This pilot, genotype-stratified clinical trial aims to evaluate the safety and preliminary efficacy of combined selenomethionine and myo-inositol supplementation in patients with autoimmune thyroiditis (AIT), including Hashimoto's thyroiditis, who carry the Thr92Ala (rs225014) variant in the DIO2 gene. The study will compare changes in thyroid function tests, autoantibody titers, and clinical symptoms between two cohorts: (1) carriers (homozygous or heterozygous) of the Thr92Ala variant and (2) individuals without this variant ("wild-type"). The hypothesis is that patients with the "unfavorable" DIO2 genotype will experience greater improvements in TSH levels, the free T3/ free T4 ratio, and autoimmunity markers when receiving selenomethionine plus myo-inositol, potentially due to enhanced support of thyroid hormone conversion and reduced autoimmune activity.
Rationale * The DIO2 gene encodes the type II iodothyronine deiodinase, which converts T4 (thyroxine) to the more active T3 (triiodothyronine) in peripheral tissues. * The Thr92Ala (rs225014) polymorphism may reduce enzyme activity, potentially leading to lower tissue T3 levels, even in patients with normal or slightly elevated T4 and TSH. * Selenium (as selenomethionine) supports the function of various selenoproteins, including deiodinases, and has been reported to reduce anti-thyroid antibody levels (particularly anti-TPO). * Myo-inositol has shown promise in modulating autoimmune and metabolic processes in thyroid disorders, possibly improving tissue sensitivity to thyroid hormones and reducing autoimmune inflammation. * A genotype-focused approach may reveal whether individuals carrying the DIO2 Thr92Ala variant derive a more substantial benefit from combined supplementation than those without the variant. 2. Study Goals * Primary Goal: To assess changes in TSH levels and the fT3/fT4 ratio over 12 weeks of combined selenomethionine and myo-inositol supplementation. * Secondary Goals: * To evaluate changes in thyroid autoantibody titers (anti-TPO, anti-Tg). * To assess thyroid ultrasound findings (vascularization, gland volume). * To measure improvements in patient-reported symptoms and quality of life using standardized questionnaires. * To determine the safety and tolerability of the combined intervention.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Selenomethionine (e.g., 100 µg/day) * Myo-inositol (e.g., 600 mg/day or higher) * Patients on levothyroxine will maintain their current dose (if clinically indicated).
Selenomethionine (e.g., 100 µg/day) * Myo-inositol (e.g., 600 mg/day or higher) * Patients on levothyroxine will maintain their current dose (if clinically indicated).
Center for New Medical Technologies
Novosibirsk, Russia
Change in Serum Thyroid-Stimulating Hormone (TSH) Concentration
Change in serum TSH concentration (reported in µIU/mL) from baseline to 16 weeks. The results will be presented as the mean change in concentration.
Time frame: 16 weeks
Change in Serum Free T3/Free T4 Ratio
Change in the ratio of serum free triiodothyronine (fT3) to free thyroxine (fT4) from baseline to 16 weeks. The outcome will be reported as the mean ratio change.
Time frame: 16 weeks
Change in Serum Anti-Thyroid Peroxidase (anti-TPO) Antibody Concentration
Change in the concentration of serum anti-thyroid peroxidase (anti-TPO) antibodies (measured in IU/mL) from baseline to 16 weeks. The outcome will be reported as the mean change in antibody concentration.
Time frame: 16 weeks
Change in Serum Anti-Thyroglobulin (anti-Tg) Antibody Concentration
Change in the concentration of serum anti-thyroglobulin (anti-Tg) antibodies (measured in IU/mL) from baseline to 16 weeks. The outcome will be reported as the mean change in antibody concentration.
Time frame: 16 weeks
Thyroid Gland Ultrasound Measurements: Volume
Ultrasound assessment of the thyroid gland will include measurement of thyroid volume (in mL) and qualitative assessment of thyroid echogenicity. Thyroid volume will be calculated using standardized ultrasound techniques, and echogenicity will be rated using a predetermined grading system.
Time frame: 12 weeks
Change in Patient-Reported Symptom Severity
Patient-reported symptom severity will be assessed using the Patient Health Questionnaire-15 \[PHQ-15\]). , if the PHQ-15, scores range from 0 to 30, with higher scores indicating worse symptom severity. The outcome will be reported as the mean change in symptom severity score from baseline to 12 weeks.
Time frame: 12 weeks
Number of incidence of any Treatment-Related Adverse Events
The incidence of treatment-related adverse events will be recorded and graded using the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Data will be reported as the number and percentage of participants experiencing one or more adverse events.
Time frame: 12 weeks
Change in Patient-Reported Quality of Life
Quality of life will be assessed using a validated instrument such as the World Health Organization Quality of Life-BREF (WHOQOL-BREF). For instance, scores for each domain range from 0 to 100, with higher scores indicating a better quality of life.
Time frame: 12 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.