nVNS, CBD, and SoC for Persistent Post-Traumatic Headache

Official title

A Phase 2 Randomized, Multicenter Study of Non-Invasive Vagus Nerve Stimulation (nVNS), Cannabidiol, and Standard of Care for the Treatment of Persistent Post-Traumatic Headache in Elite Athletes

Overview

Do cannabidiol (CBD) or vagus nerve stimulation reduce the frequency of persistent post-traumatic headache more than traditional oral headache medications?

Detailed description

In this randomized, open-label clinical trial, athletes with persistent post-traumatic headache will be treated with either non-invasive vagal nerve stimulation, cannabidiol, or standard of care oral pharmacotherapy for 12 weeks.

Interventions

• Device Non-Invasive Vagus Nerve Stimulation
  Two treatments to the cervical vagus nerve twice daily
• Drug Cannabidiol
  Dosage titrated as per schedule
• Drug Standard of Care
  Oral pharmacotherapy as selected by site investigator and participant

Primary outcome measures

• Moderate-severe headache days [Time frame: Weeks 9-12]

Secondary outcome measures (3)

• 50% Responder Rate [Time frame: Weeks 9-12]
• Headache days [Time frame: Weeks 9-12]
• Acute headache medication days [Time frame: Weeks 9-12]

Eligibility criteria

Inclusion criteria

• Between the ages of 18 and 75 years inclusive
• Participated in competitive sports at high school level or beyond or, in the case of sports without interscholastic competition, as per investigator
• Persistent headache attributed to traumatic injury to the head in accordance with the ICHD-3 criteria (including "Headache persists for >3 months after its onset")
• Experiences 4-25 (inclusive) headaches days per month (during the 28-day baseline period), with at least 4 of them being moderate or severe in intensity
• Completed at least 80% (23 of 28 days) on 28-day baseline headache diary
• Agrees to refrain from initiating or changing the type, dosage, or frequency of any preventive headache medications whether for headache prevention or for indications other than headache that, in the opinion of the clinician may interfere with the study objectives (e.g., antidepressants, anticonvulsants, beta-adrenergic blockers, etc.)
• Agrees to be randomized to nVNS, CBD or SoC
• Agrees to use nVNS, CBD, or SoC as intended, follow all of the requirements of the study including Follow-up Visit requirements, and record required study data in the subject e-diary
• Able to provide written informed consent

Exclusion criteria

• Body weight at screening of less than 40 kg
• Other severe pain condition (e.g., cancer pain or trigeminal neuralgia) that, in the discretion 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), neurologic disease (history of intracranial aneurysm, intracranial hemorrhage, or brain tumor), moderate to severe hepatic impairment, history of cervical surgery (e.g. cervical vagotomy) that in the judgment of the investigator would interfere with the study, or other major medical problems at the discretion of the investigator
• Psychiatric, substance abuse, or cognitive disorder and/or behavioral problems that, in the opinion of the investigator, may interfere with the study.
• Belongs to a vulnerable population (e.g., developmentally disabled, prisoner) or has any condition such that his or her ability to provide informed consent, comply with the follow-up requirements, or provide self-assessments is compromised at the discretion of the investigator
• Currently takes prescription opioids more than 4 days per month for any indication
• Patients receiving PREEMPT protocol onabotulinumtoxin injections, nerve blocks (occipital or other), steroid injections, radiofrequency ablations, and/or trigger point injections in the head or neck injections within the prior 12 weeks must continue receiving this procedure on a regular schedule at the discretion of the investigator during the course of the study. Patients who experience "wear-off" effects or increases in headache days during the last two weeks of their procedural cycles will be excluded from the study
• Currently implanted with a cardiac defibrillator
• Allergy to CBD or other components of Cannabis sativa L. (including hemp or cannabis)
• Previously used gammaCore or high-dose CBD (>100mg/day) for PPTH
• Used medical marijuana, cannabis, hemp or CBD-based product within 30 days prior to the study
• Unwilling to discontinue use of medical marijuana, cannabis, hemp or CBD-based product during the study
• Patients using medications that can interact with the study drug and/or its safety profile throughout the study and for at least five half-lives after the last dose of investigational product, including clobazam and valproic acid and other drugs according to the drug-drug interaction (DDI) risks as described in the Epidiolex USPI.
• Patients who are pregnant, breastfeeding, or not using acceptable methods of contraception during the course of the study and for three months thereafter.
• Male patient's partner is of childbearing potential; unless willing to ensure that they (male patients) or their partner(s) are using acceptable methods of contraception during the course of the study and for three months thereafter.
• Participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days
• A relative of or an employee of the Investigator or the clinical study site
• Presence of any implantable device that may interfere or interact with gammaCore, any history of cardiac arrhythmias or conduction defects, and any other medical history that, in the opinion of the investigator and/or based on the labeling of gammaCore, may increase the risk of using the gammaCore device.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• Mayo Clinic — Scottsdale
• Kerlan-Jobe Orthopaedic Institute — Los Angeles
• International Spine, Pain & Performance Center — Washington D.C.
• Florida Spine & Pain Specialists — Tampa
• University of Kansas Medical Center — Kansas City
• Premier Pain Center — Shrewsbury
• University Hospitals Cleveland Medical Center — Cleveland
• Allegheny General Hospital — Pittsburgh

Identifiers

NCT: NCT07624279 · ASPN-NFL-US-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