Clinical trial NCT02644707: Selenium Supplementation in Youths With Autoimmune Thyroiditis
Official title: L-selenomethionine Supplementation in Children and Adolescents With Autoimmune Thyroiditis: a Randomized Blind Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Autoimmune Thyroiditis
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
First posted: 2016-01-01
Enrollment: 100
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

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

Primary outcomes:
measure: Change in titer of thyroid autoantibodies (thyroid-peroxidase -AntiTPO-, and thyroglobulin -antiTg- antibodies)
timeFrame: 0,3,6,12 months
Secondary outcomes:
measure: Measurement of serum selenium levels
timeFrame: 0 months
measure: Change in state of thyroid function (Euthyroid or Hypothyroid)
timeFrame: 0,6,12 months
measure: Change in thyroxine dose per kg per day
timeFrame: 0,6,12 months
measure: Change in thyroid volume measured by ultrasonography
timeFrame: 0,6,12 months
Other outcomes:
Locations:
city: Thessaloniki
country: Greece
facility: Unit of Pediatric Endocrinology, Diabetes and Metabolism-4th Department of Pediatrics, Medical School of Aristotle University of Thessaloniki
Study officials:
affiliation: Unit of Pediatric Endocrinology, Diabetes and Metabolism - 4th Department of Pediatrics, Medical School of Aristotle University of Thessaloniki, 56403 Thessaloniki, Greece
name: Assimina Galli-Tsinopoulou, Assoc Prof
role: PRINCIPAL_INVESTIGATOR
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