A Phase III Trial of e-TNS for the Acute Treatment of Mig... | NCT03465904

NCT03465904

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Verum	Experimental	2-hour external trigeminal nerve stimulation with the Verum Cefaly® Abortive Program device, as abortive treatment of an early stage migraine attack	Device: Verum Cefaly® Abortive Program device
Sham	Sham Comparator	2-hour external trigeminal nerve stimulation with the Sham Cefaly® Abortive Program device, as abortive treatment of an early stage migraine attack	Device: Sham Cefaly® Abortive Program device

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Verum Cefaly® Abortive Program device	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	2 hours
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.	2 hours

Secondary Outcomes

Measure	Description	Time Frame
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.	2 hours
Percentage of Patients With Absence of Photophobia, Phonophobia, Nausea, Vomiting at 2 Hours

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age from 18 to 65 on the day of signing the informed consent form
≥ 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
Migraine onset before the age of 50
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
Patient understands the study procedures, alternative treatments available, and voluntarily agrees to participate in the study by giving written informed consent
Patient is able to read and understand the written information (instruction sheet, paper diary and Adverse Events reporting form)

Exclusion Criteria:

Patient has difficulty distinguishing his/her migraine attacks from tension-type headaches
Patient has more than 15 headache days per month
Patient having received supraorbital nerve blocks in the prior 4 months
Patient having received Botox treatment in the prior 4 months
Modification of a migraine prophylaxis treatment in the previous 3 months
Diagnosis of other primary headache disorders, except rare (< 4) tension-type headaches per month
Diagnosis of secondary headache disorders including Medication Overuse Headache (MOH)
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
Implanted metallic or electronic device in the head
Cardiac pacemaker or implanted or wearable defibrillator
Patient having had a previous experience with the Cefaly® device
Migraine Aura without headache
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)
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

Contacts/Locations Module

Name	Affiliation	Role
Deena Kuruvilla, M.D.	Yale University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Clinical Research Consortium		Tempe	Arizona	85283	United States
Pharmacology Research Institute

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
42231198	Derived	Johnson MAL, Panza G, Kuruvilla DE. Migraine phases and treatment response: a post hoc analysis of participants with migraine with aura from the TEAM study. BMC Neurol. 2026 Jun 3. doi: 10.1186/s12883-026-05028-8. Online ahead of print.
35332216	Derived	Kuruvilla DE, Mann JI, Tepper SJ, Starling AJ, Panza G, Johnson MAL. Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM). Sci Rep. 2022 Mar 24;12(1):5110. doi: 10.1038/s41598-022-09071-6.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 26, 2018

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000259 BG001279 BG002538

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00066 OG00151

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.

Posted

Count of Participants

Participants

2 hours

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Count of Participants

Participants

2 hours

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Count of Participants

Participants

2 hours

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Count of Participants

Participants

2-24 hours

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts

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.

Posted

Count of Participants

Participants

24 hours

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Count of Participants

Participants

2-24 hours

ID	Title	Description
OG000	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.
OG001	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	298	0	298	22	259
EG001	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.	0	303	1	303	8	279

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Appendicitis leading to appendectomy	Surgical and medical procedures		Non-systematic Assessment	This Serious Adverse Event was not related to the subject's participation in the study and was not reportable neither to the Institutional Review Board (IRB) nor to the FDA (the subject did not apply the treatment).	EG0000 events0 affected298 at risk EG0011 events1 affected303 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Forehead paresthesias, discomfort, or burning	Nervous system disorders	Non-systematic Assessment	Expected side effect of the Cefaly® device	EG0009 events9 affected259 at risk EG0011 events1 affected279 at risk
Nausea / Vomiting	Nervous system disorders	Non-systematic Assessment		EG0004 events4 affected259 at risk EG0010 events0 affected279 at risk
Dizziness	Nervous system disorders	Non-systematic Assessment		EG0001 events1 affected259 at risk EG0012 events2 affected279 at risk
Neck Stiffness / Muscle tension	Nervous system disorders	Non-systematic Assessment		EG0001 events1 affected259 at risk EG0012 events2 affected279 at risk
Worsened Headache	Nervous system disorders	Non-systematic Assessment		EG0002 events2 affected259 at risk EG0010 events0 affected279 at risk
Orodynia - tooth or jaw pain	Skin and subcutaneous tissue disorders	Non-systematic Assessment		EG0001 events1 affected259 at risk EG0011 events1 affected279 at risk
Restlessness	Nervous system disorders	Non-systematic Assessment		EG0001 events1 affected259 at risk EG0011 events1 affected279 at risk
Abdominal Discomfort or Cramping	Ear and labyrinth disorders	Non-systematic Assessment		EG0000 events0 affected259 at risk EG0012 events2 affected279 at risk
Dry Mouth	Nervous system disorders	Non-systematic Assessment		EG0001 events1 affected259 at risk EG0010 events0 affected279 at risk
Excessive Sweating	Nervous system disorders	Non-systematic Assessment		EG0002 events2 affected259 at risk EG0010 events0 affected279 at risk
Sleepiness / Sedation	Nervous system disorders	Non-systematic Assessment		EG0001 events1 affected259 at risk EG0010 events0 affected279 at risk

ID	Term
D008881	Migraine Disorders

ID	Term
D051270	Headache Disorders, Primary
D020773	Headache Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases