Clinical trial NCT01792817: Non-invasive Neurostimulation of the Vagus Nerve for the Treatment of Cluster Headache
Official title: Non-invasive Neurostimulation of the Vagus Nerve With the GammaCore Device for the Treatment of Cluster Headache
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cluster Headache
Keywords: Cluster Headache
GammaCore
vagal nerve stimulation
nVNS
VNS
non invasive
vagus nerve stimulation
Lead sponsor: ElectroCore INC
Sponsor class: INDUSTRY
First posted: 2013-02-15
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Multi-center, prospective, double-blind, randomized, sham-controlled pivotal study of non-invasive vagus nerve stimulation with the GammaCore® device for the acute treatment of cluster headache. The study compares the safety and effectiveness of an active treatment (GammaCore) against a sham treatment.

Detailed description: Phase 1: Prospective, randomized (1:1 active treatment:sham control allocation), double blinded, sham controlled treatment (active or sham) phase

Phase 2: Prospective, non-randomized, active treatment phase.

Phase 1 - Two Arms:

1. Active Treatment with the GammaCore Device
2. Sham Treatment with a placebo device

Phase 2 - One Arm:

Active Treatment with the GammaCore Device

Eligibility criteria: Inclusion Criteria:

1. Is between the ages of 18 and 75 years.
2. Has been diagnosed with cluster headache, in accordance with the ICHD-2

   Classification criteria (2ndEd):

   o At least 5 attacks fulfilling the following criteria:
   * Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated
   * Headache is accompanied by at least 1 of the following:
   * Ipsilateral conjunctival injection and/or lacrimation
   * Ipsilateral nasal congestion and/or rhinorrhea
   * Ipsilateral eyelid edema
   * Ipsilateral forehead and facial sweating
   * Ipsilateral miosis and/or ptosis
   * A sense of restlessness or agitation
3. currently experiencing cluster headaches, and from clinical history is expected to continue experiencing cluster headaches for a period of at least 4 weeks.
4. able to distinguish CH from other headaches (i.e. migraine, tension-type headaches).
5. capable of completing headache pain self-assessments.
6. \[Intentionally left blank\].
7. Agrees to use the GammaCore device as intended and follow all of the requirements of the study, including follow-up visit requirements.
8. Agrees to record usage of the GammaCore device, all required study data, and report any adverse device effects to the study center within 24 hours of any such adverse device effects.
9. able to provide written Informed Consent

Exclusion Criteria:

1. had surgery to treat cluster headache.
2. currently taking prophylactic medication (including chronic opioids and non-prescribed street drugs) for indications other than CH that in the opinion of the clinician may interfere with the study.
3. \[Intentionally left blank\].
4. undergone botulinum toxin injections in the head and/or neck in the last 3 months or nerve blocks (occipital or other) in the head or neck in the last month.
5. history of aneurysm, intracranial hemorrhage, brain tumors or significant head trauma.
6. lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the treatment site.
7. structural intracranial, or cervical vascular lesions that may potentially cause headache attacks.
8. other significant pain problem (including cancer pain, fibromyalgia, and trigeminal neuralgia/TAC-cluster) that might confound the study assessments.
9. known or suspected severe atherosclerotic cardiovascular disease, severe carotid artery disease (e.g. bruits or history of TIA or CVA), congestive heart failure (CHF), known severe coronary artery disease or recent myocardial infarction.
10. history of prolonged QT interval or a history of clinically significant arrhythmia.
11. abnormal baseline ECG (e.g. second and third degree heart block, atrial fibrillation, atrial flutter, recent history of ventricular tachycardia or ventricular fibrillation, or clinically significant premature ventricular contraction).
12. previous bilateral or right cervical vagotomy.
13. uncontrolled high blood pressure.
14. currently implanted with an electrical and/or neurostimulator device, including but not limited to cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant.
15. history of carotid endarterectomy or vascular neck surgery on the right side.
16. implanted with metal cervical spine hardware or has a metallic implant near the GammaCore stimulation site.
17. recent or repeated history of syncope.
18. recent or repeated history of seizure.
19. known history or suspicion of substance abuse or addiction, or overuse of acute headache medication for headaches other than CH.
20. psychiatric or cognitive disorder and/or behavioral problems which in the opinion of the clinician may interfere with the study.
21. pregnant, nursing, thinking of becoming pregnant in the next 4 months, or of childbearing years and is unwilling to use an accepted form of birth control.
22. participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days.
23. Belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with follow-up requirements, or provide self-assessments is compromised

Primary outcomes:
measure: Number of Participants With Repsonse to Treatment
timeFrame: 15 minutes post stimulation
Secondary outcomes:
measure: Sustained Treatment Success at 1 Hour Post-Treatment
timeFrame: For 1 hour post stimulation
measure: Average Mean Attack Intensities Experienced Per Subject
timeFrame: 15 minutes post-stimulation
measure: Incidence and Occurrence of Serious Adverse Events Related to Active or Sham Study Treatment and / or to Cluster Headache Events.
timeFrame: 4 weeks, Phase 1
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: California Medical Clinic for Headache
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Englewood
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: Fairfield
country: United States
facility: Associated Neurologists of Southern Connecticut
state: Connecticut
city: Tampa
country: United States
facility: Tampa General Hospital Headache Center
state: Florida
city: Chicago
country: United States
facility: Diamond Headache Clinic
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital and Clinics
state: Iowa
city: Louisville
country: United States
facility: Norton Neurology
state: Kentucky
city: Pikesville
country: United States
facility: Mid-Atlantic Headache Institute
state: Maryland
city: Worcester
country: United States
facility: New England Regional Headache Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Head Pain & Neurological Institute
state: Michigan
city: Springfield
country: United States
facility: Headache Care Center
state: Missouri
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: New York
country: United States
facility: Montefiore Headache Center
state: New York
city: Plainview
country: United States
facility: Center for Headache Care and Research at Island Neurological Associates, PC
state: New York
city: Chapel Hill
country: United States
facility: Carolina Headache Institute
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Jefferson Headache Center
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Morgantown
country: United States
facility: West Virginia University Dept of Neurology
state: West Virginia
Study officials:
affiliation: ElectroCore INC
name: Lia Spitzer
role: STUDY_DIRECTOR
References:
citation: de Coo IF, Marin JC, Silberstein SD, Friedman DI, Gaul C, McClure CK, Tyagi A, Liebler E, Tepper SJ, Ferrari MD, Goadsby PJ. Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A meta-analysis. Cephalalgia. 2019 Jul;39(8):967-977. doi: 10.1177/0333102419856607. Epub 2019 Jun 10.
citation: Silberstein SD, Mechtler LL, Kudrow DB, Calhoun AH, McClure C, Saper JR, Liebler EJ, Rubenstein Engel E, Tepper SJ; ACT1 Study Group. Non-Invasive Vagus Nerve Stimulation for the ACute Treatment of Cluster Headache: Findings From the Randomized, Double-Blind, Sham-Controlled ACT1 Study. Headache. 2016 Sep;56(8):1317-32. doi: 10.1111/head.12896.