function, wound healing, lean tissue mass, and brown adipose tissue growth.Co-q10 act as a cofactor in the electron transport chain and in the series of redox reaction which are crucial in the synthesis of adenosine tri phosphate. Co-Q10 is essential of the health of almost all organs and tissues because ATP is the soul requirement of all cellular functions. Coq-10 is the most important lipid antioxidants, it guards against the formation of free radicals and their alterations to proteins, lipids, and DNA. PCOS is an anti-inflammatory condition. Previous studies shows that level of certain cytokines are elevated in individual with PCOS. Studies related to inflammatory markers and PCOS are very few so, this research will help us in better understanding of inflammatory markers and PCOS and it will also help us in deciding a more better treatment plan for female patients having PCOS.The purpose of this study is to determine the effects of metformin and combination of olive oil plus nutritional supplements after 3 months, on inflammatory markers IL-8 and IL6 in polycystic ovarian syndrome

Official Title
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Effect of Metformin and Combination of Olive Oil Plus Nutritional Supplements on Inflammatory Markers IL-6 and IL-8 in PCOS.

Conditions
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PCO

Intervention / Treatment
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* Drug: OLIVE OIL 5ML/5MG (BD) NUTRITIONAL SACHET 2100MG (BD)
* Drug: Metformin (1000 mg Twice a day)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women diagnosed according to Rotterdam criteria (2 out of 3 should be present) Hyperandrogenism Polycystic ovaries Menstrual irregularities Age 18-34 years Exclusion Criteria: Previous history of Cushing's syndrome Women using other medications simultaneously which may affect hormonal changes Previous history of ovarian surgery Congenital adrenal hyperplasia Thyroid diseases Autoimmune diseases •

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 34 Years

Sexes Eligible for Study
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Female

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Combination Therapy Group<br>ARM# 1 OLIVE OIL 5ML/5MG (BD) NUTRITIONAL SACHET 2100MG (BD) | Drug: OLIVE OIL 5ML/5MG (BD) NUTRITIONAL SACHET 2100MG (BD)<br>* 44 Patients with PCOS receiving olive oil 5ML/5MG (BD) nutritional sachet 2100MG (BD<br>|
| Other: Standard Therapy Group<br>ARM # 2 METFORMIN 1000MG (BD) | Drug: Metformin (1000 mg Twice a day)<br>* 44 Patients with PCOS receiving Metformin 1000mg (BD)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukin 6 level | measurement of IL-6 level vis ELISA | 3 months | 
| Interleukin 8 level | measurement of IL-8 level vis ELISA | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin, L-Carnitine, Interleukin-6, L-arginine, CoQ-10