Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants: Study protocol for an exploratory randomized double- blind placebo-controlled trial

Trials

Volumn 14, Issue 1, 2013, Pages

  O'Connell, Karen ^a   Kelly, Siobhan ^a   Kinsella, Katie ^a   Jordan, Sinead ^a   Kenny, Orla ^a   Murphy, David ^a   Heffernan, Eric ^a   O'Laoide, Risteard ^a   O'Shea, Donal ^a   McKenna, Carmel ^a   Cassidy, Lorraine ^b   Fletcher, Jean ^c   Walsh, Cathal ^c   Brady, Jennifer ^d   McGuigan, Christopher ^a   Tubridy, Niall ^a   Hutchinson, Michael ^a  

^a ST VINCENT S UNIVERSITY HOSPITAL   (Ireland)

^b ROYAL VICTORIA EYE AND EAR HOSPITAL   (Ireland)

^c TRINITY COLLEGE DUBLIN   (Ireland)

^d MATER MISERICORDIAE UNIVERSITY HOSPITAL   (Ireland)

Author keywords

Cholecalciferol; Clinical trial; Clinically isolated syndrome; Immunomodulation; Multiple sclerosis; Vitamin D

Indexed keywords

COLECALCIFEROL; GADOLINIUM; PLACEBO;

ADULT; ARTICLE; CD4+ T LYMPHOCYTE; CLINICAL ARTICLE; CONTROLLED STUDY; CYTOKINE RESPONSE; DEMYELINATING DISEASE; DISEASE COURSE; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFECT; FEMALE; HUMAN; IMMUNE RESPONSE; MALE; NUCLEAR MAGNETIC RESONANCE IMAGING; PERIPHERAL BLOOD MONONUCLEAR CELL; PHASE 2 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL;

BIOLOGICAL MARKERS; BRAIN; CD4 LYMPHOCYTE COUNT; CHOLECALCIFEROL; CLINICAL PROTOCOLS; CYTOKINES; DEMYELINATING DISEASES; DISEASE PROGRESSION; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; HEALTHY VOLUNTEERS; HUMANS; IRELAND; LEUKOCYTES, MONONUCLEAR; MAGNETIC RESONANCE IMAGING; MULTIPLE SCLEROSIS; RESEARCH DESIGN; TIME FACTORS; TREATMENT OUTCOME; VITAMIN D;

EID: 84883094436     PISSN: None     EISSN: 17456215     Source Type: Journal    
DOI: 10.1186/1745-6215-14-272     Document Type: Article

References (35)

