PArtial REbreathing for Migraine With Aura 1

NCT05546385 | Terminated Results

• 1 other identifier: RH-001
• Study Type: interventional
• Target: 142
• Locations: 2 countries
• Sites: 15

Brief Summary

A prospective, multi-centre, randomized, double-blind, sham-controlled, parallel-group, group-sequential study to investigate safety and effectiveness of the Rehaler partial rebreathing device, in adults suffering from migraine with aura

Conditions

Migraine With Aura

Outcome Measures

Primary Outcomes (1)

• Absence of Moderate or Severe Pain at 2 Hours (AMSP2)

  The percentage of attacks in which the participant reported absence of headache of moderate or severe intensity at 2 hours post-treatment initiation

  2 hours

Secondary Outcomes (12)

• Pain Freedom at 2 Hours (PF2)

  2 hours

• Freedom From Most Bothersome Symptom at 2 Hours (MBSF2)

  2 hours

• Sustained Pain Freedom at 24 Hours (SPF24)

  24 hours

• Headache Score at 2 Hours (HS2)

  2 hours

• Most Bothersome Symptom Score at 2 Hours (MBS2).

  2 hours

Study Arms (2)

Active device

ACTIVE COMPARATOR

Device: Partial Rebreathing Device

Sham device

PLACEBO COMPARATOR

Device: Sham breathing device

Interventions

Partial Rebreathing Device DEVICE

Partial Rebreathing Device

Active device

Sham breathing device DEVICE

Sham breathing device

Sham device

Eligibility Criteria

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

You may qualify if:

• Participant has migraine with typical aura (ICHD3 classification 1.2.1) with the additional criterion that historically in more than 75% of cases of aura a moderate or severe headache begins between 10 and 60 minutes after aura onset.
• Participant has had 3 or more migraine-with-aura attacks over the last six months.
• Participant is 18 to 65 years of age.
• Participant's age at onset of migraine with aura was less than 50 years.
• If participant is taking migraine prophylactic drugs, the dose must have been stable for three months or more.
• Participant agrees to withhold usual acute migraine medications until at least two hours after treatment with the study device.
• Participant does not plan to initiate new (and/or change existing) migraine prophylaxis medication for the duration of Stage 1 of the study.
• For female participants: is willing to use adequate contraception during study participation
• Participant owns a smartphone compatible with the ePRO study diary app.
• Participant agrees to use the study device as intended, comply with all study requirements including treatment, follow-up visits, and recording required study data in the ePRO app.
• Participant is willing and able to provide written informed consent.

You may not qualify if:

• Participant has a history of chronic pulmonary disease (e.g. Chronic Obstructive Pulmonary Disease (COPD) or pulmonary fibrosis).
• Participant has a history of severe cardiovascular disease (e.g. symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure) or cerebrovascular disease (e.g. prior stroke or transient ischemic attack, symptomatic carotid artery disease, prior carotid endarterectomy or other vascular neck surgery).
• Participant has a history of intracranial hyper/hypo-tension.
• Participant has a history of cerebral aneurysm.
• Participant has had previous brain surgery, including stenting.
• Anaemia, defined as a hemoglobin concentration in capillary blood lower than 11g/dL
• Participant has a baseline SPO2 level which is lower than 95% performed at Site Visit 1.
• Participant has 15 or more headache days per month
• Participant has medication-overuse headache (ICHD3 classification 8.2).
• Participant has a known history or suspicion of recurring secondary headache which in the opinion of the investigator may interfere with the study.
• Hemiplegic migraine
• Participant has other significant and relevant pain problem (e.g. cancer pain, fibromyalgia or other head or facial pain disorders)
• Participant has a known history or suspicion of substance abuse or addiction (within the last 5 years) that in the opinion of the investigator may confound the study assessments.
• Participant has a history of psychiatric or cognitive disorder and/or behavioural problems which in the opinion of the investigator may interfere with the study.
• Participant belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with the follow-up requirements, or provide self-assessments is compromised (e.g. homeless, developmentally disabled, prisoner).

Sponsors & Collaborators

• Rehaler: lead
• Qmed Consulting A/S: collaborator

Study Sites (15)

Stanford University - Stanford Headache Clinic

Palo Alto, California, 94304, United States

Location

Profound Research-Southern California Neurology Consultants

Pasadena, California, 91105, United States

Location

Artemis Institute for Clinical Research

Riverside, California, 92503, United States

Location

Yale University

New Haven, Connecticut, 06519, United States

Location

MedStar Health Research Institute

Washington D.C., District of Columbia, 20010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

PharmaSite Research

Baltimore, Maryland, 21208, United States

Location

Clinvest Research

Springfield, Missouri, 65807, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 33136, United States

Location

Charité University Hospital

Berlin, 10117, Germany

Location

Essen University Hospital-West German Headache Center

Essen, 45147, Germany

Location

Frankfurt Headache Center

Frankfurt, 65929, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Jena University Hospital

Jena, 07747, Germany

Location

Munich University Hospital

Munich, 80336, Germany

Location

Related Publications (1)

• Gaul C, Ferreira S, Johansen T. Partial rebreathing is not effective for early treatment of migraine with aura attacks: Results of a double-blind, randomized, controlled trial (PAREMA1). Headache. 2025 Nov 21. doi: 10.1111/head.15090. Online ahead of print.

  PMID: 41272403 DERIVED

MeSH Terms

Conditions

Migraine with Aura

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Troels Johansen
• Organization: Rehaler A/S

tj@rehaler.com

004540977313

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sham device
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, multi-centre, randomized, double-blind, sham-controlled, parallel-group, group-sequential study

Study Record Dates

• First Submitted: September 14, 2022
• First Posted: September 19, 2022
• Study Start: August 8, 2023
• Primary Completion: October 30, 2024
• Study Completion: October 30, 2024
• Last Updated: March 25, 2025
• Results First Posted: March 25, 2025

Record last verified: 2025-03

Locations

DE (6); US (9)