- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT02939079
Evaluating of the Effect of Fingolimod With Fish Oil on Relapsing-Remitting Multiple Sclerosis Patients
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
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
- Fas 3
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Trippel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: Fingolimod and Fish Oil
Fingolimod 0.5 mg capsule daily by mouth and Fish Oil 1 g capsule daily by mouth for one year.
|
Produced by Osveh ® Pharm Company in Iran
Andra namn:
produced by Zahravi ® Pharm Company in Iran
Andra namn:
|
|
Aktiv komparator: Fingolimod and Placebo
Fingolimod 0.5 mg capsule daily by mouth and Placebo capsule daily by mouth for one year.
|
Produced by Osveh ® Pharm Company in Iran
Andra namn:
placebo capsules to mimic Fish Oil 1 g capsules
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Serum Level of TNF-α
Tidsram: 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.
|
Baseline
|
|
Serum Level of IL1b
Tidsram: 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.
|
Baseline
|
|
Serum Level of IL6
Tidsram: 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.
|
Baseline
|
|
Serum Level of IFN-gamma
Tidsram: 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.
|
Baseline
|
|
Serum Level of TNF-α
Tidsram: 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 months after intervention
|
|
Serum Level of TNF-α
Tidsram: 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.
|
1 year after intervention
|
|
Serum Level of IL1b
Tidsram: 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 months after intervention
|
|
Serum Level of IL1b
Tidsram: 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.
|
1 year after intervention
|
|
Serum Level of IL6
Tidsram: 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 months after intervention
|
|
Serum Level of IL6
Tidsram: 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.
|
1 year after intervention
|
|
Serum Level of IFN-gamma
Tidsram: 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 months after intervention
|
|
Serum Level of IFN-gamma
Tidsram: 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.
|
1 year after intervention
|
Samarbetspartners och utredare
Samarbetspartners
Utredare
- Studiestol: Shaygannejad Shaygannejad, M.D., Isfahan University of Medical Sciences
Publikationer och användbara länkar
Allmänna publikationer
- Aktas O, Kury 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.
- 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.
- 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. doi: 10.1016/0165-5728(94)00140-j.
- 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. doi: 10.1034/j.1600-0404.2000.102003143.x.
- Ramirez-Ramirez V, Macias-Islas MA, Ortiz GG, Pacheco-Moises F, Torres-Sanchez ED, Sorto-Gomez TE, Cruz-Ramos JA, Orozco-Avina G, Celis de la Rosa AJ. Efficacy of fish oil on serum of TNF alpha , IL-1 beta , 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, Lilleas F, Pedersen T, Bjornara B, Dalene F, Kleveland G, Schepel J, Olsen IC, Myhr KM. omega-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.
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Patologiska processer
- Sjukdomar i nervsystemet
- Immunsystemets sjukdomar
- Demyeliniserande autoimmuna sjukdomar, CNS
- Autoimmuna sjukdomar i nervsystemet
- Demyeliniserande sjukdomar
- Autoimmuna sjukdomar
- Multipel skleros
- Skleros
- Multipel skleros, skov-remitterande
- Läkemedels fysiologiska effekter
- Molekylära mekanismer för farmakologisk verkan
- Immunsuppressiva medel
- Immunologiska faktorer
- Sfingosin 1 fosfatreceptormodulatorer
- Fingolimod hydroklorid
Andra studie-ID-nummer
- 293396
Plan för individuella deltagardata (IPD)
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