1. Ebers G. Environmental factors and multiple sclerosis. Lancet Neurol 2008, 7:268-277. 10.1016/S1474-4422(08)70042-5, 18275928.
2. Simpson S, Blizzard L, Otahal P, Van der Mei I, Taylor B. Latitude is significantly associated with the prevalence of multiple sclerosis: a meta-analysis. J Neurol Neurosurg Psychiatry 2011, 82(10):1132-1141. 10.1136/jnnp.2011.240432, 21478203.
3. Ramagopalan SV, Handel AE, Giovannoni G, Rutherford Siegel S, Ebers GC, Chaplin G. Relationship of UV exposure to prevalence of multiple sclerosis in England. Neurology 2011, 76:1410-1414. 10.1212/WNL.0b013e318216715e, 3087404, 21502600.
4. Orton SM, Wald L, Confavreux C, Vukusic S, Krohn JP, Ramagopalan SV, Herrera BM, Sadovnick AD, Ebers GC. Association of UV radiation with multiple sclerosis prevalence and sex ratio in France. Neurology 2011, 76:425-431. 10.1212/WNL.0b013e31820a0a9f, 3034408, 21282589.
5. Dean G. Annual incidence, prevalence, and mortality of multiple sclerosis in white South-African-born and in white immigrants to South Africa. BMJ 1967, 2:724-730. 10.1136/bmj.2.5554.724, 1841809, 6025978.
6. Hammond SR, McLeod JG, Millingen KS, Stewart-Wynne EG, English D, Holland JT, McCall MG. The epidemiology of multiple sclerosis in 3 Australian cities: Perth, Newcastle and Hobart. Brain 1988, 111:1-25. 10.1093/brain/111.1.1, 3365543.
7. Van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Taylor BV, Kilpatrick T, Butzkueven H, McMichael AJ. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol 2007, 254:581-590. 10.1007/s00415-006-0315-8, 17426912.
8. Hill TR, Flynn A, Kiely M, Cashman KD. Prevalence of suboptimal vitamin D status in young, adult and elderly Irish subjects. Ir Med J 2006, 99(2):48-49.
9. Lonergan R, Kinsella K, Fitzpatrick P, Brady J, Murray B, Dunne C, Hagan R, Duggan M, Jordan S, McKenna M, Hutchinson M, Tubridy N. Multiple sclerosis prevalence in Ireland: relationship to vitamin D status and HLA genotype. J Neurol Neurosurg Psychiatry 2011, 82:317-322. 10.1136/jnnp.2010.220988, 21248317.
10. Soilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna JP, Lilius EM, Mononen I. A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry 2008, 79:152-157. 10.1136/jnnp.2006.105320, 17578859.
11. Smolders J, Menheere P, Kessels A, Damoiseaux J, Hupperts R. Association of vitamin D metabolite levels with relapse rate and disability in multiple sclerosis. Mult Scler 2008, 14(9):1220-1224. 10.1177/1352458508094399, 18653736.
12. Mowry E, Krupp L, Milazzo M, Chabas D, Strober JB, Belman AL, McDonald JC, Oksenberg JR, Bacchetti P, Waubant E. Vitamin D status is associated with relapse rate in pediatric-onset MS. Ann Neurol 2010, 67:618-624.
13. Simpson S, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, Dwyer T, Gies P, van der Mei I. Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol 2010, 68:193-203.
14. Mirzaei F, Michels KB, Munger K, O'Reilly E, Chitnis T, Forman MR, Giovannucci E, Rosner B, Ascherio A. Gestational vitamin D and the risk of multiple sclerosis in offspring. Ann Neurol 2011, 70:30-40. 10.1002/ana.22456, 3205990, 21786297.
15. Salzer J, Hallmans G, Nyström M, Stenlund H, Wadell G, Sundström P. Vitamin D as a protective factor in multiple sclerosis. Neurology 2012, 79:2140-2145. 10.1212/WNL.0b013e3182752ea8, 23170011.
16. Dobson R, Giovannoni G, Ramagopalan S. The month of birth effect in multiple sclerosis: systematic review, meta-analysis and effect of latitude. J Neurol Neurosurg Psychiatry 2012, 84(4):427-432.
17. Goldberg P, Fleming MC, Picard EH. Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Med Hypotheses 1986, 21:193-200. 10.1016/0306-9877(86)90010-1, 3537648.
18. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003, 77:204-210.
19. Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch D-M, Cheung R, Gagne D, D'Souza C, Ursell M, O'Connor P. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 2010, 74:1852-1859. 10.1212/WNL.0b013e3181e1cec2, 2882221, 20427749.
20. The IFNB multiple sclerosis study group: Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993, 43(4):655-661. The IFNB.
21. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet 1998, 35(9139):1498-1504. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group.
22. Correale J, Ysrraelit MC, Gaitán MI. Immunomodulatory effects of vitamin D in MS. Brain 2009, 132:1146-1160. 10.1093/brain/awp033, 19321461.
23. Adorini L, Penna G. Control of immune diseases by the vitamin D endocrine system. Nature Clin Pract Rheumat 2008, 4:404-412.
24. Bhalla AK, Amento EP, Serog B, Glimcher LH. 1,25-dihydroxyvitamin D3 inhibits antigen-induced T cell activation. J Immunol 1984, 133:1748-1754.
25. Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25- dihydroxyvitamin D3 on human B cell differentiation. J Immunol 2007, 179:1634-1647.
26. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O'Garra A. 1alpha,25- Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 2001, 167:4974-4980.
27. Dörr J, Ohlraun S, Skarabis H, Paul F. Efficacy of vitamin D supplementation in multiple sclerosis (EVIDIMS Trial): study protocol for a randomized controlled trial. Trials 2012, 13:15. 10.1186/1745-6215-13-15, 3298796, 22316314.
28. Smolders J, Hupperts R, Barkhof F, Grimaldi LM, Holmoy T, Killestein J, Rieckmann P, Schluep M, Vieth R, Hostalek U, Ghazi-Visser L, Beelke M, Beelke M. SOLAR study group: efficacy of vitamin d3 as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon β-1a: a phase II, multicenter, double-blind, randomized, placebo-controlled trial. J Neurol Sci 2011, 311(1-2):44-49.
29. Hutchinson M, Zajicek J. Clinically isolated syndrome: a protected zone for trials of new therapies?. Mult Scler 2010, 16:754-755. 10.1177/1352458510366015, 20427416.
30. GraphPad. http://www.graphpad.com/quickcalcs/randomize1.cfm.
31. Polman C, Reingold S, Banwell B, Clanet M, Cohen J, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin F, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson A, Waubant E, Weinshenker B, Wolinsky J. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011, 69(2):292-302. 10.1002/ana.22366, 3084507, 21387374.
32. Allen AC, Kelly S, Basdeo SA, Kinsella K, Mills KHG, Tubridy N, Walsh C, Brady J, Hutchinson M, Fletcher JM. A pilot study of the immunological effects of high dose vitamin D in healthy volunteers. Mult Scler 2012, 18(12):1797-1800. 10.1177/1352458512442992, 22457344.
33. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society Evaluation, treatment and prevention of vitamin D deficiency. An endocrine society clinical practice guideline. 2011, 96:1911-30. Endocrine Society.
34. Vieth R. Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr 2006, 136:1117-1122.
35. Vieth R, Kimball S, Hu A, Walfish PG. Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Nutr J 2004, 3:1-8. 10.1186/1475-2891-3-1, 333426, 14725716.