Chronic Cluster HeadachePhase 2NCT01701245
Prevention and Acute Treatment of Chronic Cluster Headache Compared to Standard of Care
A Phase 2 study testing GammaCore in people with Chronic Cluster Headache, run by ElectroCore INC at 10 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Cluster Headache
- What is being tested?
- GammaCore
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 97 participants
- Where
- 10 sitesin 4 countries
- Study dates
- Oct 2012to Oct 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
- 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
Show all 12Show fewer
- 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.
Who cannot join
- 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).
Show all 18Show fewer
- 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.
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
Germany5 sites
Neurologische Klinik und Poliklinik
Berlin, State of Berlin, D-10117
Krankenhaus Lindenbrunn, Department of Neurology
Coppenbrügge, Coppenbrügge, D-31863
Westdeutsches Kopfschmerzzentrum
Hufelandstr. 26, Hesse, D-45147
Migräne- und Kopfschmerzklinik Königstein
Königstein im Taunus, Königstein Im Taunus, D-61462
Department of Neurology, University of Munich
Munich, Munich, D-813 77
United Kingdom3 sites
The Southern Hospital, Neurology Department
Glasgow, Scotland, G51 4TF
Hull Royal Infirmary, Neurology Department
Hull, HU3 2JZ
The Walton Centre, Neurology Department
Liverpool, L9 7LJ
Italy1 site
Regional Referral Headache Centre Sant' Andrea Hospital
Rome, Rome, IT-00189
About this study
Official title: A Randomized, Multicenter Study for the Prevention and Acute Treatment of Chronic Cluster Headache Using Gammacore, Versus Standard of Care.
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.
Read the 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.
- Conditions
- Chronic Cluster Headache
- Being tested
- GammaCore
- Keywords
- vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, cluster headache, chronic, non invasive, gammacore
- Medical subject headings
- Cluster Headache, Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GammaCoreDevice
vagal stimulation
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | No intervention | No intervention, standard of care |
| GammaCore | Active comparator | 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. Receives: Device: GammaCore |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks
Secondary outcomes (3)
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
Measured: baseline (2 weeks) and random period(last 2 weeks)
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.
Measured: 10 weeks
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
Measured: 10 weeks (baseline 2 weeks, random 4 weeks and open label 4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2012 (estimated)
- Study startOct 2012
- Primary completionMar 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Cluster HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 97 participants (actual)
Sponsor and investigators
- Lead sponsor
- ElectroCore INC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Charly Gaul, Dr med, Principal investigator, Migräne- und Kopfschmerzklinik Königstein
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01701245
- Sponsor's protocol ID
- GC-002
- Status last verified
- Mar 2016
- First submitted
- 3 Oct 2012
- Last updated
- 25 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Not planned to share individual data
Publications
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.
PubMed 27102120
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multicenter Study for the Prevention and Acute Treatment of Chronic Cluster Headache Using Gammacore, Versus Standard of Care.
- ClinicalTrials.gov ID
- NCT01701245
- Acronym / sponsor ID
- GC-002
- Conditions
- Chronic Cluster Headache
- Keywords
- vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, cluster headache, chronic, non invasive, gammacore
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 97 participants (actual)
- Lead sponsor
- ElectroCore INCIndustry (pharma, biotech, devices)
- Study start
- Oct 2012
- Primary completion
- Mar 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 5 Oct 2012 (estimated)
- Results
- Posted 25 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of care | No intervention | –No intervention, standard of care |
| GammaCore | Active comparator | Device: GammaCoreThree 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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):
- 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
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GammaCorevagal stimulation | Device | GammaCore |
Primary outcome
A Change in the Frequency of Cluster Headache Attacks Per Week
Time frame: 4 weeks
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.
3 secondary outcomes
Pain Relief of Headache Attacks
Time frame: baseline (2 weeks) and random period(last 2 weeks)
Adverse Events
Time frame: 10 weeks
EQ-5D-3L (EuroQoL 5 Questions and 3 Answering Levels) and a VAS (Visual Analogue Scale)
Time frame: 10 weeks (baseline 2 weeks, random 4 weeks and open label 4 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27102120Morris 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.
- Individual participant dataSharing planned: No. Not planned to share individual data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charly Gaul, Dr med principal investigator
Migräne- und Kopfschmerzklinik Königstein
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GammaCore in people with Chronic Cluster Headache, run by ElectroCore INC at 10 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, United Kingdom, Belgium, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A Change in the Frequency of Cluster Headache Attacks Per Week (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01701245, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2016.