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

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.

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.

Study Overview

• Status: Completed
• Conditions: Cluster Headache
• Intervention / Treatment: Device: gammaCore

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, DK-2600
    • Glostrup Hospital, Danish Headache Centre
• Germany
  • Essen, Germany, D-45147
    • Westdeutches Kopfschmerzzentrum
  • Königstein im Taunus, Germany, D-61462
    • Kopfschmerzklinik Königstein
  • Munich, Germany, D-81377
    • Klinikum Grosshadern, University of Munich
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center, Neurology Department, K5-Q-104
• United Kingdom
  • East Yorkshire
    • Hull, East Yorkshire, United Kingdom, HU3 2JZ
      • Hull Royal Infirmary, Neurology Department
  • Greater London
    • London, Greater London, United Kingdom, NW3 2QG
      • Royal Free, Dept for Neurology and Clinical Neurosciences
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G51 4TF
      • The Southern Hospital, Neurology Department
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L9 7LJ
      • The Walton Center, Neurology Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: ElectroCore INC
• Investigators: Principal Investigator: Peter J. Goadsbury, Prof., Royal Free Hospital, Dept for Neurology and Clinical Neurosciences

Publications and helpful links

General Publications

• 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.

Helpful Links

• Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A randomized, double-blind, sham-controlled ACT2 study.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: October 4, 2013
• First Submitted That Met QC Criteria: October 7, 2013
• First Posted (Estimate): October 8, 2013

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: vagus nerve stimulation; cluster headache; VNS; vagal nerve stimulation; nVNS; non invasive; gammacore
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Trigeminal Autonomic Cephalalgias; Headache; Cluster Headache
• Other Study ID Numbers: GC-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The study is publlished and no other IPD data will be shared.