PArtial REbreathing for Migraine With Aura 1 (PAREMA1)

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

Study Overview

• Status: Terminated
• Conditions: Migraine With Aura
• Intervention / Treatment: Device: Partial Rebreathing Device; Device: Sham breathing device

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite University Hospital
  • Essen, Germany, 45147
    • Essen University Hospital-West German Headache Center
  • Frankfurt, Germany, 65929
    • Frankfurt Headache Center
  • Freiburg, Germany, 79106
    • University Hospital Freiburg
  • Jena, Germany, 07747
    • Jena University Hospital
  • Munich, Germany, 80336
    • Munich University Hospital
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University - Stanford Headache Clinic
    • Pasadena, California, United States, 91105
      • Profound Research-Southern California Neurology Consultants
    • Riverside, California, United States, 92503
      • Artemis Institute for Clinical Research
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Health Research Institute
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • PharmaSite Research
  • Missouri
    • Springfield, Missouri, United States, 65807
      • Clinvest Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 33136
      • Thomas Jefferson University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Participant has had 3 or more migraine-with-aura attacks over the last six months.
3. Participant is 18 to 65 years of age.
4. Participant's age at onset of migraine with aura was less than 50 years.
5. If participant is taking migraine prophylactic drugs, the dose must have been stable for three months or more.
6. Participant agrees to withhold usual acute migraine medications until at least two hours after treatment with the study device.
7. Participant does not plan to initiate new (and/or change existing) migraine prophylaxis medication for the duration of Stage 1 of the study.
8. For female participants: is willing to use adequate contraception during study participation
9. Participant owns a smartphone compatible with the ePRO study diary app.
10. 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.
11. Participant is willing and able to provide written informed consent.

Exclusion Criteria:

1. Participant has a history of chronic pulmonary disease (e.g. Chronic Obstructive Pulmonary Disease (COPD) or pulmonary fibrosis).
2. 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).
3. Participant has a history of intracranial hyper/hypo-tension.
4. Participant has a history of cerebral aneurysm.
5. Participant has had previous brain surgery, including stenting.
6. Anaemia, defined as a hemoglobin concentration in capillary blood lower than 11g/dL
7. Participant has a baseline SPO2 level which is lower than 95% performed at Site Visit 1.
8. Participant has 15 or more headache days per month
9. Participant has medication-overuse headache (ICHD3 classification 8.2).
10. Participant has a known history or suspicion of recurring secondary headache which in the opinion of the investigator may interfere with the study.
11. Hemiplegic migraine
12. Participant has other significant and relevant pain problem (e.g. cancer pain, fibromyalgia or other head or facial pain disorders)
13. 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.
14. 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.
15. 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).
16. For female participants: is pregnant or actively trying to become pregnant.
17. Participant is participating in any other clinical investigation or has participated in an interventional clinical trial in the preceding 30 days.
18. Participant has any condition that according to the investigator may pose the participant at risk or provide confounding data.
19. Participant is unable, as perceived by study personnel, to correctly understand and follow the instructions for use of the device and ePRO app.
20. Sickle Cell Disease
21. 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active device	Device: Partial Rebreathing Device; Partial Rebreathing Device
Placebo Comparator: Sham device	Device: Sham breathing device; Sham breathing device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Freedom at 2 Hours (PF2)	The percentage of attacks with absence of headache pain two hours after treatment initiation	2 hours
Freedom From Most Bothersome Symptom at 2 Hours (MBSF2)	The percentage of attacks with absence of MBS two hours after treatment initiation	2 hours
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	24 hours
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.	2 hours
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.	2 hours
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.	2 hours
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)	24 hours
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)	48 hours
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.	2 hours
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.	2 hours
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.	2 hours
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	48 hours

Collaborators and Investigators

• Sponsor: Rehaler
• Collaborators: Qmed Consulting A/S

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2023
• Primary Completion (Actual): October 30, 2024
• Study Completion (Actual): October 30, 2024

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (Actual): September 19, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Migraine with Aura
• Other Study ID Numbers: RH-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No