Acid-Sensing Ion Channel and Migraine Disease Proof of Concept Study on the Efficacy of Amiloride in the Prophylaxis of Migraine Aura

Обзор

Recent data suggest involvement of Acid-Sensing Ion Channel channels in the pathophysiology of migraine making these channels a therapeutic target of migraine disease. The implication of Acid-Sensing Ion Channels is discussed through Acid-Sensing Ion Channel-1 which is the most expressed Acid-Sensing Ion Channel channel subtype in the central nervous system. In a mouse model, cortical spreading depression is inhibited by different Acid-Sensing Ion Channel blockers including amiloride which is a non-selective blocker of the Acid-Sensing Ion Channel-1 channel. From a translational perspective, an efficacy of amiloride on a series of migraine patients suffering from severe aura in open conditions. The APAM study is a proof-of-concept study that aims to evaluate the effect of amiloride in the prophylaxis of migraine with aura. This is a randomized crossover study versus placebo conducted in 3 French headache centers.

Вмешательства

• Препарат Amiloride
  Treatment by Amiloride vs placebo in crossover
• Препарат Placebos
  Treatment by Amiloride vs placebo in crossover

Первичные конечные точки

• Number of attacks with aura, with or without headache. [Срок оценки: 12 weeks]

Вторичные конечные точки (2)

• Number of days with migraine headache, with or without aura [Срок оценки: 12 weeks]
• Functional repercussion [Срок оценки: 12 weeks]

Критерии участия

Критерии включения

• Diagnosis of migraine with aura code
• At least 1 aura with aura per month in the 3 months prior to inclusion
• No prophylactic antimigraine treatment for at least 1 month prior to inclusion
• For women of childbearing age, use of a reliable contraceptive method at least 3 months before and 1 month after the study
• Signature of written informed consent
• Patient affiliated with Social Security

Критерии исключения

• Existence of contraindication to taking amiloride:

• Known hypersensitivity to the molecule
• Hyperkalemia (potassium level (> 5.5 mmol / l))
• Use of another hyperkalemic diuretic or potassium salts
• Renal insufficiency (clearance <60 ml / min)
• Severe hepatocellular insufficiency
• In combination with lithium, converting enzyme inhibitors, angiotensin II inhibitors (except if there is hypokalemia), ciclosporin, tacrolimus, non-antiarrhythmic drugs giving torsades de pointes
• Cardiovascular and renal history, for subjects over 75 years old
• Patient, who from an investigator's point of view would not be compliant to the procedure of the study
• Pregnant or lactating patient
• Patient under trusteeship, under guardianship, protected by law

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Франция · 5 центров

• Hôpital Pierre Wertheimer — Bron
• CHU Gabriel Montpied — Clermont-Ferrand
• AP-HM — Marly
• CHU de Montpellier — Montpellier
• CHU de NICE — Nice

Публикации

• Charles AC, Baca SM. Cortical spreading depression and migraine. Nat Rev Neurol. 2013 Nov;9(11):637-44. doi: 10.1038/nrneurol.2013.192. Epub 2013 Sep 17. PMID 24042483
• Ayata C, Jin H, Kudo C, Dalkara T, Moskowitz MA. Suppression of cortical spreading depression in migraine prophylaxis. Ann Neurol. 2006 Apr;59(4):652-61. doi: 10.1002/ana.20778. PMID 16450381
• Ligthart L, Boomsma DI, Martin NG, Stubbe JH, Nyholt DR. Migraine with aura and migraine without aura are not distinct entities: further evidence from a large Dutch population study. Twin Res Hum Genet. 2006 Feb;9(1):54-63. doi: 10.1375/183242706776403019. PMID 16611468

Идентификаторы

NCT: NCT04063540 · 16-API-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