Stage 1 Registered Report:  Rationale, design and study protocol for a prospective, exploratory study Predicting Response to image-Guided Cryoneurolysis of the Greater Occipital Nerve (CryoGON) in Chronic Migraine Using a Conventional Greater Occipit

<ns3:p>Background Chronic migraine is frequently refractory to available preventive therapies. Image-guided cryoneurolysis of the greater occipital nerve (CryoGON) may provide longer-lasting relief than conventional greater occipital nerve (GON) blocks. This Stage 1 Registered Report describes a prospective, exploratory study evaluating whether response to a conventional GON block predicts subsequent response to CryoGON, and assesses open-label safety, tolerability, feasibility and efficacy of CryoGON. Methods The study is planned as a single-site, investigator-initiated, open-label clinical investigation. Adults with chronic migraine will complete a ≥28-day electronic baseline diary before receiving bilateral conventional GON blocks, followed by a ≥28-day observation. Eligible participants then undergo navigation-guided CryoGON with 12-week follow-up. The primary endpoint is the association between change in moderate-to-severe headache days after GON block (weeks 1–4) and after CryoGON (weeks 9–12). Key secondary endpoints estimate the diagnostic performance of GON-block response applying a ≥30% reduction threshold for treatment effect to identify CryoGON responders, including sensitivity, specificity and predictive values. Additional endpoints include change in migraine days, patient-reported global impression of change, Migraine-Specific Quality of Life Questionnaire v2.1, procedure tolerability, technical success, and safety (treatment-emergent adverse events and adverse device effects). Women of childbearing potential, including pregnant and breastfeeding participants, are eligible for participation. Discussion This study will provide the first systematic evaluation of whether a simple, widely available GON block can guide patient selection for CryoGON and will generate foundational open-label data on its clinical performance and safety. Findings will inform the design and justification of a subsequent sham-controlled trial. Trial registration and approvals The study will preregister at ClinicalTrials.gov. and obtain all necessary ethical approvals before study initiation. Sponsor: St. Olav’s University Hospital, Trondheim, Norway. Funding: Stiftelsen Dam (grant SDAM_FOR701626).</ns3:p>