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

May 29, 2026 updated by: American Society of Pain and Neuroscience, Inc.

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85054
        • Mayo Clinic
        • Contact:
        • Principal Investigator:
          • Natalie Strand, MD
    • California
      • Los Angeles, California, United States, 90045
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20006
        • International Spine, Pain & Performance Center
        • Principal Investigator:
          • Mehul Desai, MD
        • Contact:
    • Florida
      • Tampa, Florida, United States, 33614
        • Florida Spine & Pain Specialists
        • Principal Investigator:
          • Nomen Azeem, MD
        • Contact:
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
        • Principal Investigator:
          • Dawood Sayed, MD
        • Contact:
    • New Jersey
      • Shrewsbury, New Jersey, United States, 07702
        • Premier Pain Center
        • Principal Investigator:
          • Sean Li, MD
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Cleveland Medical Center
        • Contact:
        • Principal Investigator:
          • Melinda Lawrence, MD
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
        • Principal Investigator:
          • Boyle Cheng, PhD
        • Principal Investigator:
          • Patrick DeMeo, MD
        • Contact:
        • Sub-Investigator:
          • Praveer Vyas, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA

  1. Between the ages of 18 and 75 years inclusive
  2. Participated in competitive sports at high school level or beyond or, in the case of sports without interscholastic competition, as per investigator
  3. 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")
  4. 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
  5. Completed at least 80% (23 of 28 days) on 28-day baseline headache diary
  6. 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.)
  7. Agrees to be randomized to nVNS, CBD or SoC
  8. 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
  9. Able to provide written informed consent

EXCLUSION CRITERIA

  1. Body weight at screening of less than 40 kg
  2. Other severe pain condition (e.g., cancer pain or trigeminal neuralgia) that, in the discretion of the investigator, may confound the study assessments
  3. 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
  4. Psychiatric, substance abuse, or cognitive disorder and/or behavioral problems that, in the opinion of the investigator, may interfere with the study.
  5. 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
  6. Currently takes prescription opioids more than 4 days per month for any indication
  7. 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
  8. Currently implanted with a cardiac defibrillator
  9. Allergy to CBD or other components of Cannabis sativa L. (including hemp or cannabis)
  10. Previously used gammaCore or high-dose CBD (>100mg/day) for PPTH
  11. Used medical marijuana, cannabis, hemp or CBD-based product within 30 days prior to the study
  12. Unwilling to discontinue use of medical marijuana, cannabis, hemp or CBD-based product during the study
  13. 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.
  14. Patients who are pregnant, breastfeeding, or not using acceptable methods of contraception during the course of the study and for three months thereafter.
  15. 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.
  16. Participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days
  17. A relative of or an employee of the Investigator or the clinical study site
  18. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cannabidiol
Drug: Cannabidiol
Dosage titrated as per schedule
Other Names:
  • BRC-003
Experimental: Non-Invasive Vagus Nerve Stimulation
Device: Non-Invasive Vagus Nerve Stimulation
Two treatments to the cervical vagus nerve twice daily
Other Names:
  • gammaCore
Experimental: Standard of Care
Drug: Standard of Care
Oral pharmacotherapy as selected by site investigator and participant

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Moderate-severe headache days
Time Frame: Weeks 9-12
Mean reduction from baseline in number of moderate or severe headache days per 28 days during weeks 9-12
Weeks 9-12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
50% Responder Rate
Time Frame: Weeks 9-12
Percentage of participants who report at least a 50% reduction in the number of moderate or severe headache days per 28 days during the last 4 weeks versus the 4 week baseline period
Weeks 9-12
Headache days
Time Frame: Weeks 9-12
Mean reduction from baseline in number of headache days per 28 days during weeks 9-12
Weeks 9-12
Acute headache medication days
Time Frame: Weeks 9-12
Mean reduction from baseline in number of days that acute medication was used per 28 days during weeks 9-12
Weeks 9-12

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percent reduction in moderate or severe headache days
Time Frame: Weeks 9-12
Mean percent reduction from baseline in moderate or severe headache days per 28 days during weeks 9-12
Weeks 9-12
HIT-6
Time Frame: Weeks 9-12
Change from baseline in Headache Impact Test-6
Weeks 9-12
EQ-5D-5L
Time Frame: Weeks 9-12
Change from baseline in EQ-5D-5L
Weeks 9-12
PGIC
Time Frame: Weeks 9-12
Patient Global Impression of Change
Weeks 9-12
PROMIS-29
Time Frame: Week 12
Change from baseline in PROMIS-29
Week 12
Moderate-severe headache days
Time Frame: 1-4
Mean reduction from baseline in number of moderate or severe headache days per 28 days during weeks 1-4
1-4
Moderate-severe headache days
Time Frame: 5-8
Mean reduction from baseline in number of moderate or severe headache days per 28 days during weeks 5-8
5-8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
American Society of Pain and Neuroscience, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Football League

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Nathaniel M Schuster, MD, University of California, San Diego
  • Principal Investigator: Erika A Petersen, MD, University of Arkansas

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 29, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 3, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ASPN-NFL-US-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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