PArtial REbreathing for Migraine With Aura 1

Study Overview
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Brief Summary
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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

Official Title
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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
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Migraine With Aura

Intervention / Treatment
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* Device: Partial Rebreathing Device
* Device: Sham breathing device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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, or receive nerve blocks, injections or neurostimulation for migraine prophylaxis 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. Exclusion Criteria: 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). 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, multi-centre, randomized, double-blind, sham-controlled, parallel-group, group-sequential study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active device<br> | Device: Partial Rebreathing Device<br>* Partial Rebreathing Device<br>|
| Placebo Comparator: Sham device<br> | Device: Sham breathing device<br>* Sham breathing device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absence of moderate or severe pain at 2 hours (AMSP2) | The proportion 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 proportion of attacks with absence of headache pain two hours after treatment initiation | 2 hours | 
| Freedom from Most Bothersome Symptom at 2 hours (MBSF2) | The proportion of attacks with absence of MBS two hours after treatment initiation | 2 hours | 
| Sustained Pain Freedom at 24 hours (SPF24) | The proportion 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 (four-point scale) | 2 hours | 
| Most Bothersome Symptom Score at 2 hours (MBS2) | Most Bothersome Symptom score two hours after treatment initiation (four-point scale) | 2 hours | 
| Functional Disability Score at 2 hours (FDS2) | Functional Disability Score two hours after treatment initiation (four-point scale) | 2 hours | 
| Attacks with use of rescue medication from the 2 hours' time point until 24 hours (Res24) | The proportion 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 global impression of acute treatment effect on attack, evaluated at 48 hours after treatment initiation (5 point scale: 5 = Satisfied, 4 = Partially Satisfied, 3 = Neutral, 2 = Partially Unsatisfied, 1 = Unsatisfied) | 48 hours | 
| Light Sensitivity Score at 2 hours (LSS2) | Photophobia score two hours after treatment initiation (four-point scale) | 2 hours | 
| Nausea Score at 2 hours (NS2) | Nausea Score two hours after treatment initiation (four-point scale) | 2 hours | 
| Sound Sensitivity Score at 2 hours (SSS2) | Phonophobia score two hours after treatment initiation (four-point scale) | 2 hours | 
| Freedom from Relapse at 48 hours (FR48) | The proportion 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 |