Intranasal Cooling for Symptomatic Relief of Migraine

This study is a multi centre, double blinded, randomized, prospective, parallel placebo controlled trial for demonstrating the effectiveness of the RhinoChill System for the symptomatic relief of migraine headache.

The specific study design consists of:

• Participant identification from neurology clinic records and gaining initial consent to transfer contact details to the trial team.
• Telephone contact or direct clinic contact with potential participants to describe the COOLHEAD 2 trial and to seek expressions of interest.
• Initial meetings with potential participants and discussion of trial, provision of patient information leaflets. Informed Consent taking.
• Initial 30 day prospective data collection period (minimum of 2 migraine attacks, longer period if needed)
• Randomisation to either placebo or active RhinoChill
• Device Delivery and training session for the use of the RhinoChill device, self administration, and record keeping.
• Treatment period for the treatment of 2 separate migraines with the RhinoChill.

During an initial screening visit or phonecall, the trial will be discussed with the potential participant and the inclusion/exclusion checklist will be completed.

If the patient meets all inclusion criteria and none of the exclusion criteria, they will be asked for permission to pass on contact details to a member of the trial team for further contact.

Arrangements will then be made for a meeting with the patient either at the clinic or in their own home to further discuss the trial and to consider enrolling into the study. At this time, they will be provided with a patient information sheet and will be shown the RhinoChill device. The patient will be given the opportunity to fully consider all aspects of participation in this trial and to discuss it with family members if they so wish before being being consented into the trial by a member of the study team.

At the time of consent, the researcher will also collect data for the baseline CRF and provide initial instruction on completion of the first stage data collection forms (further described below)

At the baseline visit, the patient will first be given the opportunity to ask any questions they may have about the research. A member of the research team will take informed consent and gain signatures on the consent form. Baseline data will then be collected, including history of migraine headache, frequency, severity of symptoms, medication and therapies currently ongoing or taken in the past. Base line vital signs will also be recorded at this time. Once completed, a short training session on completion of the prospective data collection forms for phase 1 of the trial will given and use of the supplied blood pressure machine and pulse oxymeter machine. Once the baseline visit has been completed the patient will begin a 30 day period of self data collection based on their migraine experience during that time frame and using data capture forms provided by the research nurse (a minimum of 2 migraine attacks are required, therefore if 2 have not occurred during the 30 days, further time will be given to allow the second migraine to occur).

If a patient has not had a single migraine in the first 30 days, then they will not be able to continue to the treatment phase as they have not met the inclusion criteria of at least 1 migraine per month. Following the conclusion to this initial period, the treatment phase will then begin.

After the end of the prospective data collection period, the patient will be randomised to either active treatment or placebo treatment. Randomisation will be provided by sealed envelopes held by E\&E CRO services (Vienna) who are also acting as independent monitors of the trial. Randomisation was performed via the online system www.sealedenvelope.com.

Training will be undertaken to ensure that the patient is fully competent and safe in the use of the RhinoChill intranasal cooling device.

The patient will be instructed on:

• Preparation of the device
• Insertion of the nasal catheter
• Selecting correct flow rate
• Positioning during treatment
• Cleaning and storage of the nasal catheters
• Trial documentation
• 24 hour contact numbers for additional supplies, troubleshooting and practical support.

The patient will also be left with a reference booklet for issues around the trial and the practical use of the RhinoChill device.

At the onset of migraine headache (or as soon as possible thereafter), the patient will start to complete the 'Treatment' CRF.

Each step of the treatment procedure is to be completed in order and as described to the patient. Patients are instructed that there is no scope for any alteration in the treatment order or requirements of the trial unless a safety issue becomes evident. If a patient does deviate from the standard procedures as outlined below, they are required to contact the 24 hour COOLHEAD 2 mobile phone to report the incident so that it can be reviewed and logged as a protocol deviation and reviewed by the site/principal investigator at the earliest opportunity. The RhinoChill device is then prepared for use and treatment can be administered.

The RhinoChill Migraine Intranasal catheters are then inserted and the 10 minute treatment is commenced on Low Flow. following these steps for each individual treatment:

It is recognised that participants in this study will already be taking medication for their migraine headache. Normal prophylaxis will be allowed as part of the trial and will be recorded in the initial screening interview. No change in prophylaxis is allowed within three months of the start of the trial or while the patient is participating in the trial.

However, acute treatments such as triptans are allowed to be taken but must be withheld until at least two hours following completion of treatment with the RhinoChill to allow assessment of the intervention. Any rescue medication taken after this point will be recorded in the associated trial documentation. A full medication history along with other therapies (including alternative therapies) will also be recorded.

No new treatment or therapy will start while the participant is enrolled in this trial.