Cluster Headache
Conditions
Keywords
vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, cluster headache, non invasive, gammacore
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.
Interventions
DEVICEgammaCore
Vagal stimulation
Sponsors
ElectroCore INC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of the Headache Pain Free Attack Rates at 15 Minutes Following the Treatment | 2 weeks | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Disability From Baseline (Randomization) to 2 Weeks After Baseline | 2 weeks | 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. 1. minor 2. minor/moderate 3. moderate 4. moderate/severe 5. severe |
| Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | 2 weeks | 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 | 2 weeks | 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 | 2 weeks | 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 |
Countries
Denmark, Germany, Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| gammaCore Active Comparator: gammacore gammacore active device to be used noninvasively to the vagal nerve in the neck | 50 |
| Sham Device Placebo Comparator: inactive gammacore same as the active treatment, but without the therapy treatment provided | 52 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Missing diary data | 2 | 6 |
| Overall Study | No headache attacks | 0 | 2 |
Baseline characteristics
| Characteristic | gammaCore | Sham Device | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 52 Participants | 101 Participants |
| Age, Continuous | 43.9 years STANDARD_DEVIATION 10.6 | 46.9 years STANDARD_DEVIATION 10.63 | 45.4 years STANDARD_DEVIATION 10.67 |
| Region of Enrollment Denmark | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Germany | 7 participants | 9 participants | 16 participants |
| Region of Enrollment Netherlands | 16 participants | 14 participants | 30 participants |
| Region of Enrollment United Kingdom | 25 participants | 27 participants | 52 participants |
| Sex: Female, Male Female | 15 Participants | 14 Participants | 29 Participants |
| Sex: Female, Male Male | 35 Participants | 38 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 52 |
| other Total, other adverse events | 20 / 50 | 14 / 52 |
| serious Total, serious adverse events | 1 / 50 | 1 / 52 |
Outcome results
Primary
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.
Time frame: 2 weeks
Population: ITT-Intention To Treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| gammaCore | Comparison of the Headache Pain Free Attack Rates at 15 Minutes Following the Treatment | Number of treated attacks | 495 Number of attacks |
| gammaCore | Comparison of the Headache Pain Free Attack Rates at 15 Minutes Following the Treatment | Number of treated attack pain free at 15 minutes | 67 Number of attacks |
| Sham Device | Comparison of the Headache Pain Free Attack Rates at 15 Minutes Following the Treatment | Number of treated attacks | 400 Number of attacks |
| Sham Device | Comparison of the Headache Pain Free Attack Rates at 15 Minutes Following the Treatment | Number of treated attack pain free at 15 minutes | 46 Number of attacks |
Secondary
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. 1. minor 2. minor/moderate 3. moderate 4. moderate/severe 5. severe
Time frame: 2 weeks
Population: Safety population, three patients in the Sham device group have no data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| gammaCore | Change in Disability From Baseline (Randomization) to 2 Weeks After Baseline | Disability score at baseline | 3.9 units on a scale | Standard Error 0.2 |
| gammaCore | Change in Disability From Baseline (Randomization) to 2 Weeks After Baseline | Disability score at 2 weeks | 3.3 units on a scale | Standard Error 0.2 |
| Sham Device | Change in Disability From Baseline (Randomization) to 2 Weeks After Baseline | Disability score at baseline | 3.7 units on a scale | Standard Error 0.2 |
| Sham Device | Change in Disability From Baseline (Randomization) to 2 Weeks After Baseline | Disability score at 2 weeks | 3.2 units on a scale | Standard Error 0.2 |
Secondary
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
Time frame: 2 weeks
Population: ITT-Intention To Treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| gammaCore | Comparison of the Headache Pain Free Attack Rates at 30 Minutes Following the Treatment | Number of attacks treated | 495 Number of attacks |
| gammaCore | Comparison of the Headache Pain Free Attack Rates at 30 Minutes Following the Treatment | Number of attacks treated and pain free at 30 min. | 101 Number of attacks |
| Sham Device | Comparison of the Headache Pain Free Attack Rates at 30 Minutes Following the Treatment | Number of attacks treated | 400 Number of attacks |
| Sham Device | Comparison of the Headache Pain Free Attack Rates at 30 Minutes Following the Treatment | Number of attacks treated and pain free at 30 min. | 81 Number of attacks |
Secondary
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).
Time frame: 2 weeks
Population: Safety population, three patients in the Sham group had no data for EQ-5D-3L
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Mobility after 2 weeks | 1.3 units on a scale | Standard Error 0.1 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Selfcare after 2 weeks | 1.1 units on a scale | Standard Error 0 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Pain after 2 weeks | 1.7 units on a scale | Standard Error 0.1 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Activity after 2 weeks | 1.6 units on a scale | Standard Error 0.1 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Anxiety at baseline | 1.5 units on a scale | Standard Error 0.1 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Selfcare at baseline | 1.1 units on a scale | Standard Error 0 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Anxiety after 2 weeks | 1.3 units on a scale | Standard Error 0.1 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Pain at baseline | 2.1 units on a scale | Standard Error 0.1 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | VAS scale at baseline | 58.9 units on a scale | Standard Error 2.5 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Mobility at baseline | 1.2 units on a scale | Standard Error 0.1 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | VAS scale after 2 weeks | 61.4 units on a scale | Standard Error 2.5 |
| gammaCore | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Activity baseline | 1.7 units on a scale | Standard Error 0.1 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | VAS scale after 2 weeks | 66.5 units on a scale | Standard Error 2.1 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Selfcare at baseline | 1.1 units on a scale | Standard Error 0 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Selfcare after 2 weeks | 1.1 units on a scale | Standard Error 0 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Activity baseline | 1.6 units on a scale | Standard Error 0.1 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Activity after 2 weeks | 1.6 units on a scale | Standard Error 0.1 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Mobility at baseline | 1.2 units on a scale | Standard Error 0.1 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Pain at baseline | 1.9 units on a scale | Standard Error 0.1 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Pain after 2 weeks | 1.8 units on a scale | Standard Error 0.1 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Anxiety at baseline | 1.6 units on a scale | Standard Error 0.1 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Anxiety after 2 weeks | 1.5 units on a scale | Standard Error 0.1 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | VAS scale at baseline | 63.7 units on a scale | Standard Error 2.1 |
| Sham Device | Mean Change of Questionnaire EQ-5D-3L (Euroqol- 5D-3L) From Baseline to After 2 Weeks Treatment | Mobility after 2 weeks | 1.1 units on a scale | Standard Error 0.1 |
Secondary
Patients Who Used Any Type of Rescue Medication
Following treatment at 15 minutes, patients recorded use of any rescue medication(s) in the diary'
Time frame: 2 weeks
Population: ITT-Intention To Treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| gammaCore | Patients Who Used Any Type of Rescue Medication | 40 participants |
| Sham Device | Patients Who Used Any Type of Rescue Medication | 42 participants |