Clinical trial NCT01855672: Occipital Nerve Stimulation in the Treatment of Migraine
Official title: A Multicenter, Randomized, Controlled, Double-Blind, Proof-of-Concept Study Assessing the Safety and Effectiveness of a Signal Generator Device (NMS EBox) for the Treatment of Chronic Migraine
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Migraine
Keywords: Migraine, occipital nerve, stimulation
Lead sponsor: Ethicon, Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-16
Enrollment: 1
Sex: ALL
Minimum age (years): 8
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Reduction of Head Pain Severity
timeFrame: Over 96-hours treatment period
Secondary outcomes:
measure: Rates of Reduction in Severity of Head Pain
timeFrame: Over the 96-hour treatment period
measure: Time with No Head Pain
timeFrame: Over the 96-hour Treatment Period
measure: Presence of Symptoms
timeFrame: Over the 96-hour treatment period
measure: Severity of Symptoms
timeFrame: Over the 96-hour treatment period
measure: Use of Medication
timeFrame: Over the 96-hour treatment period
measure: Impairment
timeFrame: Over the 96-hour treatment period
measure: Sleep Quality
timeFrame: Over the 96-hour treatment period
measure: PGIC
timeFrame: End of the 96-hour treatment period
measure: CGIC
timeFrame: End of the 96-hour treatment period
measure: PGIC Migraine
timeFrame: End of the 96-hour treatment period
measure: PGIC Sleep
timeFrame: End of the 96-hour treatment period
Other outcomes:
measure: Safety
timeFrame: Over the treatment and follow-up periods
Locations:
city: Newington
country: United States
facility: ActivMed
state: New Hampshire
city: New York
country: United States
facility: Clinilabs
state: New York
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
city: Philadelphia
country: United States
facility: TJU
state: Pennsylvania
Study officials:
affiliation: Janssen, LP
name: David Biondi, DO
role: STUDY_DIRECTOR
affiliation: Ethicon, Inc.
name: Jeff Hammond, MD
role: STUDY_DIRECTOR
References: