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

Sponsor

Centre Hospitalier Universitaire de Nice (Other)

Overall Status

Unknown status

CT.gov ID

NCT04063540

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Migraine With Aura	Drug: Amiloride Drug: Placebos	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Nov 1, 2019

Anticipated Primary Completion Date :

Nov 1, 2019

Anticipated Study Completion Date :

Nov 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Other: placebo-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.	Drug: Amiloride Treatment by Amiloride vs placebo in crossover Drug: Placebos Treatment by Amiloride vs placebo in crossover
Other: amiloride -placebo 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 Treatment by Amiloride vs placebo in crossover Drug: Placebos Treatment by Amiloride vs placebo in crossover

Arm

Intervention/Treatment

Other: placebo-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.

Drug: Amiloride

Treatment by Amiloride vs placebo in crossover

Drug: Placebos

Treatment by Amiloride vs placebo in crossover

Other: amiloride -placebo

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

Treatment by Amiloride vs placebo in crossover

Drug: Placebos

Treatment by Amiloride vs placebo in crossover

Outcome Measures

Primary Outcome Measures

Number of attacks with aura, with or without headache. [12 weeks]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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