Selenium supplementation for patients with Graves-hyperthyroidism (the GRASS trial): study protocol for a randomized controlled trial
详细信息 查看全文
- 作者：Torquil Watt (93)
Per Cramon (93)
Jakob Bue Bjorner (94) (95)
Steen Joop Bonnema (96)
Ulla Feldt-Rasmussen (93)
Christian Gluud (97)
Jeppe Gram (98)
Jane Lindschou Hansen (97)
Laszlo Hegedüs (96)
Nils Knudsen (99)
Pernille Bach-Mortensen (100)
Runa Nols?e (101)
Birte Nygaard (102)
Flemming Pociot (103)
Maria Skoog (97)
Per Winkel (97)
?se Krogh Rasmussen (93) - 关键词：Graves' disease ; Selenium supplementation ; Pragmatic trial ; Quality of life ; ThyPRO
- 刊名：Trials
- 出版年：2013
- 出版时间：December 2013
- 年：2013
- 卷：14
- 期：1
- 全文大小：275KB
- 参考文献：1. Cerqueira C, Knudsen N, Ovesen L, Perrild H, Rasmussen LB, Laurberg P, Jorgensen T: Association of iodine fortification with incident use of antithyroid medication–a Danish Nationwide Study. / J Clin Endocrinol Metab 2009, 94:2400-405. CrossRef
2. Hegedus L: Treatment of Graves' hyperthyroidism: evidence-based and emerging modalities. / Endocrinol Metab Clin North Am 2009, 38:355-1. CrossRef
3. Watt T, Groenvold M, Rasmussen AK, Bonnema SJ, Hegedüs L, Bjorner JB, Feldt-Rasmussen U: Quality of life in patients with benign thyroid disorders. / A review. Eur J Endocrinol 2006, 154:501-10. CrossRef
4. Rasmussen LB, Mejborn H, Andersen NL, Dragsted LO, Krogholm KS, Larsen EH: / Selen og Sundhed. Copenhagen: Danmarks F?devareforskning; 2006.
5. Duntas LH: Selenium and the thyroid: a close-knit connection. / J Clin Endocrinol Metab 2010, 95:5180-188. CrossRef
6. Food and Nutrition Board IoM: Dietary reference intakes for vitamin C, vitamin E, selenium and carotenoids. In / Food and Nutrition Board, I.o.M. Edited by: Poillon F, Newberry S. Washington, D.C: National Academy Press; 2000:1.
7. Scientific Committee on Food: / Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level for Selenium. 1. 2000. Brussels: European Commission. Scientific Committee on Food; 2000.
8. Marcocci C, Leo M, Altea MA: Oxidative stress in Graves' disease. / European Thyroid Journal 2012, 1:80-7. CrossRef
9. Duntas LH: The role of selenium in thyroid autoimmunity and cancer. / Thyroid 2006, 16:455-60. CrossRef
10. Marcocci C, Kahaly GJ, Krassas GE, Bartalena L, Prummel M, Stahl M, Altea MA, Nardi M, Pitz S, Boboridis K, Sivelli P, von AG, Mourits MP, Baldeschi L, Bencivelli W, Wiersinga W: Selenium and the course of mild Graves' orbitopathy. / N Engl J Med 2011, 364:1920-931. CrossRef
11. Vrca VB, Skreb F, Cepelak I, Romic Z, Mayer L: Supplementation with antioxidants in the treatment of Graves' disease; the effect on glutathione peroxidase activity and concentration of selenium. / Clin Chim Acta 2004, 341:55-3. CrossRef
12. Vrca VB, Skreb F, Cepelak I, Mayer L: Supplementation with antioxidants in the treatment of Graves' disease: the effect on the extracellular antioxidative parameters. / Acta Pharm 2004, 54:79-9.
