A Study of Selenomethionine and Myo-inositol(SOLOWAYS_TM) in Patients With Autoimmune Thyroiditis Carrying the DIO2 Thr92Ala Polymorphism

A Pilot Study of Selenomethionine and Myo-inositol(SOLOWAYS_TM) in Patients With Autoimmune Thyroiditis Carrying the DIO2 Thr92Ala Polymorphism

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.

Study Overview

• Status: Completed
• Conditions: Autoimmune Thyroiditis
• Intervention / Treatment: Dietary supplement: Supplement groupx

Detailed Description

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
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Novosibirsk, Russian Federation, 630090
    • Center for New Medical Technologies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged 18-65 years with a clinical diagnosis of autoimmune thyroiditis (elevated anti- TPO and/or anti-Tg).
• TSH range consistent with subclinical hypothyroidism (e.g., TSH 4.5-10 mIU/L) or euthyroid status with AIT; patients on stable levothyroxine therapy are eligible if dose was unchanged for at least 6 weeks.
• Willingness to undergo genotyping for the DIO2 Thr92Ala variant. Confirmation of the Thr92Ala variant (homozygous or heterozygous) for Cohort A; absence of this variant for Cohort B.
• Ability to provide informed consent and comply with study procedures.

Exclusion Criteria:

• Overt hypothyroidism with TSH >10 mIU/L requiring immediate treatment adjustment.
• Significant comorbidities (e.g., uncompensated heart failure, severe renal or hepatic dysfunction, uncontrolled diabetes).
• Pregnancy or lactation (given potential changes in thyroid requirements and supplement safety considerations).
• Known hypersensitivity to selenium or inositol supplements.
• Severe psychiatric disorder interfering with protocol adherence.
• Concurrent use of high-dose selenium (>50 µg/day) or other thyroid-influencing nutraceuticals that cannot be discontinued prior to study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (Thr92Ala Carriers)	Dietary supplement: Supplement groupx; 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).
Experimental: Cohort B (Wild-Type DIO2)	Dietary supplement: Supplement groupx; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	12 weeks

Collaborators and Investigators

• Sponsor: S.LAB (SOLOWAYS)
• Collaborators: Center for New Medical Technologies, Novosibirsk, Russia

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2024
• Primary Completion (Actual): December 26, 2024
• Study Completion (Actual): February 21, 2025

Study Registration Dates

• First Submitted: February 20, 2025
• First Submitted That Met QC Criteria: March 4, 2025
• First Posted (Actual): March 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: genetics; supplements; Thyroid gland; T3; T4; anti-TPO
• Additional Relevant MeSH Terms: Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Thyroid Diseases; Hashimoto Disease; Thyroiditis; Thyroiditis, Autoimmune
• Other Study ID Numbers: SW022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No