Sphenopalatine Ganglion Stimulation for the Treatment of Chronic Cluster Headache

Inclusion Criteria:

• Age from ≥22 years old.

• Subject has been diagnosed with chronic cluster headache according to the 2013 ICHD, 3rd edition (beta version), criterion 3.1.2.

• Subject reports a minimum of 4 cluster attacks per week on the side of their dominantheadache laterality. Subjects who report more than 8 attacks per day or attackduration of less than 30 minutes (untreated or unsuccessfully treated) must have beentested to rule out other forms of trigeminal autonomic cephalalgias.

• Both subject and physician judge previously or currently used preventive and/or acutecluster headache treatment to be inadequate.

• Subject is able to distinguish cluster attacks from other headaches (i.e., migraine,tension-type headaches).

• Subject agrees to not use therapy involving TENS or magnetic field treatment while theNeurostimulator is implanted.

• Subject agrees to not participate in supplemental or alternative therapy, includingacupuncture and spinal manipulation, from Study Enrollment through the end of theExperimental Period of the study.

• Subject agrees to maintain current preventive headache medication regimens (no changein type, frequency, or dose) - except to manage tolerability - from Study Enrollmentthrough the Experimental Period of the study.

• Subject agrees not to use any acute medications, including oxygen therapy, for theirtreatable cluster attacks during the Experimental Period until after they have usedSPG stimulation therapy for at least 15 minutes.

• Subject has had a dental examination and cleaning in the past six (6) months.

• Subject has the ability to read and comprehend, and to reliably record information asrequired by the Protocol.

• Subject is able to provide written informed consent prior to participation in thestudy.

Exclusion Criteria:

• Subject's overall health, age and/or comorbidities place subject at high risk forcomplications from surgery and/or general anesthesia.

• Subject has had a change in type, dosage or dose frequency of preventive headachemedications < one (1) month prior to study enrollment

• Subject has been diagnosed with any other form of Trigeminal Autonomic Cephalalgias (e.g., paroxysmal hemicrania, SUNCT, etc.) or has a history of trigeminal neuralgia.

• Subject has undergone facial surgery in the area of the pterygopalatine fossa orzygomaticomaxillary buttress ipsilateral to the planned implant site that, in theopinion of the Investigator, may lead to an inability to properly implant theNeurostimulator.

• Subject currently has an active oral or dental abscess or an active maxillary sinusinfection based on present symptoms.

• Subject has been treated with therapeutic radiation to the facial region.

• Subject has been diagnosed with any major infectious processes such as osteomyelitis,or primary or secondary malignancies involving the face that have been active orrequired treatment in the past six (6) months.

• Subject has other significant pain problem(s) that, in the opinion of theInvestigator, might confound the study assessments.

• Subject is a woman of childbearing potential who is pregnant, nursing, or not usingcontraception.

• Subject is currently participating or has participated in the last month in anotherclinical study in which the subject has, is, or will be exposed to an investigationalor non-investigational drug or device.

• Subject has demonstrated or is believed to be at risk of non-compliance with studyprocedures (e.g., for completing the diary or maintaining a stable headache medicineregimen or returning for required follow-up visits).

• Subject is at risk of being unable to complete at least 1 year of follow-up (e.g., hasplans to relocate).

• Subject has had previous lesional radio-frequency (RF) ablation, balloon compression,gamma knife, or glycerol treatments of the ipsilateral sphenopalatine ganglion (SPG),trigeminal ganglion or any branch of the trigeminal nerve.

• Subject has had blocks or non-lesional pulsed RF of the ipsilateral SPG in the lastthree (3) months.

• Subject's pterygomaxillary fissure is less than 1.2 mm in width at the level of thevidian canal, as determined by CT scan.

• Subject has undergone onabotulinumtoxinA injections of the head and/or neck or has hadan occipital nerve block in the last three (3) months.

• Subject has or requires an active implanted medical device, such as apacemaker/defibrillator, other neurostimulator, or cochlear implant.

• Subject is expected to require diathermy, electroconvulsive therapy (ECT), ortranscranial magnetic stimulation (TMS).

• Subject has a history of bleeding disorders or coagulopathy and is unable todiscontinue anticoagulation, antiplatelet, or GP IIb IIIa inhibitor medication inpreparation for the implantation procedure.

• In the opinion of the Investigator, the subject currently meets criteria as defined bythe Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) for an activemajor depressive episode or for active significant psychiatric disorders, includingdementia, uncontrolled general anxiety disorder, psychotic disorders or uncontrolledbipolar disorder. Exclusion criteria also include: active psychosis, untreated severeanxiety disorder, homicidal ideation, significant Axis II disorders and significantuntreated sleep disorders.

• Subject currently has clinically significant drug or alcohol abuse as defined byDSM-IV-TR or is unable to refrain from substance abuse throughout the study.

• Subject has a history of malignancy or any other condition that requires MRImonitoring.

• Subject has a history of allergic or hypersensitive reactions to titanium, platinum,or implant grade silicone-polyurethane copolymers.

• Subject may be, in the opinion of the Investigator, at greater risk of infection (e.g., subjects with diabetes, taking steroids, with gingivitis/periodontitis,malnutrition or anorexia/bulimia) or at higher risk of harm from infections.

• Subject is currently using a tobacco cessation regimen (e.g. Wellbutrin, Zyban,Aplenzin, etc.).

• Subject is not suitable for the study for any reason (including overall health,pre-existing conditions or medications) in the judgment of the Investigator.