A Randomized Multicentre Study for the Acute Relief of Episodic and Chronic Cluster Headache.

Study Overview
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Brief Summary
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The study will look at a non-invasive treatment for people suffering with chronic and episodic headaches. Study subjects will be randomized to an active treatment or an in-active treatment for 2 weeks. After the 2 weeks all subjects will continue to treat with an active treatment for an additional 2 weeks.

Detailed Description
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The study is a prospective double blind, randomized, sham-controlled, multi-center investigation designed for comparison of two parallel groups, GammaCore® (active treatment) and a sham, (in-active) treatment. The study period begins with a 1-week run-in period, followed by a 2 week comparative period when the subjects are randomized (1:1) to either active treatment or sham (in-active) treatment. The comparative period will be followed by an open label 2 week period, where the subjects in the sham treatment group will switch in treatment assignment and receive an active treatment and the active group will continue to receive an active treatment.

Official Title
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A Randomized, Multicentre, Double-blind, Parallel, Sham-controlled Study of GammaCore®, a Non-invasive Neurostimulator Device for the Acute Relief of Episodic and Chronic Cluster Headache.

Conditions
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Cluster Headache

Intervention / Treatment
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* Device: gammaCore


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is 18 years or older Has been diagnosed with episodic or chronic cluster headache in accordance with the ICHD-2 Classification criteria (2ndEd) Is capable of completing the 5-point pain scale, disability scale and other self-assessments Agrees to refrain from starting new medication aimed to control the cluster headache for the duration of the run-in and randomized phase Is able to provide written Informed Consent Exclusion Criteria:1. Episodic cluster headache sufferers who are not in a cluster headache bout at the time of screening and enrollment 2. Need to commence treatment with oral or injectable steroids for eventual concomitant medical conditions 3. Has a lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the GammaCore® treatment site 4. Is currently taking medication for indications other than CH that in the opinion of the clinician may interfere with the study 5. Has a history of any cranial aneurysm, intracranial haemorrhage, brain tumours or significant head trauma 6. Diagnosed or suspected secondary headache 7. Has other significant pain problem that might confound the study assessments in the opinion of the investigator 8. Has known or suspected severe atherosclerotic cardiovascular disease, severe carotid artery disease (e.g. bruits or history of transient ischemic attack (TIA) or cerebral vascular accident CVA), congestive heart failure (CHF), known severe coronary artery disease or recent (5 years) myocardial infarction 9. Has an 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) 10. Has had a previous, cervical vagotomy 11. Has uncontrolled high blood pressure 12. Is 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 13. Has a history of carotid endarterectomy or vascular neck surgery 14. Has been implanted with metal cervical spine hardware or has a metallic implant near the GammaCore stimulation site 15. Has a recent (12 months) or repeated history of syncope 16. Has a recent (12 months) or repeated history of seizure 17. Has a known history or suspicion of substance abuse or addiction, or overuse of acute headache medication 18. Has psychiatric or cognitive disorder and/or behavioural problems which in the opinion of the clinician may interfere with the study 19. Is pregnant, nursing, thinking of becoming pregnant in the next 6 weeks 20. Is participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days 21. Is a relative of or an employee of the investigator or the clinical study site

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: gammacore<br>gammacore active device to be used noninvasively to the vagal nerve in the neck. | Device: gammaCore<br>* Vagal stimulation<br>|
| Placebo Comparator: inactive gammacore<br>same as the active treatment, but without the therapy treatment provided | Device: gammaCore<br>* Vagal stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the Headache Pain Free Attack Rates at 15 Minutes Following the Treatment | Headache pain was collected at the beginning of the attack (all treated attacks) and 15 minutes post treatment pain free attacks. Data was collected in the patient diary. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Disability From Baseline (Randomization) to 2 Weeks After Baseline | Mean difference of scores on a 5 step disability scale. Disability was measured at baseline and after the randomization phase (2 weeks later). Lowest score is 1 and is better than the higher score at 5 that is the worst. An increase, higher scores, means worsening. minor minor/moderate moderate moderate/severe severe | 2 weeks | 
| Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | EQ-5D-3L descriptive system comprises 5 dimensions: mobility, self-care, activity, pain and anxiety. Each dimension has 3 levels: 1 = no problems, 2 = moderate problems, 3=extreme problems. Subjects indicate health state by ticking choosing appropriate statement in each dimension and a VAS scale (Overall health) from 0-100 mm where higher score is better (100) than lower score (0). Patients completed the EQ-5D-3L at baseline (the start of the randomized period and at 2 weeks). | 2 weeks | 
| Patients Who Used Any Type of Rescue Medication | Following treatment at 15 minutes, patients recorded use of any rescue medication(s) in the diary' | 2 weeks | 
| Comparison of the Headache Pain Free Attack Rates at 30 Minutes Following the Treatment | The headache pain was collected at the beginning of the attack and 30 minutes post treatment in the patient diary. The number of pain free (no pain) attacks are compared to all attacks treated | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nVNS, vagus nerve stimulation, vagal nerve stimulation, VNS, cluster headache, non invasive, gammacore