Selenium Supplementation in Youths With Autoimmune Thyroiditis

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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L-selenomethionine Supplementation in Children and Adolescents With Autoimmune Thyroiditis: a Randomized Blind Placebo-controlled Clinical Trial

Conditions
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Autoimmune Thyroiditis

Intervention / Treatment
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* Dietary Supplement: L-selenomethionine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-selenomethionine<br>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<br>* 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<br>|
| Placebo Comparator: Placebo<br>A group randomized to receive placebo (control group) for 6 months | Other: Placebo<br>* The group will be randomized to receive placebo (control group) for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in titer of thyroid autoantibodies (thyroid-peroxidase -AntiTPO-, and thyroglobulin -antiTg- antibodies) |  | 0,3,6,12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of serum selenium levels |  | 0 months | 
| 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. | 0,6,12 months | 
| Change in thyroxine dose per kg per day |  | 0,6,12 months | 
| Change in thyroid volume measured by ultrasonography |  | 0,6,12 months |