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

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.

Study Overview

• Status: Recruiting
• Conditions: Migraine With Aura
• Intervention / Treatment: Drug: Amiloride; Drug: Placebos

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: sylvie ROMETTINO; Email: romettino.s@chu-nice.fr
• Study Contact Backup: Name: Michel LANTERI-MINET, Dr; Phone Number: 04 92 03 76 46; Email: lanteri-minet.m@chu-nice.fr

Study Locations

• France
  • Bron, France
    • Not yet recruiting
    • Hopital Pierre Wertheimer
    • Contact: Geneviève DEMARQUAY, Dr
  • Clermont-Ferrand, France
    • Not yet recruiting
    • CHU Gabriel MONTPIED
    • Contact: Xavier MOISSET, Dr
  • Marly, France
    • Recruiting
    • AP-HM
    • Contact: Anne DONNET, Dr
  • Montpellier, France
    • Recruiting
    • CHU de Montpellier
    • Contact: Anne DUCROS, Pr
  • Nice, France
    • Recruiting
    • CHU de Nice
    • Contact: Michel LANTERI-MINET, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Michel LANTERI-MINET, Dr, Centre Hospitalier Universitaire de Nice

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2020
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 19, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 21, 2019

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: migraine; Amiloride; aura; acid-sensing ion channel
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Migraine with Aura; Epilepsy; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Amiloride
• Other Study ID Numbers: 16-API-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No