OnabotulinumtoxinA blockade of the sphenopalatine ganglion in treatment-resistant chronic migraine (MiBlock): rationale, design and study protocol for a multi-centre, investigator initiated, randomised, quadruple-blinded placebo-controlled trial.

<ns3:p>Background Treatment-resistant chronic migraine patients constitute a heavily burdened patient population with need for novel treatment options. The sphenopalatine ganglion (SPG), located deep within the facial structures, is a synaptic junction in the trigemino-autonomic reflex that is hypothesised to play a part in migraine pathophysiology. A 2017 open-label pilot study explored the SPG as a target for onabotulinumtoxinA injections in chronic migraine using a navigation-guided injection device, demonstrating a favourable safety profile and promising response on migraine related efficacy outcomes. Methods MiBlock is a multi-centre, investigator-initiated, publicly funded, randomised, quadruple-blinded and placebo-controlled trial. Participation is voluntary and all participants must sign a written consent prior to inclusion. The study is approved by the Norwegian ethics committee and the Norwegian Medical Product Agency. Patients with treatment-resistant chronic migraine will be recruited from four Norwegian university hospitals until 170 have received study treatment. The study will investigate the efficacy of a single-session, bilateral, navigation-guided, percutaneous injection of either onabotulinumtoxinA (verum) or 0.9% NaCl (placebo) towards the SPG under local anaesthesia. The primary efficacy endpoint is the change from baseline in the frequency of moderate and severe headache days at weeks 5-8 post-injection. The primary efficacy outcome variable is collected prospectively through daily headache eDiary entries during the entire study participation. The treatment effect will be assessed by comparing the placebo and the treatment arm according to a prespecified statistical analysis plan. Discussion This trial addresses a novel treatment strategy in headache prevention. The study is designed to evaluate the efficacy and safety of onabotulinumtoxinA injection towards the SPG in chronic migraine, but results may shed light on the feasibility of navigation-guided SPG injections in several headache disorders. Results will be published in international open-access peer-reviewed journals. Trial registration number EudraCT number: 2018-004053-24. ClinicalTrial ref: NCT04069897. Protocol version 4.2, Date 21.11.2019</ns3:p>