Evaluation of Levothyroxine for TSH Suppression to Mitigate Radiation-Induced Hypothyroidism in Medulloblastoma and Pediatric Lymphoma Patients

The primary objective of this randomized study is to evaluate whether the incidence of **hypothyroidism** following radiation therapy in patients with **medulloblastoma**, **Hodgkin lymphoma**, and **non-Hodgkin lymphoma** can be reduced through the suppression of thyroid-stimulating hormone (TSH) during irradiation. This is clinically relevant as hypothyroidism is a common adverse effect of radiation therapy, which can significantly impact the quality of life and long-term health of patients. By potentially reducing the incidence of this condition, the study aims to improve patient outcomes and reduce the burden of post-treatment complications.

The secondary objective is to assess the number and type of parenchyma alterations after irradiation in all patients, encompassing both groups involved in the study. This evaluation will provide further insights into the tissue changes induced by radiation therapy, contributing to a better understanding of its effects and potential strategies for mitigation.

The clinical trial involves participants diagnosed with **Hodgkin and non-Hodgkin lymphoma** and **medulloblastoma**. The study population includes both male and female subjects, with an age range encompassing children, adolescents, and adults. Participants are required to be in general good health, specifically without previous primary or secondary hypothyroidism, and must provide written informed consent prior to any study-specific analysis or data collection. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria focus on patients who are at the stage of planning radiation therapy, including the thyroid parenchyma, and who have not yet undergone radiotherapy. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, double-blind, controlled study aimed at evaluating the efficacy of TSH suppression in reducing the incidence of hypothyroidism following radiation therapy in patients with **medulloblastoma**, **Hodgkin lymphoma**, and **non-Hodgkin lymphoma**. The trial will involve the administration of **levothyroxine** in tablet form, with a maximum daily dose of 2 µg/kg, over a treatment period of up to 14 days. The study is expected to run until December 28, 2029, with recruitment having commenced on December 13, 2021.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the principal inclusion criteria, which include the absence of previous primary or secondary hypothyroidism and the provision of written informed consent. Following the screening, participants will be randomized into treatment groups and will attend regular follow-up visits to monitor TSH levels and assess the onset of hypothyroidism. The primary endpoint is hypothyroidism-free survival at three years post-radiotherapy, evaluated through TSH blood dosage. The end-of-study visit will conclude the participant's involvement, with data collection focusing on the primary endpoint.

The expected length of participant involvement is approximately three years, with conditions for early termination including withdrawal of consent or the occurrence of adverse events that compromise participant safety. The trial is categorized as a Phase III study, indicating its advanced stage in the clinical research process. The study's design ensures rigorous assessment of the intervention's efficacy while maintaining participant safety and data integrity.

The clinical trial involves the administration of **Levothyroxine**, marketed under the name Levotiroxina Teva 25 microgrammi compresse. This medication is provided in the form of a **tablet** and is intended for **oral use**. The active substance, **levothyroxine**, is of chemical origin and is utilized to achieve thyroid-stimulating hormone (TSH) suppression during radiation therapy. The dosage is calculated based on body weight, with a maximum daily dose of 2 micrograms per kilogram. The treatment period is limited to a maximum of 14 days. The administration schedule is designed to ensure optimal TSH suppression, which is hypothesized to reduce the incidence of hypothyroidism in patients undergoing radiation therapy for medulloblastoma, Hodgkin lymphoma, and non-Hodgkin lymphoma.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of Levothyroxine as the experimental intervention. Participant compliance with the dosing regimen is monitored throughout the trial to ensure adherence to the prescribed treatment protocol. The trial aims to evaluate the efficacy of TSH suppression in protecting against radiation-induced hypothyroidism in the specified patient population.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint of **hypothyroidism-free survival** at three years post-radiotherapy. This endpoint will be measured in patients with medulloblastoma, Hodgkin lymphoma, and non-Hodgkin lymphoma who undergo radiation therapy involving the thyroid site. The analysis will focus on the intention-to-treat population, comparing two treatment groups: those receiving radiotherapy alone and those receiving radiotherapy in combination with levothyroxine. The onset of hypothyroidism will be monitored through TSH blood dosage assessments conducted within three years from the start of radiotherapy. The primary endpoint aims to determine if TSH suppression during irradiation can reduce the incidence of hypothyroidism in these patients.