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Prevention and Acute Treatment of Chronic Cluster Headache Compared to Standard of Care

Primary Purpose

Chronic Cluster Headache

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GammaCore
Sponsored by
ElectroCore INC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Cluster Headache focused on measuring vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, cluster headache, chronic, non invasive, gammacore

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

1. Signed Informed Consent Form 2. Subjects between the age of 18-70, both genders 3. Subjects diagnosed with chronic cluster headache for at least 1 year, without remission periods or with remission periods lasting <1 month, in accordance with the ICHD-II classification criteria (2ndEd):

a. At least 5 attacks fulfilling the following criteria: i. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated ii. Headache is accompanied by at least 1 of the following:

  1. Ipsilateral conjunctival injection and/or lacrimation
  2. Ipsilateral nasal congestion and/or rhinorrhea
  3. Ipsilateral eyelid oedema
  4. Ipsilateral forehead and facial sweating
  5. Ipsilateral miosis and/or ptosis
  6. A sense of restlessness or agitation iii. Attacks have a frequency from 1 every other day to 8 per day and are not attributed to another disorder iv. Attacks recur over > 1 year without remission periods or with remission periods lasting < 1 month.

4. Has minimum mean attack frequency of 4 CH attacks per week. 5. Is able to distinguish CH from other headaches (i.e. tension-type headaches).

6. Is capable of completing headache pain self-assessments. 7. Agrees to use the GammaCore® device as intended and follow all of the requirements of the study, including follow-up visit requirements.

8. Is willing to keep all concomitant medication stable during the entire study period.

9. Women of child-bearing potential must use 2 methods of contraceptive i.e. hormones and condom.

Exclusion Criteria:

  1. Is currently taking CH prophylactic medication for indications other than CH which in the opinion of the clinician may interfere with the study
  2. Has had a change in type or dosage of prophylactic headache medications < 1 month prior to enrollment
  3. Has a history of intracranial or carotid aneurysm, intracranial hemorrhage, brain tumors or significant head trauma.
  4. Has a lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the GammaCore® treatment site.
  5. Has other significant pain problem that might confound the study assessments in the opinion of the investigator.
  6. Has 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 (within 5years).
  7. Has had a previous unilateral or bilateral vagotomy.
  8. Has uncontrolled high blood pressure.
  9. 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.
  10. Has a history of carotid endarterectomy or vascular neck surgery on the right side.
  11. Has been implanted with metal cervical spine hardware or has a metallic implant near the GammaCore® stimulation site.
  12. Has a history, the last 12 month, of syncope.
  13. Has a history, the last 12 month of seizures.
  14. Has a known history or suspicion of substance abuse or addiction, or overuse of acute headache medication for headaches other than CH.
  15. Has psychiatric or cognitive disorder and/or behavioral problems which in the opinion of the investigator may interfere with the study
  16. In the opinion of the investigator the subject is incapable of operating the GammaCore® device as intended and performing the data collection procedures.
  17. Is participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days.
  18. Woman who are pregnant or lactating.

Sites / Locations

  • University Department of Neurology CHR
  • Westdeutsches Kopfschmerzzentrum
  • Neurologische Klinik und Poliklinik
  • Krankenhaus Lindenbrunn, Department of Neurology
  • Migräne- und Kopfschmerzklinik Königstein
  • Department of Neurology, University of Munich
  • Regional Referral Headache Centre Sant' Andrea Hospital
  • The Southern Hospital, Neurology Department
  • Hull Royal Infirmary, Neurology Department
  • The Walton Centre, Neurology Department

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

Standard of care

GammaCore

Arm Description

No intervention, standard of care

Three stimulation treatments 2x/day 7 to 10 hours apart from one another. In addition, three stimulation treatments at the time of onset of symptoms of a headache attack.

Outcomes

Primary Outcome Measures

A Change in the Frequency of Cluster Headache Attacks Per Week
The primary endpoint is the reduction in mean number of CH attacks per week. The number of CH attacks will be calculated as the sum of all attacks over the days in the run-in period and divided by the number of weeks, respectively for the last 14 days of treatment during the randomised phase. The reduction will then be the number of CH attacks during treatment period (last 14 days of the randomized treatment period) - number of CH attacks during run-in.

Secondary Outcome Measures

Pain Relief of Headache Attacks
The median pain during baseline (2 weeks) will be compared with the last 14 days of the treatment period Scale 0-4 0= no pain mild pain moderate pain severe pain very severe pain
Adverse Events
The frequency of device effects will be compared between the two treatment groups. Only effects which are new after baseline or have increased severity after baseline will be used in the comparison.
EQ-5D-3L (EuroQoL 5 Questions and 3 Answering Levels) and a VAS (Visual Analogue Scale)
The EQ-5D-3L (EuroQoL 5 questions and 3 answering levels) during the run-in period will be compared with the EQ-5D-3L during the treatment period. And treatment period will be compared to open label. Rating of questions Level 1 no problems Level 2 some problems Level 3 Significant problems Worst case is 15 points and best case is 5 points using index Visual analogue scale VAS 0-100 where 0 is the worst imaginable health state and 100 the best imaginable health state

