Efficacy of Amiloride Hydrochloride Dihydrate in Prophylaxis of Migraine with Aura: A Proof-of-Concept Study

The primary objective of this study is to evaluate the **efficacy** of amiloride, a non-specific ASIC-1 channel blocker, in the prophylaxis of **migraine aura**. This is clinically relevant as migraine with aura can significantly impact the quality of life, and effective prophylactic treatments are essential for reducing the frequency and severity of these episodes.

Secondary objectives include:

• Evaluating the efficacy of amiloride in migraine headache prophylaxis.
• Assessing the efficacy of amiloride by measuring functional impact in the prophylaxis of migraine with aura.
• Evaluating the efficacy of amiloride by measuring emotional impact in the prophylaxis of migraine with aura.
• Assessing the efficacy of amiloride by evaluating health status in the prophylaxis of migraine with aura.
• Evaluating the safety of amiloride in the prophylaxis of migraine with aura.

The clinical trial focuses on evaluating the efficacy of **amiloride** in the prophylaxis of **migraines with aura**. The study population comprises both male and female participants aged between 18 and 80 years. Participants are required to have a diagnosis of migraine with aura, specifically coded as 1.2.1 according to ICHD-3, and must have experienced at least one attack with aura per month in the three months preceding inclusion. The trial excludes individuals who have been on prophylactic antimigraine treatment within the month prior to the study. Women of childbearing age are required to use a reliable contraceptive method for at least three months before and one month after the study. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants must be affiliated with social security and have signed a written informed consent. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **amiloride hydrochloride dihydrate** in the prophylaxis of **migraines with aura**. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, thus minimizing bias. The trial is expected to span from August 11, 2020, to December 11, 2025, with participant involvement lasting up to three months. The study will include an initial screening visit, multiple follow-up visits, and a final end-of-study visit to assess the primary and secondary endpoints.

Participants will be screened based on specific inclusion criteria, such as being aged 18 to 80, having a diagnosis of migraine with aura according to ICHD-3, and experiencing at least one attack with aura per month in the three months prior to inclusion. The absence of prophylactic antimigraine treatment for at least one month before inclusion is also required. Women of childbearing age must use reliable contraception. The primary endpoint is the number of seizures with aura, while secondary endpoints include the number of days with migraine headache, functional and emotional impact scores, health status, and the occurrence of adverse events.

Study visits will be structured as follows: the inclusion visit will confirm eligibility and obtain informed consent. Follow-up visits will monitor the frequency and severity of migraine attacks, adherence to the treatment regimen, and any adverse events. The end-of-study visit will evaluate the overall efficacy and safety of the treatment. Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with the study protocol, or choose to withdraw consent. The trial aims to provide valuable insights into the potential of amiloride as a prophylactic treatment for migraines with aura.

The clinical trial involves the administration of **MODAMIDE 5 mg, comprimé**, which contains the active substance **amiloride hydrochloride dihydrate**. This experimental medication is presented in tablet form and is intended for oral administration. The dosage regimen specifies a maximum daily dose of 10 mg, with a total maximum dose of 900 mg over the course of the treatment. The treatment period is limited to a maximum of 3 months. The primary objective of the trial is to evaluate the efficacy of amiloride, a non-specific ASIC-1 channel blocker, in the prophylaxis of migraine aura. The pharmaceutical form of the medication is a tablet, and it is manufactured by SUBSTIPHARM. The medication is classified under the ATC code C03DB01, which corresponds to amiloride.

In addition to the experimental treatment, a **placebo** is utilized as a comparator in the study. The placebo is also administered in tablet form for oral use, ensuring that the administration route and form are consistent with the experimental medication. This allows for a controlled comparison of the efficacy of the active treatment against the placebo. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is designed to maintain rigorous standards of scientific inquiry, with all substances used being of chemical origin.

The clinical trial aims to assess the efficacy of **amiloride** in the prophylaxis of migraine aura. The primary endpoint for evaluating efficacy is the number of seizures with aura, with or without headache. Secondary endpoints include the number of days with migraine headache, with or without aura, the number of days with any type of headache, with or without aura, and the functional impact measured by the HIT-6 scale. Additionally, emotional impact will be assessed using the anxiety and depression scores on the HAD scale, and health status will be evaluated using the EQ-5D scale score. The occurrence or absence of significant or unknown adverse events will also be monitored.

Efficacy parameters will be collected and analyzed at specified timepoints throughout the trial. The use of validated scales such as HIT-6, HAD, and EQ-5D ensures the reliability and accuracy of the assessments. The trial is designed to provide a comprehensive evaluation of the impact of amiloride on migraine aura and associated symptoms, contributing valuable data to the understanding of its potential as a prophylactic treatment.