Migraine
Conditions
Brief summary
The main objective of this study is to have Phase III evidences of the efficacy of the Cefaly® Abortive Program device used at home for 2 hours to treat a migraine attack. This randomized, double-blind, sham-controlled trial will study the abortive treatment of migraine using the Cefaly® Abortive Program device.
Detailed description
The main objective of this study is to have Phase III evidences of the efficacy of the Cefaly® Abortive Program device used at home for 2 hours to treat a migraine attack, as triptans are generally used. That is to say having randomized, double-blind, sham-controlled data of the efficacy and safety of the Cefaly® Abortive Program device in the abortive treatment of acute migraine as measured by 2-hour pain freedom, pain relief and migraine-associated symptoms freedom, plus evolution of these measurements for 24 hours after the beginning of the treatment session.
Interventions
DEVICEVerum Cefaly® Abortive Program device
The Cefaly® Abortive Program device is an external cranial neurostimulator designed for supraorbital neurostimulation, also known as external Trigeminal Nerve Stimulation (e-TNS). The Verum Cefaly® Abortive Program device will deliver verum external trigeminal nerve stimulation.
DEVICESham Cefaly® Abortive Program device
The Cefaly® Abortive Program device is an external cranial neurostimulator designed for supraorbital neurostimulation, also known as external Trigeminal Nerve Stimulation (e-TNS). The Sham Cefaly® Abortive Program device will deliver sham external trigeminal nerve stimulation.
Sponsors
Cefaly Technology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age from 18 to 65 on the day of signing the informed consent form 2. ≥ 1-year history of migraine with or without aura according to the diagnostic criteria listed in International Classification of Headache Disorders (ICHD)-3 beta (2013) section 1, migraine, with the exception of aura without headache, hemiplegic migraine and brainstem aura migraine 3. Migraine onset before the age of 50 4. Having between 2 and 8 moderate or severe migraine attacks (Grade 2 or 3) per month in each of the two months prior to screening 5. Patient understands the study procedures, alternative treatments available, and voluntarily agrees to participate in the study by giving written informed consent 6. Patient is able to read and understand the written information (instruction sheet, paper diary and Adverse Events reporting form)
Exclusion criteria
1. Patient has difficulty distinguishing his/her migraine attacks from tension-type headaches 2. Patient has more than 15 headache days per month 3. Patient having received supraorbital nerve blocks in the prior 4 months 4. Patient having received Botox treatment in the prior 4 months 5. Modification of a migraine prophylaxis treatment in the previous 3 months 6. Diagnosis of other primary headache disorders, except rare (\< 4) tension-type headaches per month 7. Diagnosis of secondary headache disorders including Medication Overuse Headache (MOH) 8. Patient abusing opioids or user of recreational or illicit drugs or having had a recent history (within the last year) of drug or alcohol abuse or dependence 9. Implanted metallic or electronic device in the head 10. Cardiac pacemaker or implanted or wearable defibrillator 11. Patient having had a previous experience with the Cefaly® device 12. Migraine Aura without headache 13. Patient is currently participating or has participated in a study with an investigational compound or device in the last 30 days before the screening visit (Visit 1) 14. Patient not having the ability to use appropriately the device and/or to perform himself/herself or bear the first 20-minute stimulation session during the training test session at the study site
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Freedom at 2 Hours | 2 hours | The percentage of patients having a reduction of a moderate or severe migraine headache (Grade 2 or 3) at baseline to no headache (Grade 0) at 2 hours after the beginning of the e-TNS session. |
| Most Bothersome Migraine-associated Symptom Freedom at 2 Hours | 2 hours | The percentage of patients with absence, at 2 hours after the beginning of the e-TNS session, of the most bothersome migraine-associated symptom identified at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Use of Rescue Medication Between 2 and 24 Hours | 2-24 hours | The percentage of patients who took anti-migraine rescue medication between 2 and 24 hours after the beginning of the e-TNS session. |
| Pain Relief at 2 Hours | 2 hours | The percentage of patients having a reduction of a moderate or severe migraine headache (Grade 2 or 3) at baseline to a mild headache or to no headache (Grade 1 or 0) at 2 hours after the beginning of the e-TNS session. |
| Sustained Pain Relief at 24 Hours | 2-24 hours | The percentage of patients having mild or no headache (Grade 1 or 0) at 2 hours, with no use of anti-migraine rescue medication and no relapse of headache pain within the 24 hours after the beginning of the e-TNS session. |
| Sustained Pain Freedom at 24 Hours | 24 hours | The percentage of patients having no headache (Grade 0) at 2 hours, with no use of anti-migraine rescue medication and no relapse of headache pain within the 24 hours after the beginning of the e-TNS session. |
| Percentage of Patients With Absence of Photophobia, Phonophobia, Nausea, Vomiting at 2 Hours | 2 hours | The percentage of patients with absence of photophobia, phonophobia, nausea, vomiting at 2 hours after the beginning of the e-TNS session. |
Countries
United States
Participant flow
Recruitment details
Between April 10, 2018 and January 11, 2019, 626 subjects were screened for eligibility, and 607 were enrolled across ten centers in the United States.
