Study design
This study is an investigator-initiated clinical trial, investigating the effectiveness of the RhinoChill© intranasal cooling system for the acute relief of migraine in an adult population, through short periods of intranasal cooling.
We conducted a single-centre, prospective, open-label, observational, pilot study. Participants were enrolled from October 2013 to July 2014, from the outpatient clinics of the Neurology Department, Cumbria Partnership NHS Trust, and through a community engagement advertising campaign.
Study design consisted of a screening visit or phone call, baseline visit, minimum of one treatment and a follow-up phone call at 2 and 24 hours after each treatment. The principle of the intranasal cooling, procedure and safety aspects of the intervention were explained to each of the participants.
Patient recruitment
The study participants were otherwise healthy adults who met ICHD 2 diagnostic criteria for episodic migraine with or without aura, or chronic migraine and were capable of giving informed consent. Exclusion criteria included history of any current co-morbid illness or difficulty with insertion of the nasal cannula due to congenital anatomical narrowing of the nasal passages.
Trial device
The RhinoChill© Intranasal cooling device is a portable unit consisting of a control unit, a disposable nasal catheter and a 1-liter bottle of coolant. The device requires a supply of oxygen or medical air to drive the evaporation process of the coolant. The 10 cm long intranasal catheters have spray ports on the dorsal surface to distribute coolant into the nasal cavity, upwards towards the base of the skull (Figure 1).
The coolant used is perfluorohexane (PFH), a six-chain perfluorocarbon. PFH is a colorless, odourless, radiolucent liquid. PFH belongs to a class of perfluorocarbon fluids that are fully fluorinated with no functional reactive groups. They do not oxidize or hydrolyze and are thus chemically and biologically inert. They cannot undergo biological oxidation-reduction reactions to form reactive aldehydes, acid fluorides, radicals, or other acids. Since PFH does not react directly with biological tissue, they can form no reactive metabolites. PFH surface tension is lower than water so it will spread uniformly and quickly throughout the space in which it is sprayed. These properties facilitate RhinoChill coolant dispersion to the large diffuse surface area of the nasal cavity to maximize cooling.
Evaporation of the coolant provides rapid cooling to the nasal cavity of approximately 2°C, absorbing heat through evaporation and cooling local structures through direct conductive mechanisms and indirect haematogenous mechanisms. Safety of the device has been established in the cardiac arrest population where it has been used to induce rapid brain cooling for therapeutic hypothermia as neuroprotection [21, 22]. In this study, the device was only used on its lowest setting of ‘Low’ flow rate and for a maximum duration of 20 minutes as it was not the intention to induce therapeutic hypothermia.
Therapeutic regimen
This trial was a feasibility study. To ensure patient safety, participants attended the hospital Day Case Unit during a migraine attack, to obtain their treatment under medical supervision. At onset of a migraine attack, the patient would contact the trial researcher and come into the hospital for treatment. On arrival, baseline observations were taken including infrared tympanic thermometry, non-invasive blood pressure (NIBP), pulse and oxygen saturation. Migraine pain severity was assessed using a visual analogue scale (VAS, 0–10 with 0 being pain free and 10 very severe pain), which was extrapolated to provide a categorical scale of pain intensity using the Glaxo-scale of Severe, Moderate, Mild and None. The use of both scales allow for comparison with other published literature regarding non-pharmaceutical and pharmaceutical approaches to acute migraine treatment. The associated migraine symptoms (nausea, vomiting, photophobia, visual symptoms, face asymmetry, neck pain/stiffness and numbness/weakness in extremities) were also scored using VAS, whereby the patient provided a subjective composite score regarding the overall severity of their combined associated symptoms.
Following confirmation of an acute migraine attack, treatment was commenced. Lubricated nasal cannulae were inserted into both nostrils. If full insertion proved intolerable then a shallow insertion only (as far as tolerable - ¼, ½ or ¾ of the cannula) was completed. A maximum of 20 minutes of cooling was provided with predetermined early stoppage if there was full relief of pain or at the participant’s request due to discomfort.
Migraine pain severity score, tympanic thermometry and NIBP, as well as pain and discomfort associated with the cooling device, was measured every 5 minutes throughout the treatment. Immediately after treatment was terminated, 2 hours post treatment and at 24 hours after treatment, pain severity and migraine-associated symptom composite scores were recorded. The participants were required to stay within the unit for a minimum of 1 hour following their treatment as a safety precaution. The patient was then phoned at 2 hours to enable recording of a migraine pain and symptom severity score.
The primary endpoint for this study was the reduction of pain and associated symptoms from baseline assessment, just after the treatment, at 2 and 24 hours post-treatment. Secondary endpoints were tolerance to RhinoChill cooling during treatment, pain and discomfort levels due to the cooling procedure itself, and adverse events noted throughout the treatment phase and during follow up.
Statistical analyses
Data were analyzed using SPSS version 20.0 using paired sample T-test and the χ
2 test, where p < 0.05 would be considered significant. Shapiro-Wilks and Friedman’s non-parametric test were used to test the validity of the pain and symptom severity VAS scores.
Ethics or institutional review board approval
The study protocol was approved by the NRES Committee North West - Lancaster Ethics Committee. This study is registered at clinicaltrials.gov (NCT01898455). All participants provided written consent before taking part.
Study protocol
Trial registration: Clinicaltrials.gov registered trial, ClinicalTrials.gov Identifier: NCT01898455.