Occipital Nerve Stimulation in the Treatment of Migraine
Occipital Nerve Stimulation in the Treatment of Migraine
The objective of this proof-of-concept study is to generate initial safety and effectiveness
 data for the neuro-modulation stimulation (NMS) E-Box in patients with chronic migraine in an
 acute setting. The results of this study will determine if further development of this device
 in a larger study is warranted.
Inclusion Criteria:

 1. Adult ≥ 18 and ≤ 65 years of age females or males;

 2. Willing to participate in the study and to complete all study-related procedures,
 evaluations, and headache diaries;

 3. Able to understand, agree to, and sign the study's IRB-approved informed consent form;

 4. Has a physician-made diagnosis of Chronic Migraine as defined by the following (a, b,
 and c):

 1. Headache (tension-type and/or migraine) lasting a minimum of 4 hours on ≥15 days
 per month for at least 3 months and on ≥XX (redacted by sponsor to preserve
 integrity of study) days in the 30 days prior to the Screening Visit;

 2. Headaches on ≥8 days per month for at least 3 months that have fulfilled the
 following:

 i. Headaches with at least two of the following:

 -  unilateral location;

 -  pulsating quality;

 -  moderate or severe pain intensity;

 -  aggravation by or causing avoidance of routine physical activity (e.g. walking or
 climbing stairs);

 ii. AND at least one of the following:

 -  nausea and/or vomiting;

 -  photophobia and phonophobia;

 iii. OR headaches that have been treated and relieved by triptan(s) or ergot before
 the expected development of the symptoms listed in 4.b.i and 4.b.ii above;

 c. Headaches are not attributed to a substance or substance withdrawal, infection,
 cranial neuralgias, cluster headaches, autonomic cephalalgias, or cranial, cervical
 vascular, non-vascular, intracranial homeostasis and psychiatric disorders;

 5. If taking medication (prescribed or over-the-counter) for migraine prophylaxis, the
 medication must have been taken for at least 2 months and the dosage(s) must have been
 stable for at least 1 month prior to the Screening Visit. There must be no plan to add
 to, discontinue, or change the dose of these medications throughout the subject's
 participation in the study;

 6. To be eligible for the inpatient Treatment Period: the subject must have recorded in
 the Headache Diary ≥XX (redacted by sponsor to preserve integrity of study) headaches
 days (at least 4 hours of continuous head pain per headache day) in the 30 days
 immediately prior to the Inpatient Treatment Eligibility Visit (Visit 2);

 7. To be eligible for the inpatient Treatment Period: mean head pain severity of ≥XX
 (redacted by sponsor to preserve integrity of study) and ≤XX (redacted by sponsor to
 preserve integrity of study) based on the 11-point Numerical Rating Scale (NRS) in the
 30 days immediately prior to the Inpatient Treatment Eligibility Visit (Visit 2) [only
 data from headache days will be used to calculate the mean head pain severity; missing
 data on a headache day will be considered to be zero (0) for this calculation]; and

 8. To be eligible for the inpatient Treatment Period: The subject must be experiencing
 head pain on the day of the inpatient Treatment Eligibility Visit (Visit 2). Subjects
 may continue the Screening Period for another week if head pain is not present at
 Visit 2.

 Exclusion Criteria:

 1. Any head pain, including coexisting head pain, not attributable to Chronic Migraine as
 defined in this study's Inclusion Criterion #4;

 2. Any condition that could affect the subject's ability to assess the effect of
 neurostimulation or in which neurostimulation may be a safety concern, including but
 not limited to:

 1. Known history of epilepsy or recurrent seizures;

 2. Known neurogenic and neuromuscular disorders (i.e. myasthenia gravis, multiple
 sclerosis, autonomic disorders);

 3. Uncontrolled diabetes mellitus;

 4. Known peripheral neuropathy;

 3. History of taking the following medications in the 30 days prior to the Screening
 Visit:

 1. Opioid and opioid-containing medications;

 2. Butalbital, butalbital-containing, and barbiturate medications;

 3. Systemic corticosteroids (exceptions: acute corticosteroid medication including
 inhaled therapy (pulmonary), ocular therapy, or non-spinal intra-articular
 therapy);

 4. Urine drug screen that is positive for any of the tested drugs (i.e., cannabis,
 opiates, barbiturates, amphetamines , benzodiazepines and cocaine) at the Screening
 Visit (Visit 1) and the Inpatient Treatment Eligibility Visit (Visit 2);

 5. Positive pregnancy test at the Screening Visit (Visit 1) or at the Inpatient Treatment
 Eligibility Visit (Visit 2);

 6. Known history of cardiac conduction or heart rate abnormalities associated with
 symptoms;

 7. Uncontrolled hypertension;

 8. Any tattoos or extensive tissue scarring in the cervical/occipital area;

 9. Any active skin lesions, skin damage, broken skin, history of easy bruising or
 bleeding disorders, or history of surgery and/or trauma in the cervical/occipital area
 at the time of the Screening Visit;

 10. History of occipital nerve (ON) block, peripheral ON stimulation, or botulinum toxin
 (e.g., Botox) for treatment of headaches within the 90 days prior to the Screening
 Visit;

 11. Radiofrequency rhizolysis involving the occipital nerve or cervical nerves;

 12. Surgery involving the occipital nerve or cervical nerves (e.g. neurectomy or
 rhizotomy), or cervical ganglionectomy;

 13. History of craniotomy or intracranial surgery;

 14. Presence of metallic implant (e.g., metal pin, staple, clip) in the skull or neck
 area;

 15. Presence of any implanted neuromodulation or cardiac device;

 16. Severe or uncontrolled psychiatric disorders (i.e. schizophrenia, depression, anxiety,
 or at investigator discretion);

 17. Any other medical condition, concomitant medication or finding for which, at the
 discretion of the investigator, the subject should be excluded for reasons of safety
 or capacity for study compliance; or

 18. Participation in any other clinical study (not to include registries or survey-only
 studies) within 30 days or 5 half lives of an investigational drug, whichever is
 longer, of Visit 1 (Screening Visit) and for the duration of the study.