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

NCT07624279 | Not Yet Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: ASPN-NFL-US-1
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 8

Brief Summary

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

Conditions

Persistent Post Traumatic Headache

Keywords

Persistent Post-Traumatic Headache, Vagus Nerve, Neuromodulation, Cannabidiol

Outcome Measures

Primary Outcomes (1)

• Moderate-severe headache days

  Mean reduction from baseline in number of moderate or severe headache days per 28 days during weeks 9-12

  Weeks 9-12

Secondary Outcomes (3)

• 50% Responder Rate

  Weeks 9-12

• Headache days

  Weeks 9-12

• Acute headache medication days

  Weeks 9-12

Other Outcomes (7)

• Percent reduction in moderate or severe headache days

  Weeks 9-12

• HIT-6

  Weeks 9-12

• EQ-5D-5L

  Weeks 9-12

Study Arms (3)

Non-Invasive Vagus Nerve Stimulation

EXPERIMENTAL

Device: Non-Invasive Vagus Nerve Stimulation

Cannabidiol

EXPERIMENTAL

Drug: Cannabidiol

Standard of Care

EXPERIMENTAL

Drug: Standard of Care

Interventions

Non-Invasive Vagus Nerve Stimulation DEVICE

Two treatments to the cervical vagus nerve twice daily

Also known as: gammaCore

Non-Invasive Vagus Nerve Stimulation

Cannabidiol DRUG

Dosage titrated as per schedule

Also known as: BRC-003

Cannabidiol

Standard of Care DRUG

Oral pharmacotherapy as selected by site investigator and participant

Standard of Care

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• American Society of Pain and Neuroscience, Inc.: lead
• National Football League: collaborator

Study Sites (8)

Mayo Clinic

Scottsdale, Arizona, 85054, United States

Location

Kerlan-Jobe Orthopaedic Institute

Los Angeles, California, 90045, United States

Location

International Spine, Pain & Performance Center

Washington D.C., District of Columbia, 20006, United States

Location

Florida Spine & Pain Specialists

Tampa, Florida, 33614, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Premier Pain Center

Shrewsbury, New Jersey, 07702, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

MeSH Terms

Interventions

Cannabidiol; Standard of Care

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Nathaniel M Schuster, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

• Erika A Petersen, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nathaniel M Schuster, MD

CONTACT

(858) 249-3800; nmschuster@health.ucsd.edu

Erika A Petersen

CONTACT

501-686-5270; eapetersen@uams.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2026
• First Posted: June 3, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: June 3, 2026

Record last verified: 2026-05

Locations

US (8)