Evaluation of Risedronate Sodium in Patients with Dilated Cardiomyopathy Due to Troponin T K210 Deletion Mutation

The primary objective of this study is to evaluate whether the administration of **Risedronate** 10 mg/day in patients with **dilated cardiomyopathy** due to K210 deletion mutation in the Troponin T gene is associated with a change in left ventricular function, as measured by echocardiogram. This is clinically relevant as it may provide insights into potential therapeutic benefits of Risedronate in improving cardiac function in this specific patient population.

Secondary objectives include assessing whether the administration of Risedronate 10 mg/day is associated with: - Improvement in functional capacity, measured in the stress test with consumption of oxygen. - Safety and tolerance in this population.

The clinical trial involves participants diagnosed with **dilated cardiomyopathy** due to the K210 deletion mutation in the Troponin T gene. The study population includes both male and female subjects, all of whom are older than 18 years. Participants are required to have a left ventricular ejection fraction (LVEF) of 50% or less. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. All participants have given written informed consent to partake in the study. The selection criteria ensure that the study population is representative of individuals with the specified genetic mutation and cardiac condition, without any specific lifestyle considerations such as diet or physical activity being highlighted.

The clinical trial is designed to evaluate the efficacy of **risedronate sodium** in patients with **dilated cardiomyopathy** due to a K210 deletion mutation in the Troponin T gene. This is a Phase 4, randomized, double-blind, controlled trial. The primary objective is to assess changes in left ventricular function, measured by echocardiography, after six months of treatment. Secondary endpoints include improvements in functional capacity, assessed through a stress test with oxygen consumption, also at six months. The trial is expected to commence recruitment on July 31, 2024, and conclude by July 31, 2026.

Participants will be involved in the study for a maximum of 12 months, with the treatment administered orally as a 10 mg daily dose of risedronate sodium. The study will begin with a screening visit to confirm eligibility, which includes criteria such as being over 18 years old, having a left ventricular ejection fraction (LVEF) of 50% or less, and providing written informed consent. Following the inclusion visit, participants will undergo regular follow-up visits to monitor their health status and treatment response. The end-of-study visit will occur at the conclusion of the treatment period, where final assessments will be conducted.

Participants may be withdrawn from the study if they experience adverse effects that compromise their safety, fail to adhere to the study protocol, or withdraw consent. The trial's design ensures that all participants and investigators remain blinded to the treatment allocation to maintain the integrity of the data collected. The study's findings will contribute to understanding the potential benefits of risedronate sodium in managing dilated cardiomyopathy associated with specific genetic mutations.

The clinical trial involves the administration of **Risedronate Sodium**, marketed under the name Actonel, in the form of **film-coated tablets**. Each tablet contains 5 mg of the active substance, Risedronate Sodium, which is a chemically derived compound. The pharmaceutical form is designed for **oral use**. The trial protocol specifies a dosage of 10 mg per day, which equates to two tablets daily. The maximum treatment period is set at 12 months, with a total cumulative dose not exceeding 3650 mg. The administration schedule is structured to ensure consistent daily intake, and participant compliance will be monitored through regular follow-ups and pill counts.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in this study. The focus is solely on evaluating the effects of Risedronate Sodium on patients with dilated cardiomyopathy due to a K210 deletion mutation in the Troponin T gene. The primary objective is to assess changes in left ventricular function, as measured by echocardiogram, following the administration of the experimental medication. The trial does not include any pediatric formulations, and the product is not classified as an orphan drug. The study is conducted under the authorization of Theramex Ireland Limited, with the product being relabeled for this specific clinical investigation.

Efficacy in the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the change in left ventricular ejection fraction (**LVEF**), which will be measured by echocardiography at 6 months. This parameter is crucial for determining the impact of Risedronate on cardiac function in patients with dilated cardiomyopathy due to the K210 deletion mutation in the Troponin T gene.

The secondary endpoint involves assessing improvement in functional capacity, which will be measured through a stress test evaluating oxygen consumption, also at the 6-month mark. These assessments will provide comprehensive insights into the efficacy of the treatment regimen. The trial is designed to monitor these parameters over a 12-month treatment period, ensuring a thorough evaluation of the therapeutic effects of Risedronate.