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

NCT04063540 | Recruiting Phase 2

• 1 other identifier: 16-API-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

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.

Conditions

Migraine With Aura

Keywords

migraine; aura; Amiloride; acid-sensing ion channel

Outcome Measures

Primary Outcomes (1)

• Number of attacks with aura, with or without headache.

  12 weeks

Secondary Outcomes (2)

• Number of days with migraine headache, with or without aura

  12 weeks

• Functional repercussion

  12 weeks

Study Arms (2)

placebo-amiloride

OTHER

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; Drug: Placebos

amiloride -placebo

OTHER

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; Drug: Placebos

Interventions

Amiloride DRUG

Treatment by Amiloride vs placebo in crossover

amiloride -placebo; placebo-amiloride

Placebos DRUG

Treatment by Amiloride vs placebo in crossover

amiloride -placebo; placebo-amiloride

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of migraine with aura code
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (5)

Hôpital Pierre Wertheimer

Bron, France

NOT YET RECRUITING

CHU Gabriel Montpied

Clermont-Ferrand, France

NOT YET RECRUITING

AP-HM

Marly, France

RECRUITING

CHU de Montpellier

Montpellier, France

RECRUITING

CHU de NICE

Nice, France

RECRUITING

Related Publications (3)

• 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.

  PMID: 24042483 BACKGROUND

• 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.

  PMID: 16450381 RESULT

• 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.

  PMID: 16611468 RESULT

MeSH Terms

Conditions

Migraine with Aura; Migraine Disorders; Epilepsy

Interventions

Amiloride

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michel LANTERI-MINET, Dr

  Centre Hospitalier Universitaire de Nice

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michel LANTERI-MINET, Dr

CONTACT

04 92 03 76 46; lanteri-minet.m@chu-nice.fr

sylvie ROMETTINO

CONTACT

romettino.s@chu-nice.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 21, 2019
• Study Start: August 11, 2020
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)