A Randomized Multicentre Study for the Acute Relief of Episodic and Chronic Cluster Headache.
Primary Purpose
Cluster Headache
Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
gammaCore
Sponsored by
About this trial
This is an interventional treatment trial for Cluster Headache focused on measuring vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, cluster headache, non invasive, gammacore
Eligibility Criteria
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
Sites / Locations
- Glostrup Hospital, Danish Headache Centre
- Westdeutches Kopfschmerzzentrum
- Kopfschmerzklinik Königstein
- Klinikum Grosshadern, University of Munich
- Leiden University Medical Center, Neurology Department, K5-Q-104
- Hull Royal Infirmary, Neurology Department
- Royal Free, Dept for Neurology and Clinical Neurosciences
- The Southern Hospital, Neurology Department
- The Walton Center, Neurology Department
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
gammacore
inactive gammacore
Arm Description
gammacore active device to be used noninvasively to the vagal nerve in the neck.
same as the active treatment, but without the therapy treatment provided
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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).
Patients Who Used Any Type of Rescue Medication
Following treatment at 15 minutes, patients recorded use of any rescue medication(s) in the diary'
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01958125
Brief Title
A Randomized Multicentre Study for the Acute Relief of Episodic and Chronic Cluster Headache.
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ElectroCore INC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cluster Headache
Keywords
vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, cluster headache, non invasive, gammacore
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
102 (Actual)
8. Arms, Groups, and Interventions
Arm Title
gammacore
Arm Type
Active Comparator
Arm Description
gammacore active device to be used noninvasively to the vagal nerve in the neck.
Arm Title
inactive gammacore
Arm Type
Placebo Comparator
Arm Description
same as the active treatment, but without the therapy treatment provided
Intervention Type
Device
Intervention Name(s)
gammaCore
Intervention Description
Vagal stimulation
Primary Outcome Measure Information:
Title
Comparison of the Headache Pain Free Attack Rates at 15 Minutes Following the Treatment
Description
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.
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Change in Disability From Baseline (Randomization) to 2 Weeks After Baseline
Description
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
Time Frame
2 weeks
Title
Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment
Description
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).
Time Frame
2 weeks
Title
Patients Who Used Any Type of Rescue Medication
Description
Following treatment at 15 minutes, patients recorded use of any rescue medication(s) in the diary'
Time Frame
2 weeks
Title
Comparison of the Headache Pain Free Attack Rates at 30 Minutes Following the Treatment
Description
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
Time Frame
2 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter J. Goadsbury, Prof.
Organizational Affiliation
Royal Free Hospital, Dept for Neurology and Clinical Neurosciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Glostrup Hospital, Danish Headache Centre
City
Glostrup
ZIP/Postal Code
DK-2600
Country
Denmark
Facility Name
Westdeutches Kopfschmerzzentrum
City
Essen
ZIP/Postal Code
D-45147
Country
Germany
Facility Name
Kopfschmerzklinik Königstein
City
Königstein im Taunus
ZIP/Postal Code
D-61462
Country
Germany
Facility Name
Klinikum Grosshadern, University of Munich
City
Munich
ZIP/Postal Code
D-81377
Country
Germany
Facility Name
Leiden University Medical Center, Neurology Department, K5-Q-104
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
Hull Royal Infirmary, Neurology Department
City
Hull
State/Province
East Yorkshire
ZIP/Postal Code
HU3 2JZ
Country
United Kingdom
Facility Name
Royal Free, Dept for Neurology and Clinical Neurosciences
City
London
State/Province
Greater London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
The Southern Hospital, Neurology Department
City
Glasgow
State/Province
Lanarkshire
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Facility Name
The Walton Center, Neurology Department
City
Liverpool
State/Province
Merseyside
ZIP/Postal Code
L9 7LJ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
The study is publlished and no other IPD data will be shared.
Citations:
PubMed Identifier
31246132
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.
Results Reference
derived
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/29231763
Description
Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A randomized, double-blind, sham-controlled ACT2 study.
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A Randomized Multicentre Study for the Acute Relief of Episodic and Chronic Cluster Headache.
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