Did you know that approximately 30% of migraine patients have Migraine-with-Aura where migraine attacks are preceded by a so-called aura, which can manifest as seeing flashes of light, blind spots in the field of vision, or tingling in the hands or face? Migraine-with-aura episodes can be debilitating, and studies have shown that three out of four migraine patients are not satisfied with their current treatment.

Researchers are exploring exciting new approaches – but they need your help! This study assesses the potential effects of a small, lightweight, and drug-free breathing device that delivers a mixture of CO2 and oxygen during the onset of aura symptoms. The study will investigate whether this new device is more effective than a placebo device in reducing headache, nausea, and other migraine symptoms.

• Men and women aged between 18 and 65
• Must have Migraine with Typical Aura
• Historically, in more than 75% of cases of aura, a moderate or severe headache begins between 10 and 60 minutes after aura onset.
• Fewer than 15 headache days per month
• Must have had 3 or more migraine-with-aura attacks within the last 6 months
• Must be willing to temporarily refrain from using usual migraine medication until at least 2 hours after the start of study treatment
• Preventive migraine medication must have been stable for at least 3 months
• Must not be planning to start a new or change existing migraine preventive medication
• Must not be in treatment with injections for migraine prevention (Botox, Aimovig/Erenumab, Ajovy/Fremanezumab, Emgality/Galcanezumab, Vyepti/Eptinezumab)
• Must have a smartphone compatible with the study diary app to record the required data
• Must not have previously had brain surgery, including stenting
• Must not have experienced paralysis of part of the body during the last hour before a headache starts
• Must be able to attend two study visits at the research site over approximately one year
• If you are unable to participate, consider sharing this study with someone who may benefit!

• Participants will receive a new potential treatment for treating migraines with aura at no cost.
• Participants may experience improvements in symptoms associated with episodes of Migraine with Aura.
• Participants will be contributing valuable information that may benefit those with migraines in the future.
• Participants will be helping to advance medical research.

• You can withdraw from the study at any time.
• Your information will be kept strictly confidential, except as required by law.
• Qualified health professionals will monitor your health as it relates to the study.

The study team will explain the research study in its entirety but some details are:

• The study has two Stages. In Stage 1, participants use either an active (“real”) device or a placebo (non-effective) device. Participants will not be told which device they are assigned to. In Stage 2, all participants use the active device.
• You will first be invited to visit the study clinic to find out if you are eligible for the study. At the visit, the study personnel will ask you questions about yourself, your headaches and your health. They will also take a small finger-prick blood sample to test the hemoglobin level in your blood. If you are a woman who is able to become pregnant you will also take a urine pregnancy test.
• If you are eligible to participate, you will be given a study kit with five devices to take home with you, with instructions for use. A video call will be scheduled where a study staff member will teach you how to use the study device and the smartphone app.
• When an aura starts, you must immediately start breathing through the study device. You should breathe through the device for as long as the aura lasts. You will also need to enter information about your symptoms in the app at regular intervals. You should refrain from using any other migraine medication until at least 2 hours after you started the study treatment.
• Participants will be in Stage 1 until four attacks have been treated or until the overall study ends.
• Afterward, you will be asked whether you wish to participate in Stage 2 where you will use up to five active (“real”) devices. Stage 2 lasts either until you have used all devices or until 12 months have passed.

Research Site: Medstar Health Research Institute
Location: Medstar Health Research Institute, 1420 Beverly Road, Suite 300, McLean, VA 22101
Lead Researcher: Dr. Jessica Ailani

This study has been reviewed by the Institutional Review Board Advarra.

Research Site: Stanford Headache Clinic
Location: Stanford Neuroscience Health Center, Room 4726, 213 Quarry Road, Palo Alto, CA 94304
Lead Researcher: Dr. Leon Moskatel

This study has been reviewed by the Stanford University Institutional Review Board.

Research Site: Thomas Jefferson University, Jefferson Headache Center
Location: 900 Walnut Street, Suite 200, Philadelphia, PA 19107, United States
Lead Researcher: Dr. Stephanie Nahas-Geiger

This study has been reviewed by the Advarra Institutional Review Board.

Research Site: Southern California Neurology Consultants
Location: 625 S. Fair Oaks Ave., Suite 325, Pasadena, CA 91105
Lead Researcher: Dr. Arbi Ohanian

This study has been reviewed by the Advarra Institutional Review Board.

Research Site: University of Miami
Location: 1120 NW 14th St Miami, FL 33136-2107
Lead Researcher: Dr. Teshamae Monteith

This study has been reviewed and approved by the University of Miami Institutional Review Board.

Research Site: Artemis Institute for Clinical Research
Location: 11748 Magnolia Ave, Suite D Riverside, CA 92503
Lead Researcher: Dr. Jack Vu

This study has been reviewed by the Advarra Institutional Review Board.

Research Site: PharmaSite Research
Location: 1314 Bedford Ave Ste 205 Pikesville, Maryland 21208
Lead Researcher: Dr. Dima Hnoosh

This study has been reviewed by the Advarra Institutional Review Board.