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

Phase 2

Recruiting

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
placebo-amiloride	Placebos	Patients will be treated for 12 weeks with placebo and then after a 4 week wash-out period, will be treated for 12 weeks with amiloride.
amiloride -placebo	Placebos	Patients will be treated for 12 weeks with amiloride and then after a 4 week wash-out period, will be treated for 12 weeks with placebo.
placebo-amiloride	Amiloride	Patients will be treated for 12 weeks with placebo and then after a 4 week wash-out period, will be treated for 12 weeks with amiloride.
amiloride -placebo	Amiloride	Patients will be treated for 12 weeks with amiloride and then after a 4 week wash-out period, will be treated for 12 weeks with placebo.

Primary Outcome Measures

Name	Time	Method
Number of attacks with aura, with or without headache.	12 weeks

Secondary Outcome Measures

Name	Time	Method
Functional repercussion	12 weeks	Anxiety and depression score on the Hospital Anxiety and Depression scale scale
Number of days with migraine headache, with or without aura	12 weeks

Locations (5): Hôpital Pierre Wertheimer
🇫🇷
Bron, France
CHU Gabriel Montpied
🇫🇷
Clermont-Ferrand, France
AP-HM
🇫🇷
Marly, France
CHU de Montpellier
🇫🇷
Montpellier, France
CHU de NICE
🇫🇷
Nice, France

Receive instant email notifications about changes in this clinical trial

Receive instant email notifications about changes in this clinical trial