Clinical trial NCT04063540: Acid-Sensing Ion Channel and Migraine Disease Proof of Concept Study on the Efficacy of Amiloride in the Prophylaxis of Migraine Aura
Official title: Acid-Sensing Ion Channel and Migraine Disease Proof of Concept Study on the Efficacy of Amiloride in the Prophylaxis of Migraine Aura
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Migraine With Aura
Keywords: migraine
aura
Amiloride
acid-sensing ion channel
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2019-08-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of attacks with aura, with or without headache.
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of days with migraine headache, with or without aura
timeFrame: 12 weeks
measure: Functional repercussion
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Bron
country: France
facility: Hôpital Pierre Wertheimer
city: Clermont-Ferrand
country: France
facility: CHU Gabriel Montpied
city: Marly
country: France
facility: AP-HM
city: Montpellier
country: France
facility: CHU de Montpellier
city: Nice
country: France
facility: CHU de NICE
Study officials:
affiliation: Centre Hospitalier Universitaire de Nice
name: Michel LANTERI-MINET, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.