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Migraine With AuraPAREMA1NCT05546385

PArtial REbreathing for Migraine With Aura 1

A study testing Partial Rebreathing Device in people with Migraine With Aura, run by Rehaler at 15 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Migraine With Aura
What is being tested?
Partial Rebreathing Device
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
142 participants
Where
15 sitesin 2 countries
Study dates
8 Aug 2023to 30 Oct 2024
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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).
  • For female participants: is pregnant or actively trying to become pregnant.
  • Participant is participating in any other clinical investigation or has participated in an interventional clinical trial in the preceding 30 days.
  • Participant has any condition that according to the investigator may pose the participant at risk or provide confounding data.
  • Participant is unable, as perceived by study personnel, to correctly understand and follow the instructions for use of the device and ePRO app.
  • Sickle Cell Disease
  • Participant is being treated with nerve blocks or injections for migraine prophylaxis on a regularly scheduled basis (including Botox, Aimovig/Erenumab, Ajovy/Fremanezumab, Emgality/Galcanezumab or Vyepti/Eptinezumab).

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States9 sites

  • PharmaSite Research

    Baltimore, Maryland, 21208

  • University of Miami

    Miami, Florida, 33136

  • Yale University

    New Haven, Connecticut, 06519

  • Stanford University - Stanford Headache Clinic

    Palo Alto, California, 94304

  • Profound Research-Southern California Neurology Consultants

    Pasadena, California, 91105

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 33136

  • Artemis Institute for Clinical Research

    Riverside, California, 92503

  • Clinvest Research

    Springfield, Missouri, 65807

  • MedStar Health Research Institute

    Washington D.C., District of Columbia, 20010

Other trials in United States

Germany6 sites

  • Charité University Hospital

    Berlin, 10117

  • Essen University Hospital-West German Headache Center

    Essen, 45147

  • Frankfurt Headache Center

    Frankfurt, 65929

  • University Hospital Freiburg

    Freiburg im Breisgau, 79106

  • Jena University Hospital

    Jena, 07747

  • Munich University Hospital

    Munich, 80336

Other trials in Germany

About this study

Official title: 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

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

Being tested
Partial Rebreathing Device, Sham breathing device
Medical subject headings
Migraine with Aura

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Partial Rebreathing DeviceDevice

    Partial Rebreathing Device

  • Sham breathing deviceDevice

    Sham breathing device

Study groups in NCT05546385
Study groupRoleWhat they receive
Active deviceActive comparatorNot described
Receives: Device: Partial Rebreathing Device
Sham devicePlacebo comparatorNot described
Receives: Device: Sham breathing device

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 2 hours

Secondary outcomes (12)

  1. Pain Freedom at 2 Hours (PF2)

    The percentage of attacks with absence of headache pain two hours after treatment initiation

    Measured: 2 hours

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

    The percentage of attacks with absence of MBS two hours after treatment initiation

    Measured: 2 hours

  3. Sustained Pain Freedom at 24 Hours (SPF24)

    The percentage of attacks having no headache pain at 2 hours after treatment initiation, with no use of rescue medication and no relapse of headache pain within 24 hours

    Measured: 24 hours

  4. Headache Score at 2 Hours (HS2)

    Headache Score 2 hours after treatment initiation. Measured on Likert four-point scale: 0 = no headache; 1 = mild headache; 2 = moderate headache; 3 = severe headache.

    Measured: 2 hours

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

    Most Bothersome Symptom score two hours after treatment initiation. Measured on Likert four-point scale: 0 = symptom absent; 1 = mild degree of symptom; 2 = moderate degree of symptom; 3 = severe degree of symptom.

    Measured: 2 hours

  6. Functional Disability Score at 2 Hours (FDS2)

    Functional Disability Score two hours after treatment initiation. Measured on Likert four-point scale: 0 = no functional disability; 1 = mild functional disability; 2 = moderate functional disability; 3 = severe functional disability.

    Measured: 2 hours

  7. Attacks With Use of Rescue Medication From the 2 Hours' Time Point Until 24 Hours (Res24)

    The percentage of attacks with use of rescue medication from the 2 hours' time point until 24 hours (Res24)

    Measured: 24 hours

  8. Participant Satisfaction at 48 Hours (PS48)

    Participant's overall satisfaction with the acute treatment effect on attack, evaluated at 48 hours after treatment initiation (5 point satisfaction scale: 5 = Satisfied, 4 = Partially Satisfied, 3 = Neutral, 2 = Partially Unsatisfied, 1 = Unsatisfied)

    Measured: 48 hours

  9. Light Sensitivity Score at 2 Hours (LSS2)

    Photophobia (light sensitivity) score two hours after treatment initiation. Measured on Likert four-point scale: 0 = no photophobia; 1 = mild photophobia; 2 = moderate photophobia; 3 = severe photophobia.

    Measured: 2 hours

  10. Nausea Score at 2 Hours (NS2)

    Nausea Score two hours after treatment initiation. Measured on Likert four-point scale: 0 = no nausea; 1 = mild nausea; 2 = moderate nausea; 3 = severe nausea.

    Measured: 2 hours

  11. Sound Sensitivity Score at 2 Hours (SSS2)

    Phonophobia (sound sensitivity) score two hours after treatment initiation. Measured on Likert four-point scale: 0 = no phonophobia; 1 = mild phonophobia; 2 = moderate phonophobia; 3 = severe phonophobia.

    Measured: 2 hours

  12. Freedom From Relapse at 48 Hours (FR48)

    The percentage of attacks having no headache pain at 2 hours after dose, with no use of rescue medication and no relapse of headache pain within 48 hours

    Measured: 48 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2022
  2. Study start8 Aug 2023
  3. Primary completion30 Oct 2024
  4. Study completion30 Oct 2024

Why it stopped: Interim analysis lack-of-effect stopping condition was met

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective, multi-centre, randomized, double-blind, sham-controlled, parallel-group, group-sequential study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
142 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05546385
Sponsor's protocol ID
RH-001
Acronym
PAREMA1
Status last verified
Mar 2025
First submitted
14 Sep 2022
Last updated
25 Mar 2025
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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. 2026 Feb;66(2):417-427. doi: 10.1111/head.15090. Epub 2025 Nov 21.

    PubMed 41272403

Questions about this trial

What is this clinical trial studying?

A study testing Partial Rebreathing Device in people with Migraine With Aura, run by Rehaler at 15 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absence of Moderate or Severe Pain at 2 Hours (AMSP2) (time frame: 2 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05546385, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2025.

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