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CompletedNCT02644707THYROSELUpdated Feb 5, 2020

Selenium Supplementation in Youths With Autoimmune Thyroiditis

A Phase 4 interventional study of L-selenomethionine and Placebo in Autoimmune Thyroiditis, sponsored by Aristotle University Of Thessaloniki. Completed at 1 site in Greece. Open to participants aged 4 Years to 18 Years. Per ClinicalTrials.gov, last updated 2020-02-05.

Sponsored by Aristotle University Of Thessaloniki · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
100
Allocation
Randomized
Ages
4 Years to 18 Years
Sex
All
01

Study summary

To investigate whether the supplementation of organic selenium at the "adult" dose (200 mcg per day in the form of L-selenomethionine) has a favorable impact on thyroid function, including the titer of anti-thyroid antibodies [Anti-thyroid peroxidase (anti-TPO) and Anti-thyroglobulin (anti-Tg) antibodies], in children and adolescents with autoimmune thyroiditis (AT).

Read the detailed description

Background: Selenium in the form of seleno-cysteine is an essential component of enzymes that remove toxic substances from the body, such as glutathione peroxidase (GPX) in thyroid cells as well as seleno-dependent iodothyronine deiodinase that catalyses extra-thyroidal production of triiodothyronine (T3). In general, selenium deficiency may influence production of free radicals, conversion of thyroxine T4 to T3, cytokine production and immune mechanisms. Thus, it has been previously suggested that its supplementation may have a beneficial effect in patients with autoimmune thyroiditis, especially in those with increased inflammatory activity and a higher antibody titer. Although the two studies that have so far been conducted in pediatric populations demonstrated no significant effect of selenium administration on the titre of antibodies, the researchers did administer selenium either in the form of inorganic sodium selenite at the "adult" dose (100-200 mcg daily) or in the form of organic L-selenomethionine at the reduced dose (50 mcg daily). Therefore, to the best of our knowledge, selenium supplementation in the form of organic L-selenomethionine at the "adult" dose (200 mcg daily) has not been investigated in children and adolescents with autoimmune thyroiditis (AT) so far.

Objective: Our aim is to investigate whether the supplementation of organic selenium at the "adult" dose (200 mcg per day in the form of L-selenomethionine) has a favorable impact on thyroid function, including the titer of anti-thyroid antibodies (thyroid-peroxidase antiTPO, and thyroglobulin -antiTg- antibodies), in children and adolescents with autoimmune thyroiditis (AT).

Design and Methods: This is a randomized blinded placebo-controlled clinical trial of selenium supplementation versus placebo in children and adolescents with autoimmune thyroiditis (AT). The trial will include 100 consecutive participants (50 participants in each arm) from the Unit of Pediatric Endocrinology of the 4th Department of Pediatrics, Medical School, Aristotle University of Thessaloniki, Greece. The patients will be informed and given their written consent to be included in the study. The subjects will then be randomized to receive either organic selenium in the form of L-selenomethionine at the dose of 200mcg daily (intervention group) or placebo (control group) for 6 months. Both groups will receive oral tablets (one daily), which will be identical in appearance, taste and smell and will differ only in the type of active substance (L-selenomethionine or placebo). Six months of additional follow-up will lead to trial duration of 12 months. The experimental supplement will be given by the Pharmaceutical company marketing the product SEMED200® (INTERMED Pharmaceutical Laboratories). In all participants, determination of the concentrations of thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibody (TgAb) will be made at four times (0, 3, 6 and 12 months). Thyroid volume and morphology will also be sonographically evaluated in three times (0, 6 and 12 months). Serum selenium levels in the form of selenomethionine will also be determined once (at the beginning of the study).

Time-schedule: January- February 2015: protocol preparation. March 2015: first participant's first visit. March 2016: last participant's first visit. September 2016: last participant's last visit. September - October 2016: analysis of biological samples and data, preparation of manuscripts, March 2017: last participant's completion of follow-up.

02

Conditions studied

03

Who can participate

Ages eligible
4 Years to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria: A positive titer of antithyroid peroxidase (anti-TPO) or antithyroglobulin (anti-Tg) antibodies (TPO and / or Tg> 60 IU / ml) and at least one of:

  • Abnormal thyroid function that requires substitution treatment with L-thyroxine (TSH > 5 micro-units per milliliter (mcU/ml) and decreased or normal levels of fT4 or fT3)
  • Increased volume of thyroid gland (goiter)
  • Morphological changes on ultrasound of the thyroid gland

Exclusion Criteria:

  • Presence of another chronic disease or autoimmune disease or being under medication
  • Age of diagnosis above 18 years
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
100 participants (actual)

Study arms

  • Experimental
    L-selenomethionine

    A group randomized to receive organic selenium in the form of L-selenomethionine at the dose of 200mcg daily (intervention group) for 6 months

    Dietary Supplement: L-selenomethionine

  • Placebo comparator
    Placebo

    A group randomized to receive placebo (control group) for 6 months

    Other: Placebo

Interventions

  • Dietary supplementL-selenomethionine

    The group will be randomized to receive organic selenium in the form of L-selenomethionine at the dose of 200mcg daily (intervention group) for 6 months

  • OtherPlacebo

    The group will be randomized to receive placebo (control group) for 6 months

05

What researchers measure

Primary outcomes

  1. Change in titer of thyroid autoantibodies (thyroid-peroxidase -AntiTPO-, and thyroglobulin -antiTg- antibodies)

    Time frame: 0,3,6,12 months

Secondary outcomes

  1. Measurement of serum selenium levels

    Time frame: 0 months

  2. Change in state of thyroid function (Euthyroid or Hypothyroid)

    Hypothyroid state will be defined as the state of abnormal thyroid function that requires substitution treatment with L-thyroxine; in particular, if thyroid-stimulating hormone (TSH) serum levels are greater than 5 micro-units per milliliter (mcU/ml) and/or the levels of fT4 or fT3 are decreased. Otherwise the state will be considered as euthyroid.