Participants by arm
| Arm | Count |
|---|---|
| Verum 2-hour external trigeminal nerve stimulation with the Verum Cefaly® Abortive Program device, as abortive treatment of an early stage migraine attack
Verum Cefaly® Abortive Program device: The Cefaly® Abortive Program device is an external cranial neurostimulator designed for supraorbital neurostimulation, also known as external Trigeminal Nerve Stimulation (e-TNS). The Verum Cefaly® Abortive Program device will deliver verum external trigeminal nerve stimulation. | 259 |
| Sham 2-hour external trigeminal nerve stimulation with the Sham Cefaly® Abortive Program device, as abortive treatment of an early stage migraine attack
Sham Cefaly® Abortive Program device: The Cefaly® Abortive Program device is an external cranial neurostimulator designed for supraorbital neurostimulation, also known as external Trigeminal Nerve Stimulation (e-TNS). The Sham Cefaly® Abortive Program device will deliver sham external trigeminal nerve stimulation. | 279 |
| Total | 538 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 11 | 9 |
| Overall Study | Protocol Violation | 20 | 15 |
| Overall Study | Withdrawal by Subject | 9 | 5 |
Baseline characteristics
| Characteristic | Sham | Total | Verum |
|---|---|---|---|
| Age, Continuous | 42.0 years STANDARD_DEVIATION 12.3 | 41.14 years STANDARD_DEVIATION 12 | 40.22 years STANDARD_DEVIATION 11.62 |
| Headache pain severity Mild Pain | 0 Participants | 1 Participants | 1 Participants |
| Headache pain severity Moderate pain severity | 166 Participants | 321 Participants | 155 Participants |
| Headache pain severity No Pain | 0 Participants | 1 Participants | 1 Participants |
| Headache pain severity Severe pain severity | 113 Participants | 215 Participants | 102 Participants |
| Migraine Associated Symptom Nausea | 172 occurrences reported by subjects | 341 occurrences reported by subjects | 169 occurrences reported by subjects |
| Migraine Associated Symptom Phonophobia | 228 occurrences reported by subjects | 435 occurrences reported by subjects | 207 occurrences reported by subjects |
| Migraine Associated Symptom Photophobia | 259 occurrences reported by subjects | 506 occurrences reported by subjects | 247 occurrences reported by subjects |
| Migraine Associated Symptom Vomiting | 24 occurrences reported by subjects | 47 occurrences reported by subjects | 23 occurrences reported by subjects |
| Migraine type Migraine with aura | 111 Participants | 224 Participants | 113 Participants |
| Migraine type Migraine without aura | 168 Participants | 314 Participants | 146 Participants |
| Most Bothersome Symptom Nausea as MBS | 54 Participants | 109 Participants | 55 Participants |
| Most Bothersome Symptom Sensitivity to light as MBS | 183 Participants | 345 Participants | 162 Participants |
| Most Bothersome Symptom Sensitivity to sound as MBS | 35 Participants | 73 Participants | 38 Participants |
| Most Bothersome Symptom Vomiting as MBS | 7 Participants | 11 Participants | 4 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Sex: Female, Male Female | 229 Participants | 443 Participants | 214 Participants |
| Sex: Female, Male Male | 50 Participants | 95 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 298 | 0 / 303 |
| other Total, other adverse events | 22 / 259 | 8 / 279 |
| serious Total, serious adverse events | 0 / 298 | 1 / 303 |
Outcome results
Primary
Most Bothersome Migraine-associated Symptom Freedom at 2 Hours
The percentage of patients with absence, at 2 hours after the beginning of the e-TNS session, of the most bothersome migraine-associated symptom identified at baseline.
