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

• Sponsor: Isfahan University of Medical Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT02939079
• Collaborator: Shiraz University of Medical Sciences (Other)
• Enrollment: 50
• Arms: 2
• Duration (Months): 18

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Fingolimod; Dietary Supplement: Fish Oil; Drug: Placebo (for Fish Oil)	Phase 2/Phase 3

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Apr 1, 2015
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fingolimod and Fish Oil Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year.	Drug: Fingolimod; Produced by Osveh ® Pharm Company in Iran; Other Names: Fingolid ® ; Dietary Supplement: Fish Oil; produced by Zahravi ® Pharm Company in Iran; Other Names: CODLIVE ® OMEGAMAX ®
Active Comparator: Fingolimod and Placebo Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year.	Drug: Fingolimod; Produced by Osveh ® Pharm Company in Iran; Other Names: Fingolid ® ; Drug: Placebo (for Fish Oil); placebo capsules to mimic Fish Oil 1 g capsules

Outcome Measures

Primary Outcome Measures

1. Serum Level of TNF-α [Baseline]

   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.

2. Serum Level of IL1b [Baseline]

   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.

3. Serum Level of IL6 [Baseline]

   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.

4. Serum Level of IFN-gamma [Baseline]

   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.

5. Serum Level of TNF-α [6 months after intervention]

   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. Serum Level of TNF-α [1 year after intervention]

   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.

7. Serum Level of IL1b [6 months after intervention]

   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.

8. Serum Level of IL1b [1 year after intervention]

   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.

9. Serum Level of IL6 [6 months after intervention]

   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.

10. Serum Level of IL6 [1 year after intervention]

    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.

11. Serum Level of IFN-gamma [6 months after intervention]

    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.

12. Serum Level of IFN-gamma [1 year after intervention]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Isfahan University of Medical Sciences
• Shiraz University of Medical Sciences

Investigators

• Study Chair: Shaygannejad Shaygannejad, M.D., Isfahan University of Medical Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

• Aktas O, Küry P, Kieseier B, Hartung HP. Fingolimod is a potential novel therapy for multiple sclerosis. Nat Rev Neurol. 2010 Jul;6(7):373-82. doi: 10.1038/nrneurol.2010.76. Epub 2010 Jun 15. Review.
• Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, Aradhye S, Burtin P. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov. 2010 Nov;9(11):883-97. doi: 10.1038/nrd3248. Epub 2010 Oct 29. Review.
• Gallai V, Sarchielli P, Trequattrini A, Franceschini M, Floridi A, Firenze C, Alberti A, Di Benedetto D, Stragliotto E. Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. J Neuroimmunol. 1995 Feb;56(2):143-53.
• Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, Selmaj K, Agoropoulou C, Leyk M, Zhang-Auberson L, Burtin P; FREEDOMS Study Group. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4;362(5):387-401. doi: 10.1056/NEJMoa0909494. Epub 2010 Jan 20.
• Nordvik I, Myhr KM, Nyland H, Bjerve KS. Effect of dietary advice and n-3 supplementation in newly diagnosed MS patients. Acta Neurol Scand. 2000 Sep;102(3):143-9.
• Ramirez-Ramirez V, Macias-Islas MA, Ortiz GG, Pacheco-Moises F, Torres-Sanchez ED, Sorto-Gomez TE, Cruz-Ramos JA, Orozco-Aviña G, Celis de la Rosa AJ. Efficacy of fish oil on serum of TNF α , IL-1 β , and IL-6 oxidative stress markers in multiple sclerosis treated with interferon beta-1b. Oxid Med Cell Longev. 2013;2013:709493. doi: 10.1155/2013/709493. Epub 2013 Jun 18.
• Torkildsen O, Wergeland S, Bakke S, Beiske AG, Bjerve KS, Hovdal H, Midgard R, Lilleås F, Pedersen T, Bjørnarå B, Dalene F, Kleveland G, Schepel J, Olsen IC, Myhr KM. ω-3 fatty acid treatment in multiple sclerosis (OFAMS Study): a randomized, double-blind, placebo-controlled trial. Arch Neurol. 2012 Aug;69(8):1044-51. doi: 10.1001/archneurol.2012.283.