    Time frame: 0,6,12 months

  3. Change in thyroxine dose per kg per day

    Time frame: 0,6,12 months

  4. Change in thyroid volume measured by ultrasonography

    Time frame: 0,6,12 months

06

Study locations

1 site
  • Unit of Pediatric Endocrinology, Diabetes and Metabolism-4th Department of Pediatrics, Medical School of Aristotle University of Thessaloniki
    Thessaloniki, 56403, Greece
07

References and documents

Publications

  • 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 Jan;18(1):7-12. doi: 10.1089/thy.2007.0127. PubMed 18302514 ↗
  • Anastasilakis AD, Toulis KA, Nisianakis P, Goulis DG, Kampas L, Valeri RM, Oikonomou D, Tzellos TG, Delaroudis S. Selenomethionine treatment in patients with autoimmune thyroiditis: a prospective, quasi-randomised trial. Int J Clin Pract. 2012 Apr;66(4):378-83. doi: 10.1111/j.1742-1241.2011.02879.x. Epub 2012 Feb 22. PubMed 22356267 ↗
  • Bonfig W, Gartner R, Schmidt H. Selenium supplementation does not decrease thyroid peroxidase antibody concentration in children and adolescents with autoimmune thyroiditis. ScientificWorldJournal. 2010 Jun 1;10:990-6. doi: 10.1100/tsw.2010.91. PubMed 20526530 ↗
  • Duntas LH, Mantzou E, Koutras DA. Effects of a six month treatment with selenomethionine in patients with autoimmune thyroiditis. Eur J Endocrinol. 2003 Apr;148(4):389-93. doi: 10.1530/eje.0.1480389. PubMed 12656658 ↗
  • Eskes SA, Endert E, Fliers E, Birnie E, Hollenbach B, Schomburg L, Kohrle J, Wiersinga WM. Selenite supplementation in euthyroid subjects with thyroid peroxidase antibodies. Clin Endocrinol (Oxf). 2014 Mar;80(3):444-51. doi: 10.1111/cen.12284. Epub 2013 Jul 31. PubMed 23844613 ↗
  • 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 Apr;87(4):1687-91. doi: 10.1210/jcem.87.4.8421. PubMed 11932302 ↗
  • Krysiak R, Okopien B. The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto's thyroiditis. J Clin Endocrinol Metab. 2011 Jul;96(7):2206-15. doi: 10.1210/jc.2010-2986. Epub 2011 Apr 20. PubMed 21508145 ↗
  • 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 Jul;17(7):609-12. doi: 10.1089/thy.2007.0040. PubMed 17696828 ↗
  • 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 Oct;73(4):535-9. doi: 10.1111/j.1365-2265.2009.03758.x. PubMed 20039895 ↗
  • Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab. 2007 Apr;92(4):1263-8. doi: 10.1210/jc.2006-1821. Epub 2007 Feb 6. PubMed 17284630 ↗
  • Onal H, Keskindemirci G, Adal E, Ersen A, Korkmaz O. Effects of selenium supplementation in the early stage of autoimmune thyroiditis in childhood: an open-label pilot study. J Pediatr Endocrinol Metab. 2012;25(7-8):639-44. doi: 10.1515/jpem-2012-0078. PubMed 23155687 ↗
  • Toulis KA, Anastasilakis AD, Tzellos TG, Goulis DG, Kouvelas D. Selenium supplementation in the treatment of Hashimoto's thyroiditis: a systematic review and a meta-analysis. Thyroid. 2010 Oct;20(10):1163-73. doi: 10.1089/thy.2009.0351. PubMed 20883174 ↗
  • Turker O, Kumanlioglu K, Karapolat I, Dogan I. Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses. J Endocrinol. 2006 Jul;190(1):151-6. doi: 10.1677/joe.1.06661. PubMed 16837619 ↗
  • van Zuuren EJ, Albusta AY, Fedorowicz Z, Carter B, Pijl H. Selenium supplementation for Hashimoto's thyroiditis. Cochrane Database Syst Rev. 2013 Jun 6;2013(6):CD010223. doi: 10.1002/14651858.CD010223.pub2. PubMed 23744563 ↗
  • Zhu L, Bai X, Teng WP, Shan ZY, Wang WW, Fan CL, Wang H, Zhang HM. [Effects of selenium supplementation on antibodies of autoimmune thyroiditis]. Zhonghua Yi Xue Za Zhi. 2012 Aug 28;92(32):2256-60. Chinese. PubMed 23158484 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT02644707
Lead sponsor
Aristotle University Of Thessaloniki
Responsible party
Assimina Galli-Tsinopoulou (ASSSOCIATE PROFESSOR, Aristotle University Of Thessaloniki) — Principal investigator
First posted
Jan 1, 2016
Start date
Aug 2014
Primary completion
Oct 2016
Completion
Aug 2018
Last update
Feb 5, 2020

Study contacts

Assimina Galli-Tsinopoulou, Assoc Prof
principal investigator · Unit of Pediatric Endocrinology, Diabetes and Metabolism - 4th Department of Pediatrics, Medical School of Aristotle University of Thessaloniki, 56403 Thessaloniki, Greece

Oversight

Data monitoring committee
No
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