A First-in-human Study to Assess the Initial Safety, Tolerability, and Effectiveness of the ONSS Bilateral Occipital Nerve Field Stimulation System for the Prophylactic Treatment of Chronic Cluster Headache in Difficult-to-treat Subjects.

Inclusion criteria

• ICHD-3 criteria for chronic cluster headache
• Documented history of CCH since at least 2 years
• Minimum mean attack frequency of 4 attacks per week at baseline (-4week to +2 week up to implant)
• Documented minimum 4 weeks of retrospective cluster headache diary data
• Age range: 22-70 years
• Difficult-to-treat CCH with documented previous complete failure, insufficient efficacy, intolerance, or contra-indications to most preventive CH treatments among which are oral steroids or suboccipital infiltrations, verapamil, lithium carbonate and topiramate.
• No preventive CH treatment or stable preventive CH medication for ≥ 2 weeks before enrolment.

Subject agrees not to change existing treatment during the whole duration of the trial.

• Participant written informed consent provided before enrolment
• Participant willing and capable of subjective evaluation and to fill in an electronic CH diary, to understand questionnaires, and to read, understand and sign the written informed consent form.
• Partcipant willing and able to comply with study-related requirements, procedures, and visits.

Exclusion criteria

• Other significant neurological, psychiatric, or disabling diseases which in the opinion of the investigator may interfere with the study.
• History of epilepsy, current treatment of epilepsy
• Documented history of cerebrovascular accident (CVA)
• Participants suffering from a substance use disorder, as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria. Recreational use of cannabis is allowed.
• Participants at high risk of suicide/suicidal ideation in the past one year assessed with the C-SSRS at screening
• Having another active implanted device such as a cardiac pacemaker, a spinal cord, peripheral nerve, sphenopalatine ganglion, or deep brain hypothalamic stimulator, and/or a drug delivery pump, etc.
• Cranial botulinum toxin injections in the past 3 months before enrolment. Administration of the following treatments in the last month before enrolment: monoclonal antibodies blocking calcitonin gene-related peptide transmission, suboccipital infiltrations with steroids and/or local anesthetics, oral steroids, radiofrequency procedure or infiltrations of the sphenopalatine ganglion, opioids WHO 3. Oral or systemic steroids are not allowed during the month before enrolment, except low doses (prednisone not superior to 10mg/day for no more than 7 days) if needed for other disorders.
• Medication overuse headache (ICHD 3 8.2)
• Inability to fill out an electronic diary.
• Previous surgery or trauma involving the cervical spine or the occipital bone
• Coagulopathy or required anticoagulant medications that cannot be safely discontinued in the perioperative period.
• Concurrent participation in another clinical study
• Planned pregnancy, pregnancy, or breastfeeding.