Evaluating of the Effect of Fingolimod With Fish Oil on Relapsing-Remitting Multiple Sclerosis Patients

Study Overview
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Brief Summary
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This study evaluates the effect of adding fish oil to Fingolimod on some serum cytokines in patients with Relapsing-Remitting Multiple Sclerosis.

Detailed Description
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Multiple Sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory demyelinative lesions in central nervous system. Relapsing-Remitting MS is the most common form of the disease observed in 85% of patients. This form presents with acute or sub-acute onset of neurological symptoms and patients may fully or partially recover and relapses may occur from time to time. Regarding MS pathogenesis, the findings suggest the role of environmental factors in triggering the innate immune system and activating T cells and the onset of a chronic inflammatory response against myelin antigens in the central nervous system in people who are genetically prone to the disease. Among immune cells, T helper 17 (Th17) plays an important role in autoimmune response and are shown to be involved in clinical course of Relapsing-Remitting MS. Th17 cell differentiation is controlled by several cytokines, including interleukin-6 (IL-6), interleukin-1b (IL-1b) and interleukin-10 (IL-10). Also, IL 6 have an inhibitory effect on Th17 cell differentiation through increased production of interferon-gamma (IFN-gamma) and IL 10. Currently, immunomodulatory drugs are considered as the first line treatment in MS. Fingolimod is the first oral immunomodulatory medication used for Relapsing-Remitting MS. It is phosphorylated by crossing the blood-brain barrier and is converted to its active metabolite, Fingolimod-P. This metabolite acts as a Sphingosine-1-phosphate receptor (S1PR1) on oligodendrocytes, microglias, astrocytes, and neurons and inhibits the entry of lymphocytes into the central nervous system. Therefore, it reduces demyelination and may also lead to remyelination. Nutrition is known as a possible environmental factor in pathogenesis of MS. Positive clinical and biological effects of dietary supplements containing polyunsaturated fatty acids omega -3 (PUFA) in the course of autoimmune diseases such as MS have been studied. High levels of PUFA is found in fish oil which is also known as an antioxidant, anti-inflammatory and immunomodulatory agent. Several studies have evaluated the effect of fish oil as a dietary supplement in the treatment of MS however, conflicting findings are reported. In this study, the investigators aim to evaluate the effect of Fingolimod with Fish oil compared to Fingolimod with placebo on TNF-α, IL1b, IL6, and IFN-gamma in patients with Relapsing-Remitting Multiple sclerosis.

Official Title
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Evaluating the Effect of Fingolimod With Fish Oil Compared to Fingolimod With Placebo on Tumor Necrosis Factor-α , Interleukin1b , Interleukin6, and Interferon-gamma in Patients With Relapsing-Remitting Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Fingolimod
* Dietary Supplement: Fish Oil
* Drug: Placebo (for Fish Oil)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with relapsing-remitting multiple sclerosis according to McDonald's criteria (2010) Age between 18 and 45 years Expanded Disability Status Scale (EDSS) between 0-5 History of at least one relapse during the last year Intolerance or serious complications when receiving interferons Not receiving interferons in the last two months Not having relapse in the last 30 days Negative pregnancy test History of varicella or varicella vaccination, or positive test for anti-varicella antibodies Not to take any medication or dietary complement without permission of the physician Filling informed consent Exclusion Criteria: Having chronic and infectious diseases History of cardiovascular diseases Taking corticosteroids in the last 30 days Taking chemotherapy agents such as Cyclophosphamide Patients who have taken fingolimod before Patients who experience relapse during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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 |
| --- | --- |
| Experimental: Fingolimod and Fish Oil<br>Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. | Drug: Fingolimod<br>* Produced by Osveh ® Pharm Company in Iran<br>* Other names: Fingolid ®;Dietary Supplement: Fish Oil<br>* produced by Zahravi ® Pharm Company in Iran<br>* Other names: OMEGAMAX ®;|
| Active Comparator: Fingolimod and Placebo<br>Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. | Drug: Fingolimod<br>* Produced by Osveh ® Pharm Company in Iran<br>* Other names: Fingolid ®;Drug: Placebo (for Fish Oil)<br>* placebo capsules to mimic Fish Oil 1 g capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Level of TNF-α | 5 cc of venous blood is taken from patients and are kept in test tubes without ethylenediaminetetraacetic acid (EDTA). Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | Baseline | 
| Serum Level of IL1b | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | Baseline | 
| Serum Level of IL6 | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | Baseline | 
| Serum Level of IFN-gamma | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | Baseline | 
| Serum Level of TNF-α | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | 6 months after intervention | 
| Serum Level of TNF-α | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | 1 year after intervention | 
| Serum Level of IL1b | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | 6 months after intervention | 
| Serum Level of IL1b | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | 1 year after intervention | 
| Serum Level of IL6 | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | 6 months after intervention | 
| Serum Level of IL6 | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | 1 year after intervention | 
| Serum Level of IFN-gamma | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | 6 months after intervention | 
| Serum Level of IFN-gamma | 5 cc of venous blood is taken from patients and are kept in test tubes without EDTA. Test tubes are kept one hour immobilized so that clotted blood and serum are separated. Then, the serum is divided into four samples of 0.5 cc for immunologic testing of all primary outcomes. Immunologic testing is performed by sandwich ELISA method using Diaclone ® kits (made in France) and according to manufacturer's instructions. | 1 year after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Fingolimod, Fish Oil