Time frame: 2 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Verum | Most Bothersome Migraine-associated Symptom Freedom at 2 Hours | 146 Participants |
| Sham | Most Bothersome Migraine-associated Symptom Freedom at 2 Hours | 118 Participants |
Primary
Pain Freedom at 2 Hours
The percentage of patients having a reduction of a moderate or severe migraine headache (Grade 2 or 3) at baseline to no headache (Grade 0) at 2 hours after the beginning of the e-TNS session.
Time frame: 2 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Verum | Pain Freedom at 2 Hours | 66 Participants |
| Sham | Pain Freedom at 2 Hours | 51 Participants |
Secondary
Pain Relief at 2 Hours
The percentage of patients having a reduction of a moderate or severe migraine headache (Grade 2 or 3) at baseline to a mild headache or to no headache (Grade 1 or 0) at 2 hours after the beginning of the e-TNS session.
Time frame: 2 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Verum | Pain Relief at 2 Hours | 180 Participants |
| Sham | Pain Relief at 2 Hours | 154 Participants |
Secondary
Percentage of Patients With Absence of Photophobia, Phonophobia, Nausea, Vomiting at 2 Hours
The percentage of patients with absence of photophobia, phonophobia, nausea, vomiting at 2 hours after the beginning of the e-TNS session.
Time frame: 2 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Verum | Percentage of Patients With Absence of Photophobia, Phonophobia, Nausea, Vomiting at 2 Hours | 110 Participants |
| Sham | Percentage of Patients With Absence of Photophobia, Phonophobia, Nausea, Vomiting at 2 Hours | 95 Participants |
Secondary
Sustained Pain Freedom at 24 Hours
The percentage of patients having no headache (Grade 0) at 2 hours, with no use of anti-migraine rescue medication and no relapse of headache pain within the 24 hours after the beginning of the e-TNS session.
Time frame: 24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Verum | Sustained Pain Freedom at 24 Hours | 59 Participants |
| Sham | Sustained Pain Freedom at 24 Hours | 44 Participants |
Secondary
Sustained Pain Relief at 24 Hours
The percentage of patients having mild or no headache (Grade 1 or 0) at 2 hours, with no use of anti-migraine rescue medication and no relapse of headache pain within the 24 hours after the beginning of the e-TNS session.
Time frame: 2-24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Verum | Sustained Pain Relief at 24 Hours | 119 Participants |
| Sham | Sustained Pain Relief at 24 Hours | 96 Participants |
Comparison: Identical statistical analyses were performed for the intent-to-treat (ITT) and the per protocol (PP) populations. The ITT population consisted of all randomized patients, who received any duration of sham or verum treatment and returned completed study materials. The PP population consisted of patients who strictly met inclusion criteria and completed at least 60 min of treatment.p-value: <0.05Chi-squared
Secondary
Use of Rescue Medication Between 2 and 24 Hours
The percentage of patients who took anti-migraine rescue medication between 2 and 24 hours after the beginning of the e-TNS session.
Time frame: 2-24 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Verum | Use of Rescue Medication Between 2 and 24 Hours | 82 Participants |
| Sham | Use of Rescue Medication Between 2 and 24 Hours | 105 Participants |