Study of Gammacore Sapphire for the Acute and Preventive Treatment of Post-Traumatic Headache (GAP-PTH)

NCT04071743 | Withdrawn DMC FDA Device

• 1 other identifier: STU-2019-0933
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this single-center, prospective, randomized, double-blind, sham controlled, parallel-group study is to collect clinical data related to the safety and efficacy of vagus nerve stimulation for the acute and preventive treatment of Post Traumatic Headache.

Conditions

Post-Traumatic Headache

Outcome Measures

Primary Outcomes (1)

• Relief of Post Traumatic Headache

  Decrease in pain between active and sham treatment groups between the baseline assessment and 60 minutes post-treatment on a subset of questions from the Sport Concussion Assessment Tool, 5th edition (SCAT5) Graded Symptom Checklist

  Over 14 weeks

Secondary Outcomes (1)

• Decrease in Pain

  Over 14 weeks

Study Arms (2)

Treatment

ACTIVE COMPARATOR

Treatment and Prevention with active gammacore device(vagus nerve stimulator)

Device: gammaCore Sapphire

Sham

SHAM COMPARATOR

Treatment and Prevention with sham gammacore device(vagus nerve stimulator)

Device: sham gammaCore Sapphire

Interventions

gammaCore Sapphire DEVICE

non-invasive vagus nerve stimulator

Treatment

sham gammaCore Sapphire DEVICE

sham gammaCore Sapphire

Sham

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets the ICHD-3 criteria for acute headache attributed to mild traumatic injury to the head
• Experiences a minimum of 2 headaches (migraine or probable migraine phenotype) per week
• Presentation to clinic between 2 and 4 weeks after injury
• Able to provide written informed consent

You may not qualify if:

• Any pre-existing primary headache disorder (with the exception of infrequent episodic tension type headache)
• Any contraindication to using nVNS
• Initiation or change in the dosage of any medication commonly used or headache prophylaxis 3 months before enrollment into the study
• Continuous headache at the time of enrollment
• PTH \>4 weeks after injury
• Structural abnormality at the nVNS treatment site (e.g., lymphadenopathy, previous surgery, abnormal anatomy)
• Pain at the nVNS treatment site (e.g., dysesthesia, neuralgia, cervicalgia)
• Other significant pain problem (e.g., cancer pain, fibromyalgia, other head or facial pain disorder) that, in the opinion of the Investigator, may confound the study assessments
• Known or suspected severe cardiac disease (e.g., symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure) or an abnormal baseline electrocardiogram (ECG) within the last year (e.g., second- or third-degree heart block, prolonged QT interval, atrial fibrillation, atrial flutter, history of ventricular tachycardia or ventricular fibrillation, clinically significant premature ventricular contraction)
• Known or suspected cerebrovascular disease (e.g., prior stroke or transient ischemic attack, symptomatic carotid artery disease, prior carotid endarterectomy or other vascular neck surgery)
• Previous cervical vagotomy
• A relative of or an employee of the Investigator or the clinical study site
• Previously used gammaCore

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• ElectroCore INC: collaborator

Study Sites (1)

UT Southwestern Medical Center Dallas

Dallas, Texas, 75390-9044, United States

Location

Related Publications (26)

• Defrin R. Chronic post-traumatic headache: clinical findings and possible mechanisms. J Man Manip Ther. 2014 Feb;22(1):36-44. doi: 10.1179/2042618613Y.0000000053.

  PMID: 24976746 BACKGROUND

• DiTommaso C, Hoffman JM, Lucas S, Dikmen S, Temkin N, Bell KR. Medication usage patterns for headache treatment after mild traumatic brain injury. Headache. 2014 Mar;54(3):511-9. doi: 10.1111/head.12254.

  PMID: 24741687 BACKGROUND

• Lucas S. Posttraumatic Headache: Clinical Characterization and Management. Curr Pain Headache Rep. 2015 Oct;19(10):48. doi: 10.1007/s11916-015-0520-1.