• Responsible Party: Vahid Shaygannejad, Associate Professor of Neurology, Isfahan University of Medical Sciences
• ClinicalTrials.gov Identifier: NCT02939079
• Other Study ID Numbers: 293396
• First Posted: Oct 19, 2016
• Last Update Posted: May 14, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Vahid Shaygannejad, Associate Professor of Neurology, Isfahan University of Medical Sciences: Multiple Sclerosis; Fingolimod; Fish Oil
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Fingolimod Hydrochloride

Study Results

Participant Flow

Recruitment Details	The recruitment period started on April 2015. 74 patients were screened initially and 50 of them were recruited. All the patients were recruited from the neurology department of Kashani hospital, Isfahan, iran. They were patients referred to the neurology department (multiple sclerosis clinic) for evaluation and treatment.
Pre-assignment Detail	After recruitment, no medication was prescribed for the patients for two months as the wash-out period. Then patients were assigned to study groups.

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Period Title: Overall Study
STARTED	25	25
COMPLETED	21	20
NOT COMPLETED	4	5

Baseline Characteristics

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo	Total
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules	Total of all reporting groups
Overall Participants	21	20	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.19 (9.97)	31.40 (8.41)	33.34 (9.21)
Sex: Female, Male (Count of Participants)
Female	13 61.9%	16 80%	29 70.7%
Male	8 38.1%	4 20%	12 29.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Iran	21 100%	20 100%	41 100%
Dietary habits, Categorical (seafood meals per month) (Count of Participants)
0-1 meals per month	19 90.5%	18 90%	37 90.2%
2-4 meals per month	2 9.5%	2 10%	4 9.8%
>4 meals per month	0 0%	0 0%	0 0%
EDSS (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.10 (1.28)	2.55 (1.38)	2.83 (1.33)

Outcome Measures

1. Primary Outcome

Title	Serum Level of TNF-α
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Per-protocol analysis

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	37.16 (92.74)	28.79 (47.46)

2. Primary Outcome

Title	Serum Level of IL1b
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	13.76 (0.74)	14 (1.03)

3. Primary Outcome

Title	Serum Level of IL6
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	6.19 (0.35)	6.33 (0.58)

4. Primary Outcome

Title	Serum Level of IFN-gamma
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	6.38 (1.51)	6.98 (3.87)

5. Primary Outcome

Title	Serum Level of TNF-α
Description	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.
Time Frame	6 months after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	28.03 (60.36)	17.18 (18.88)

6. Primary Outcome

Title	Serum Level of TNF-α
Description	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.
Time Frame	1 year after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	21.20 (36.45)	16.47 (16.64)

7. Primary Outcome

Title	Serum Level of IL1b
Description	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.
Time Frame	6 months after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	13.61 (0.58)	13.47 (0.74)

8. Primary Outcome

Title	Serum Level of IL1b
Description	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.
Time Frame	1 year after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	13.17 (0.52)	13.15 (0.61)

9. Primary Outcome

Title	Serum Level of IL6
Description	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.
Time Frame	6 months after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	6.65 (2.11)	6.17 (0.71)

10. Primary Outcome

Title	Serum Level of IL6
Description	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.
Time Frame	1 year after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	6.17 (0.76)	6.05 (0.47)

11. Primary Outcome

Title	Serum Level of IFN-gamma
Description	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.
Time Frame	6 months after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	5.71 (0.57)	6.37 (1.77)

12. Primary Outcome

Title	Serum Level of IFN-gamma
Description	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.
Time Frame	1 year after intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod and Fish Oil	Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran	Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
Measure Participants	21	20
Mean (Standard Deviation) [Pg/ml]	5.92 (1.31)	5.99 (0.84)

Adverse Events

Time Frame	Patients were evaluated in the study for one year and were observed for adverse events during this period.
Adverse Event Reporting Description	Adverse events were collected through follow up phone calls and visits.
Arm/Group Title	Fingolimod and Fish Oil		Fingolimod and Placebo
Arm/Group Description	Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Fish Oil: produced by Zahravi ® Pharm Company in Iran		Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year. Fingolimod: Produced by Osveh ® Pharm Company in Iran Placebo (for Fish Oil): placebo capsules to mimic Fish Oil 1 g capsules
All Cause Mortality
	Fingolimod and Fish Oil		Fingolimod and Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)
Serious Adverse Events
	Fingolimod and Fish Oil		Fingolimod and Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/25 (8%)		2/25 (8%)
Cardiac disorders
Hypotension and bradycardia	2/25 (8%)	2	2/25 (8%)	2
Other (Not Including Serious) Adverse Events
	Fingolimod and Fish Oil		Fingolimod and Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)

Limitations/Caveats

Small sample size and trial duration; Not giving patients specific nutritional diets; Receiving tocopherol in the placebo capsules which may confound our findings considering the antioxidant nature of tocopherol; Lower doses of fish oil prescribed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.