Full Information

First Posted
October 3, 2012
Last Updated
March 23, 2016
Sponsor
ElectroCore INC
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1. Study Identification

Unique Protocol Identification Number
NCT01701245
Brief Title
Prevention and Acute Treatment of Chronic Cluster Headache Compared to Standard of Care
Official Title
A Randomized, Multicenter Study for the Prevention and Acute Treatment of Chronic Cluster Headache Using Gammacore, Versus Standard of Care.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
October 2014 (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
Subjects enrolled into this 10 week study will for the first two weeks document the number of cluster headaches and the means of treating (medication) of these attacks. Subjects will then be randomized to into either two groups. The first group is continuing with standard of care and the second group is treatment with the investigational device (GammaCore) for a period of 4 weeks. After this 4 week period, all subjects will treat with the GammaCore for another 4 week period. It is hypothesized the the treatment group will have a reduction in mean cluster headaches per week by 50% compared to the standard of care group.
Detailed Description
The study is a prospective randomized controlled multi-center investigation designed for comparison of two parallel groups, GammaCore® (active treatment) and Standard of Care, SoC, (control). The study period begins with a 2 week run-in period, followed by a 4 week comparative period when the subjects are randomized to either active treatment or control 1:1. The comparative period will be followed by a period where all subject will receive GammaCore® for 4 weeks.After the subject signed the Consent Form for participation the baseline (visit1) data will be collected. Subject will be informed how to complete the 2 week diary during the run-in period During the run-in period, all subjects will use stable SoC according to their individual prescriptions. The subject will record as CH attack regarding duration and frequency and the use of medication and oxygen. Once subjects have finalized the run-in period, they are randomized to continue in 4 weeks comparative period. During this period, the control group continues with stable SoC and the active group is provided with a GammaCore® device for prophylactic and acute treatment in addition to the stable SoC Subjects stimulate 3 x 2 times daily as part of the prophylactic treatment regimen (cervical vagal nerve). Three 90 second stimulations are self-administered by the subject with 5 minutes between each stimulation on the right side of the neck. This preventive stimulation regimen is performed: First Daily Treatment - within 1 hour of waking Second Daily Treatment - 7-10 hours following the first daily treatment Acute CH attack: 3 x 90 second treatments consecutively at the onset of pain or symptoms. If the attack is not aborted within 15 minutes the subject should be informed to take SOC abortive medication. If an acute cluster headache attack is treated with the GammaCore® device, the subject will try to work within the preventive treatment window to avoid a preventive treatment in the 2-hour refractory period following the acute treatment. A total of minimally 6 stimulations for the preventive part and as needed for the acute attacks. The active group also continues with the stable SoC during the entire 4 weeks period. Both groups record all CH attacks in the diary together with medication and oxygen use. All adverse events shall also be recorded in the diary. The end of the 4 week comparative period marks the completion of the randomized part of the study, however all subjects are provided the option to continue to a 4 week GammaCore® treatment with the same stimulation parameter as during the 4 week randomization period. All subjects randomized to the SoC group will receive training. During the entire study period, subjects are allowed to take rescue medication including oxygen inhalation for abortion of CH attacks. The amount and doses of the medication and oxygen are recorded in the diary.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Cluster Headache
Keywords
vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, cluster headache, chronic, non invasive, gammacore