  PMID: 26280569 BACKGROUND

• Bree D, Levy D. Development of CGRP-dependent pain and headache related behaviours in a rat model of concussion: Implications for mechanisms of post-traumatic headache. Cephalalgia. 2018 Feb;38(2):246-258. doi: 10.1177/0333102416681571. Epub 2016 Dec 7.

  PMID: 27899434 BACKGROUND

• Conidi FX. Interventional Treatment for Post-traumatic Headache. Curr Pain Headache Rep. 2016 Jun;20(6):40. doi: 10.1007/s11916-016-0570-z.

  PMID: 27130542 BACKGROUND

• Packard RC. Treatment of chronic daily posttraumatic headache with divalproex sodium. Headache. 2000 Oct;40(9):736-9. doi: 10.1046/j.1526-4610.2000.00128.x.

  PMID: 11091292 BACKGROUND

• Langdon R, Taraman S. Posttraumatic Headache. Pediatr Ann. 2018 Feb 1;47(2):e61-e68. doi: 10.3928/19382359-20180131-01.

  PMID: 29446796 BACKGROUND

• Elahi F, Reddy C. High cervical epidural neurostimulation for post-traumatic headache management. Pain Physician. 2014 Jul-Aug;17(4):E537-41.

  PMID: 25054404 BACKGROUND

• Schwedt TJ, Dodick DW, Hentz J, Trentman TL, Zimmerman RS. Occipital nerve stimulation for chronic headache--long-term safety and efficacy. Cephalalgia. 2007 Feb;27(2):153-7. doi: 10.1111/j.1468-2982.2007.01272.x.

  PMID: 17257236 BACKGROUND

• Elahi F, Reddy C. Neuromodulation of the great auricular nerve for persistent post-traumatic headache. Pain Physician. 2014 Jul-Aug;17(4):E531-6.

  PMID: 25054403 BACKGROUND

• Leung A, Fallah A, Shukla S, Lin L, Tsia A, Song D, Polston G, Lee R. rTMS in Alleviating Mild TBI Related Headaches--A Case Series. Pain Physician. 2016 Feb;19(2):E347-54.

  PMID: 26815263 BACKGROUND

• Leung A, Metzger-Smith V, He Y, Cordero J, Ehlert B, Song D, Lin L, Shahrokh G, Tsai A, Vaninetti M, Rutledge T, Polston G, Sheu R, Lee R. Left Dorsolateral Prefrontal Cortex rTMS in Alleviating MTBI Related Headaches and Depressive Symptoms. Neuromodulation. 2018 Jun;21(4):390-401. doi: 10.1111/ner.12615. Epub 2017 May 30.

  PMID: 28557049 BACKGROUND

• Howland RH. Vagus Nerve Stimulation. Curr Behav Neurosci Rep. 2014 Jun;1(2):64-73. doi: 10.1007/s40473-014-0010-5.

  PMID: 24834378 BACKGROUND

• Yuan H, Silberstein SD. Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part I. Headache. 2016 Jan;56(1):71-8. doi: 10.1111/head.12647. Epub 2015 Sep 14.

  PMID: 26364692 BACKGROUND

• Schachter SC. Vagus nerve stimulation therapy summary: five years after FDA approval. Neurology. 2002 Sep 24;59(6 Suppl 4):S15-20. doi: 10.1212/wnl.59.6_suppl_4.s15.

  PMID: 12270963 BACKGROUND

• Cecchini AP, Mea E, Tullo V, Curone M, Franzini A, Broggi G, Savino M, Bussone G, Leone M. Vagus nerve stimulation in drug-resistant daily chronic migraine with depression: preliminary data. Neurol Sci. 2009 May;30 Suppl 1:S101-4. doi: 10.1007/s10072-009-0073-3.

  PMID: 19415436 BACKGROUND

• Mauskop A. Vagus nerve stimulation relieves chronic refractory migraine and cluster headaches. Cephalalgia. 2005 Feb;25(2):82-6. doi: 10.1111/j.1468-2982.2005.00611.x.

