TCDS for the Treatment of Chronic Migraine

This study is being performed in patients with chronic migraine (CM) which represents a significant burden to both individuals, but also the healthcare system and wider economy. Pharmacological options for the treatment of migraine have expanded in recent years, however, these are not infrequently associated with side effects and are not always effective for all patients. There is an increased need for non-pharmacological treatments such as neuromodulation. Furthermore, non-invasive neuromodulation is relatively safe and, in the case of the Nettle device, can be used at home after a single training session, potentially reducing the burden on healthcare services and increasing patients' autonomy with regards to their treatment.

Transcranial direct current stimulation (tDCS) is a form of non-invasive neuromodulation for which there is an increasing body of evidence in a number of fields including major psychiatric disorders, Parkinson's disease, post-stroke rehabilitation and epilepsy.12,13 The Nettle device, manufactured by Samphire Neuroscience, contains four electrodes, two of which provide stimulation to the primary motor cortex (M1), and two stimulate the dorsolateral prefrontal cortex (DLPFC). A treatment session consists of 2mA stimulation for 20 minutes per day. Nettle is a Class IIa medical device which has a CE mark and is currently marketed for use in dysmenorrhoea and the mood component of premenstrual syndrome. The proposed study would be the first to use Nettle in chronic migraine, therefore a small feasibility study is planned.

The research question is as follows: Is a randomised controlled trial of 12 weeks concurrent M1 and DLPFC tDCS (using the Nettle device) feasible in patients with chronic migraine, with specific regard to recruitment, adherence and monitoring?

The primary objective is: To assess the feasibility of home-based self-administration of tDCS for the preventative treatment of chronic migraine by evaluating recruitment rate, treatment adherence and diary data completeness

The secondary objectives are:

• To generate preliminary estimates of clinical effect size
• To assess tolerability and usability of the Nettle device
• To characterise the safety profile of the Nettle device

The progression criteria are as follows:

• Green (all primary feasibility endpoints met): proceed to definitive randomised controlled trial (RCT) if:
• Recruitment rate >1 participants per site per month AND
• Adherence rate ≥75% of schedule tDCS sessions completed AND
• Diary data completeness >80% of treatment phase days recorded.
• Amber (exactly one primary feasibility endpoint partially met, as defined below): review and refine study processes (e.g. recruitment material, device training, follow up procedures, data-capture methods) and consider repeating feasibility assessment if necessary before proceeding to RCT, if:
• Recruitment rate 0.8-1.0 participants per site per month
• Adherence rate 60-75% of scheduled tDCS sessions completed
• Diary data completeness 65-80% of treatment phase days recorded
• Red (two or more primary feasibility end points unmet, as defined below): halt progression and undertake significant protocol redesign before further feasibility testing
• Recruitment rate <0.8 participants per site per month
• Adherence rate <60% of scheduled tDCS sessions completed
• Diary data completeness <65% of treatment phase days recorded

This is an open label, single arm feasibility study which will be carried out at a single centre. The patients will be primarily recruited from the headache clinic at UCL Queen Square Institute of Neurology. This is expected to generate an ample number of suitable candidates, however additional patients may be recruited from the private headache clinic or via advertisements in migraine charities or support groups.

Appointment one is a virtual appointment to carry out screening (including collecting baseline data as detailed in 7.3.1), electronic written informed consent, carry out quality of life, anxiety and depression questionnaires and to give the patient the headache diary/assist with downloading the Headache Pro App to complete for the following month. If patients are unable to carry out this appointment virtually, they can be offered a face-to-face visit. The virtual or face to face appointment will be carried out by the sub-investigator.

Appointment two is a face-to-face appointment, at least four weeks after the screening appointment at the Queen Square Private Consulting Rooms with the sub-investigator. This visit marks the start of the treatment phase. The following activities are carried out:

• Review of written informed consent and eligibility criteria
• Review of Headache Pro App or paper diary
• Downloading of Nettle App (a representative from Samphire may attend to help troubleshoot)
• Demonstration of the device and explanation of its daily use
• Arrange time and date for final follow up Appointment three is a telephone call from the sub-investigator, one week into the treatment phase, to ensure participants are able to use the device correctly and are completing the diary. For participants using the Headache Pro App, data can be reviewed remotely by the chief investigator. Adverse events are recorded.

Appointment four is a face to face, or virtual visit, three months after the commencement of the treatment phase. The sub-investigator will repeat the quality of life and anxiety and depression questionnaires, ensure headache diaries are completed and review for any adverse events. Adherence will be reviewed (completed sessions are visible on the Samphire App). The patient satisfaction survey is completed at this visit.

Participants are encouraged to contact the sub-investigator between visits, should they develop adverse events, device malfunction, new medication problems which may affect eligibility or any other concern.