Phase 3 randomized, double-blind, sham-controlled Trial of e-TNS for the Acute treatment of Migraine (TEAM)

Abstract

Migraine is one of the most common and debilitating neurological disorders worldwide. External Trigeminal Nerve Stimulation (e-TNS) is a non-pharmacological, non-invasive therapeutic alternative for patients with migraine. The TEAM study was a prospective, multicenter, randomized, double-blind, sham-controlled, Phase 3 trial for 2-h, continuous, e-TNS treatment of a single moderate or severe migraine attack at home. A total of 538 adults meeting the International Classification of Headache Disorders 3rd edition criteria for 2-8 migraine headache days per month were recruited and randomized in a 1:1 ratio to 2-h active or sham stimulation. Migraine pain levels and most bothersome migraine-associated symptoms (MBS) were recorded at baseline, 2 h, and 24 h using a paper diary. The primary endpoints for the study were pain freedom at 2 h and freedom from the MBS at 2 h. The secondary endpoints were pain relief at 2 h, absence of most bothersome migraine-associated symptoms (MBSs) at 2 h, acute medication use within 24 h after treatment, sustained pain freedom at 24 h, and sustained pain relief at 24 h. Adverse event data was also collected and compared between groups. Five hundred thirty-eight patients were randomized to either the verum (n = 259) or sham (n = 279) group and were included in an intention-to-treat analysis. The percentage of patients with pain freedom at 2 h was 7.2% higher in verum (25.5%) compared to sham (18.3%; p = 0.043). Resolution of most bothersome migraine-associated symptom was 14.1% higher in verum (56.4%) compared to sham (42.3%; p = 0.001). With regards to secondary outcomes, pain relief at 2 h was 14.3% higher in verum (69.5%) than sham (55.2%; p = 0.001), absence of all migraine-associated symptoms at 2 h was 8.4% higher in verum (42.5%) than sham (34.1%; p = 0.044), sustained pain freedom and pain relief at 24 h was 7.0% and 11.5% higher in verum (22.8 and 45.9%) than sham (15.8 and 34.4%; p = 0.039 and .006, respectively). No serious adverse events were reported. Treatment with 2-h e-TNS is a safe and effective, non-invasive, and non-pharmacological alternative for the acute treatment of migraine attacks in an at-home setting.Trial registration Clinicaltrials.gov Identifier: NCT03465904. Registered 14/03/2018. https://www.clinicaltrials.gov/ct2/show/record/NCT03465904 .

Trial registration: ClinicalTrials.gov NCT02787551 NCT03465904 NCT02787551.

Conflict of interest statement

Dr. Deena Kuruvilla has received consulting fees from Amgen, Lily, Allergan, and GLG Consulting Group. Dr Joseph Mann has no conflicting interests. Dr. Stewart Tepper reports grants for research (no personal compensation) from Allergan/Abbvie, Amgen, Eli Lilly, Lundbeck, Neurolief, Novartis, Satsuma, and Zosano, consultant and/or Advisory Boards (honoraria) from Aeon, Allergan/Abbvie, Alphasights, Amgen, Atheneum, Axsome Therapeutics, Becker Pharmaceutical Consulting ClearView Healthcare Partners, CoolTech, CRG, Currax, DRG, Eli Lilly, ExpertConnect, FCB Health, GLG, Guidepoint Global, Health Science Communications, HMP Communications, Impel, InteractiveForums, Krog and Partners, Lundbeck, M3 Global Research, MJH Holdings, Neurolief, Novartis, Palion Medical, Pulmatrix, SAI MedPartners, Satsuma, Spherix Global Insights, Strategy Inc, System Analytic, Taylor and Francis, Teva, Theranica, Unity HA, XOC, and Zosano, salary from Dartmouth-Hitchcock Medical Center, American Headache Society, and Thomas Jefferson University, and CME honoraria from the American Academy of Neurology, American Headache Society, Catamount Medical Education, Diamond Headache Clinic, Forefront Collaborative, Haymarket Medical Education, Peerview, Medical Education Speakers Network, Migraine Association of Ireland, North American Center for CME, The Ohio State University, Physicians’ Education Resource, PlatformQ Education, Primed, Texas Neurological Society, and WebMD/Medscape. Dr. Amaal J. Starling has received consulting fees from Allergan, Amgen, Axsome Therapeutics, Eli Lilly & Company, Everyday Health, Impel, Lundbeck, Med-IQ, Medscape, Neurolief, Novartis, Satsuma, Teva, and Theranica Dr. Gregory Panza has no conflicting interests. Dr Michael A.L. Johnson is the Global Director of Medical Affairs for CEFALY Technology. All other authors do not have any competing interest.

© 2022. The Author(s).

Figures

Figure 1

Study design flowchart.

Figure 2

Patient enrollment and allocation.