13. Wertenbruch T, Willenberg HS, Sagert C, Nguyen TB, Bahlo M, Feldkamp J, Groeger C, Hermsen D, Scherbaum WA, Schott M: Serum selenium levels in patients with remission and relapse of graves' disease. / Med Chem 2007, 3:281-84. CrossRef
14. Gartner R, Gasnier BC, Dietrich JW, Krebs B, Angstwurm MW: Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. / J Clin Endocrinol Metab 2002, 87:1687-691. CrossRef
15. Gartner R, Gasnier BC: Selenium in the treatment of autoimmune thyroiditis. / Biofactors 2003, 19:165-70. CrossRef
16. Duntas LH, Mantzou E, Koutras DA: Effects of a six month treatment with selenomethionine in patients with autoimmune thyroiditis. / Eur J Endocrinol 2003, 148:389-93. CrossRef
17. Turker O, Kumanlioglu K, Karapolat I, Dogan I: Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses. / J Endocrinol 2006, 190:151-56. CrossRef
18. Mazokopakis EE, Papadakis JA, Papadomanolaki MG, Batistakis AG, Giannakopoulos TG, Protopapadakis EE, Ganotakis ES: Effects of 12 months treatment with L-selenomethionine on serum anti-TPO Levels in Patients with Hashimoto's thyroiditis. / Thyroid 2007, 17:609-12. CrossRef
19. Nacamulli D, Mian C, Petricca D, Lazzarotto F, Barollo S, Pozza D, Masiero S, Faggian D, Plebani M, Girelli ME, Mantero F, Betterle C: Influence of physiological dietary selenium supplementation on the natural course of autoimmune thyroiditis. / Clin Endocrinol (Oxf) 2010, 73:535-39.
20. Karanikas G, Schuetz M, Kontur S, Duan H, Kommata S, Schoen R, Antoni A, Kletter K, Dudczak R, Willheim M: No immunological benefit of selenium in consecutive patients with autoimmune thyroiditis. / Thyroid 2008, 18:7-2. CrossRef
21. Pentel P, Fletcher D, Jentzen J: Fatal acute selenium toxicity. / J Forensic Sci 1985, 30:556-62.
22. H?gberg J, Alexander J: Selenium. In / Handbook on the toxicology of metals. Edited by: Friberg L, Nordberg GF, Vouk VB. Amsterdam: Elsevier; 1986:482-20.
23. Yang GQ, Wang SZ, Zhou RH, Sun SZ: Endemic selenium intoxication of humans in China. / Am J Clin Nutr 1983, 37:872-81.
24. Longnecker MP, Taylor PR, Levander OA, Howe M, Veillon C, McAdam PA, Patterson KY, Holden JM, Stampfer MJ, Morris JS: Selenium in diet, blood, and toenails in relation to human health in a seleniferous area. / Am J Clin Nutr 1991, 53:1288-294.
25. Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL, Taylor JR: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. / JAMA 1996, 276:1957-963. CrossRef
26. Rayman MP: The use of high-selenium yeast to raise selenium status: how does it measure up? / Br J Nutr 2004, 92:557-73. CrossRef
27. International Conference on Harmonisation Guideline for International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use: / Guideline for Good Clinical Practice E6 (R1). ICH Harmonised Tripartite Guideline. 10--1996. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6_R1/Step4/E6_R1__Guideline.pdf
28. Dupont WD, Plummer WD Jr: Power and sample size calculations. A review and computer program. / Control Clin Trials 1990, 11:116-28. CrossRef
29. Lantz M, Abraham-Nordling M, Svensson J, Allin G, Allengren B: Immigration and the incidence of Graves' thyrotoxicosis, thyrotoxic multinodular goiter and solitary toxic adenoma. / Eur J Endocrinol 2009, 160:201-06. CrossRef
30. Dmitrienko A, Tamhane AC, Wiens BL: General multistage gatekeeping procedures. / Biom J 2008, 50:667-77. CrossRef
31. International Committee of Medical Journal Editors: Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Ethical Considerations in the Conduct and Reporting of Research: Authorship and Contributorship. 2010.
32. Ware JH, Hamel MB: Pragmatic trials–guides to better patient care? / N Engl J Med 2011, 364:1685-687. CrossRef - 作者单位：Torquil Watt (93)
Per Cramon (93)
Jakob Bue Bjorner (94) (95)
Steen Joop Bonnema (96)
Ulla Feldt-Rasmussen (93)
Christian Gluud (97)
Jeppe Gram (98)
Jane Lindschou Hansen (97)
Laszlo Hegedüs (96)
Nils Knudsen (99)
Pernille Bach-Mortensen (100)
Runa Nols?e (101)
Birte Nygaard (102)
Flemming Pociot (103)
Maria Skoog (97)
Per Winkel (97)
?se Krogh Rasmussen (93)
93. Department of Medical Endocrinology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, DK, 2100, Denmark
94. National Research Centre for the Working Environment, Copenhagen, Denmark
95. Institute of Public Health Science, University of Copenhagen, Copenhagen, Denmark
96. Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark
97. Copenhagen Trial Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
98. Department of Endocrinology, Hospital of Southwest Denmark Esbjerg, Esbjerg, Denmark
99. Department of Endocrinology and Gastroenterology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark
100. Department of Endocrinology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark
101. Department of Cardiology and Endocrinology, Endocrine Unit, Copenhagen University Hospital Hiller?d, Hiller?d, Denmark
102. Department of Internal Medicine, Endocrine Unit, Copenhagen University Hospital Herlev, Copenhagen, Denmark
103. Glostrup Research Institute, Copenhagen University Hospital Glostrup, Copenhagen, Denmark
文摘
Background Graves-hyperthyroidism is an autoimmune disease causing hyperfunction of the thyroid gland. The concentration of selenium is high in the thyroid gland and two important groups of enzymes within the thyroid are selenoproteins, that is, they depend on selenium. Selenium may have beneficial effects on autoimmune hypothyroidism and on Graves' orbitopathy, but the effects of selenium on Graves' hyperthyroidism is unknown. We hypothesize that adjuvant selenium may be beneficial in the treatment of Graves' hyperthyroidism. The objective is to investigate if selenium supplementation plus standard treatment with anti-thyroid drugs versus standard treatment with anti-thyroid drugs will lead to a decrease in anti-thyroid drug treatment failure (that is, failure to remain euthyroid, without further treatment, one year after cessation of anti-thyroid drug treatment), faster and longer lasting remission (that is, anti-thyroid drug treatment success), and improved quality of life in patients with Graves-hyperthyroidism. Methods and design The trial is an investigator-initiated, randomised, blinded, multicentre clinical trial. Inclusion criteria are: age 18 years or older; diagnosis of active Graves' hyperthyroidism within the last two months; and informed consent. Exclusion criteria are major co-morbidity; previous radioactive iodine treatment; ongoing anti-thyroid drug treatment for more than two months; treatment with immunomodulatory drugs; known allergy towards the components in the selenium and placebo pills; pregnancy or breast-feeding; and intake of selenium supplementation above 70 μg per day. We plan to include 492 participants, randomised (1:1) to two tablets of 100 μg selenium once daily for the 24 to 30 months intervention period versus two identical placebo tablets once daily. The primary outcome is the proportion of participants with anti-thyroid drug treatment failure (see above) at the end of the intervention period (24 to 30 months). Secondary outcomes are: thyroid-specific quality of life during the first year after randomisation; level of thyroid stimulating hormone-receptor antibodies at 18 months after randomisation and at the end of the intervention period (24 to 30 months); hyperthyroid symptoms during the first year after randomisation; eye symptoms during the first year after randomisation, and at the end of the intervention period (24 to 30 months); adverse reactions during the intervention period; and serious adverse events during the intervention period. Discussion It was of great importance to the initiators of this trial, that the results would be directly applicable to daily clinical practice. Therefore, it was designed as a pragmatic trial: the patients follow their usual treatment at their usual hospitals. In order to still collect high quality data on the clinical course and quality of life, an elaborate trial management system was designed to keep track of patient input, need for trial personnel input and action, and to collect data from medical chart systems. Meticulous follow-up on missing responses to the QoL measurements has been incorporated into the system, to minimise missing quality of life data. Monitoring of adverse reactions and events is achieved by thorough instruction of the participants, surveillance of patient-reported outcomes, and integration with national databases regarding hospitalizations. A very long intervention period was necessary, since patients are not considered in remission until one year after stopping anti-thyroid drugs. Usually, patients are treated for 12 to 18 months with anti-thyroid drugs, yielding a total intervention period of 24 to 30 months. Trial registration ClinicalTrials.gov: NCT01611896.