  PMID: 15658944 BACKGROUND

• Follesa P, Biggio F, Gorini G, Caria S, Talani G, Dazzi L, Puligheddu M, Marrosu F, Biggio G. Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain. Brain Res. 2007 Nov 7;1179:28-34. doi: 10.1016/j.brainres.2007.08.045. Epub 2007 Aug 25.

  PMID: 17920573 BACKGROUND

• Korley FK, Diaz-Arrastia R, Wu AH, Yue JK, Manley GT, Sair HI, Van Eyk J, Everett AD; TRACK-TBI investigators; Okonkwo DO, Valadka AB, Gordon WA, Maas AI, Mukherjee P, Yuh EL, Lingsma HF, Puccio AM, Schnyer DM. Circulating Brain-Derived Neurotrophic Factor Has Diagnostic and Prognostic Value in Traumatic Brain Injury. J Neurotrauma. 2016 Jan 15;33(2):215-25. doi: 10.1089/neu.2015.3949. Epub 2015 Sep 18.

  PMID: 26159676 BACKGROUND

• Wurzelmann M, Romeika J, Sun D. Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury. Neural Regen Res. 2017 Jan;12(1):7-12. doi: 10.4103/1673-5374.198964.

  PMID: 28250730 BACKGROUND

• Acheson A, Conover JC, Fandl JP, DeChiara TM, Russell M, Thadani A, Squinto SP, Yancopoulos GD, Lindsay RM. A BDNF autocrine loop in adult sensory neurons prevents cell death. Nature. 1995 Mar 30;374(6521):450-3. doi: 10.1038/374450a0.

  PMID: 7700353 BACKGROUND

• Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677-736. doi: 10.1146/annurev.neuro.24.1.677.

  PMID: 11520916 BACKGROUND

• Neren D, Johnson MD, Legon W, Bachour SP, Ling G, Divani AA. Vagus Nerve Stimulation and Other Neuromodulation Methods for Treatment of Traumatic Brain Injury. Neurocrit Care. 2016 Apr;24(2):308-19. doi: 10.1007/s12028-015-0203-0.

  PMID: 26399249 BACKGROUND

• Lamb DG, Porges EC, Lewis GF, Williamson JB. Non-invasive Vagal Nerve Stimulation Effects on Hyperarousal and Autonomic State in Patients with Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury: Preliminary Evidence. Front Med (Lausanne). 2017 Jul 31;4:124. doi: 10.3389/fmed.2017.00124. eCollection 2017.

  PMID: 28824913 BACKGROUND

• Silberstein SD, Calhoun AH, Lipton RB, Grosberg BM, Cady RK, Dorlas S, Simmons KA, Mullin C, Liebler EJ, Goadsby PJ, Saper JR; EVENT Study Group. Chronic migraine headache prevention with noninvasive vagus nerve stimulation: The EVENT study. Neurology. 2016 Aug 2;87(5):529-38. doi: 10.1212/WNL.0000000000002918. Epub 2016 Jul 13.

  PMID: 27412146 BACKGROUND

• Tassorelli C, Grazzi L, de Tommaso M, Pierangeli G, Martelletti P, Rainero I, Dorlas S, Geppetti P, Ambrosini A, Sarchielli P, Liebler E, Barbanti P; PRESTO Study Group. Noninvasive vagus nerve stimulation as acute therapy for migraine: The randomized PRESTO study. Neurology. 2018 Jul 24;91(4):e364-e373. doi: 10.1212/WNL.0000000000005857. Epub 2018 Jun 15.

  PMID: 29907608 BACKGROUND

MeSH Terms

Conditions

Post-Traumatic Headache

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: August 28, 2019
• Study Start: January 1, 2020
• Primary Completion: September 1, 2021
• Study Completion: December 31, 2021
• Last Updated: March 10, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)