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
97 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard of care
Arm Type
No Intervention
Arm Description
No intervention, standard of care
Arm Title
GammaCore
Arm Type
Active Comparator
Arm Description
Three stimulation treatments 2x/day 7 to 10 hours apart from one another. In addition, three stimulation treatments at the time of onset of symptoms of a headache attack.
Intervention Type
Device
Intervention Name(s)
GammaCore
Intervention Description
vagal stimulation
Primary Outcome Measure Information:
Title
A Change in the Frequency of Cluster Headache Attacks Per Week
Description
The primary endpoint is the reduction in mean number of CH attacks per week. The number of CH attacks will be calculated as the sum of all attacks over the days in the run-in period and divided by the number of weeks, respectively for the last 14 days of treatment during the randomised phase. The reduction will then be the number of CH attacks during treatment period (last 14 days of the randomized treatment period) - number of CH attacks during run-in.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Pain Relief of Headache Attacks
Description
The median pain during baseline (2 weeks) will be compared with the last 14 days of the treatment period Scale 0-4 0= no pain mild pain moderate pain severe pain very severe pain
Time Frame
baseline (2 weeks) and random period(last 2 weeks)
Title
Adverse Events
Description
The frequency of device effects will be compared between the two treatment groups. Only effects which are new after baseline or have increased severity after baseline will be used in the comparison.
Time Frame
10 weeks
Title
EQ-5D-3L (EuroQoL 5 Questions and 3 Answering Levels) and a VAS (Visual Analogue Scale)
Description
The EQ-5D-3L (EuroQoL 5 questions and 3 answering levels) during the run-in period will be compared with the EQ-5D-3L during the treatment period. And treatment period will be compared to open label. Rating of questions Level 1 no problems Level 2 some problems Level 3 Significant problems Worst case is 15 points and best case is 5 points using index Visual analogue scale VAS 0-100 where 0 is the worst imaginable health state and 100 the best imaginable health state
Time Frame
10 weeks (baseline 2 weeks, random 4 weeks and open label 4 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. Signed Informed Consent Form 2. Subjects between the age of 18-70, both genders 3. Subjects diagnosed with chronic cluster headache for at least 1 year, without remission periods or with remission periods lasting <1 month, in accordance with the ICHD-II classification criteria (2ndEd): a. At least 5 attacks fulfilling the following criteria: i. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes if untreated ii. Headache is accompanied by at least 1 of the following: Ipsilateral conjunctival injection and/or lacrimation Ipsilateral nasal congestion and/or rhinorrhea Ipsilateral eyelid oedema Ipsilateral forehead and facial sweating Ipsilateral miosis and/or ptosis A sense of restlessness or agitation iii. Attacks have a frequency from 1 every other day to 8 per day and are not attributed to another disorder iv. Attacks recur over > 1 year without remission periods or with remission periods lasting < 1 month. 4. Has minimum mean attack frequency of 4 CH attacks per week. 5. Is able to distinguish CH from other headaches (i.e. tension-type headaches). 6. Is capable of completing headache pain self-assessments. 7. Agrees to use the GammaCore® device as intended and follow all of the requirements of the study, including follow-up visit requirements. 8. Is willing to keep all concomitant medication stable during the entire study period. 9. Women of child-bearing potential must use 2 methods of contraceptive i.e. hormones and condom. Exclusion Criteria: Is currently taking CH prophylactic medication for indications other than CH which in the opinion of the clinician may interfere with the study Has had a change in type or dosage of prophylactic headache medications < 1 month prior to enrollment Has a history of intracranial or carotid aneurysm, intracranial hemorrhage, brain tumors or significant head trauma. Has a lesion (including lymphadenopathy), dysaesthesia, previous surgery or abnormal anatomy at the GammaCore® treatment site. Has other significant pain problem that might confound the study assessments in the opinion of the investigator. Has 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 (within 5years). Has had a previous unilateral or bilateral vagotomy. Has uncontrolled high blood pressure. 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. Has a history of carotid endarterectomy or vascular neck surgery on the right side. Has been implanted with metal cervical spine hardware or has a metallic implant near the GammaCore® stimulation site. Has a history, the last 12 month, of syncope. Has a history, the last 12 month of seizures. Has a known history or suspicion of substance abuse or addiction, or overuse of acute headache medication for headaches other than CH. Has psychiatric or cognitive disorder and/or behavioral problems which in the opinion of the investigator may interfere with the study In the opinion of the investigator the subject is incapable of operating the GammaCore® device as intended and performing the data collection procedures. Is participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days. Woman who are pregnant or lactating.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charly Gaul, Dr med
Organizational Affiliation
Migräne- und Kopfschmerzklinik Königstein
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Department of Neurology CHR
City
Liège
ZIP/Postal Code
B-4000
Country
Belgium
Facility Name
Westdeutsches Kopfschmerzzentrum
City
Hufelandstr. 26
State/Province
Essen
ZIP/Postal Code
D-45147
Country
Germany
Facility Name
Neurologische Klinik und Poliklinik
City
Berlin
ZIP/Postal Code
D-10117
Country
Germany
Facility Name
Krankenhaus Lindenbrunn, Department of Neurology
City
Coppenbrügge
ZIP/Postal Code
D-31863
Country
Germany
Facility Name
Migräne- und Kopfschmerzklinik Königstein
City
Königstein im Taunus
ZIP/Postal Code
D-61462
Country
Germany
Facility Name
Department of Neurology, University of Munich
City
Munich
ZIP/Postal Code
D-813 77
Country
Germany
Facility Name
Regional Referral Headache Centre Sant' Andrea Hospital
City
Rome
ZIP/Postal Code
IT-00189
Country
Italy
Facility Name
The Southern Hospital, Neurology Department
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Facility Name
Hull Royal Infirmary, Neurology Department
City
Hull
ZIP/Postal Code
HU3 2JZ
Country
United Kingdom
Facility Name
The Walton Centre, Neurology Department
City
Liverpool
ZIP/Postal Code
L9 7LJ
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Not planned to share individual data
Citations:
PubMed Identifier
27102120
Citation
Morris J, Straube A, Diener HC, Ahmed F, Silver N, Walker S, Liebler E, Gaul C. Cost-effectiveness analysis of non-invasive vagus nerve stimulation for the treatment of chronic cluster headache. J Headache Pain. 2016;17:43. doi: 10.1186/s10194-016-0633-x. Epub 2016 Apr 22.
Results Reference
derived

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Prevention and Acute Treatment of Chronic Cluster Headache Compared to Standard of Care

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