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

Study Overview
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Brief Summary
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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.

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

Conditions
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Migraine With Aura

Intervention / Treatment
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* Drug: Amiloride
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: placebo-amiloride<br>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. | Drug: Amiloride<br>* Treatment by Amiloride vs placebo in crossover<br>Drug: Placebos<br>* Treatment by Amiloride vs placebo in crossover<br>|
| Other: amiloride -placebo<br>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. | Drug: Amiloride<br>* Treatment by Amiloride vs placebo in crossover<br>Drug: Placebos<br>* Treatment by Amiloride vs placebo in crossover<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of attacks with aura, with or without headache. |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of days with migraine headache, with or without aura |  | 12 weeks | 
| Functional repercussion | Anxiety and depression score on the Hospital Anxiety and Depression scale scale | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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migraine, aura, Amiloride, acid-sensing ion channel