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

Centre Hospitalier Universitaire de Nice

Status and phase: Enrolling; Phase 2

Conditions: Migraine With Aura

Treatments: Drug: Placebos; Drug: Amiloride

Study type: Interventional

Funder types: Other

Identifiers

NCT04063540

16-API-01

Details and patient eligibility

About

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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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40 participants in 2 patient groups

placebo-amiloride

Other group

Description:

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.

Treatment:

Drug: Amiloride

Drug: Placebos

amiloride -placebo

Other group

Description:

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.

Treatment:

Drug: Amiloride

Drug: Placebos