Persistent Post Traumatic HeadachePhase 2NCT07624279
nVNS, CBD, and SoC for Persistent Post-Traumatic Headache
A Phase 2 study testing Non-Invasive Vagus Nerve Stimulation and Cannabidiol in people with Persistent Post Traumatic Headache, run by American Society of Pain and Neuroscience, Inc. at 8 sites in United States.
Trial summary
Do cannabidiol (CBD) or vagus nerve stimulation reduce the frequency of persistent post-traumatic headache more than traditional oral headache medications? Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Persistent Post Traumatic Headache
- What is being tested?
- Non-Invasive Vagus Nerve Stimulation and Cannabidiol
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 8 sitesUnited States
- Study dates
- 1 Jun 2026to 1 Jul 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.)
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
United States8 sites
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Melinda Lawrence, MD, melinda.lawrence@uhhospitals.org
Melinda Lawrence, MD
University of Kansas Medical Center
Kansas City, Kansas, 66160
Dawood Sayed, MD, dsayed1@yahoo.com
Dawood Sayed, MD
Kerlan-Jobe Orthopaedic Institute
Los Angeles, California, 90045
Vernon Williams, MD, vernon.williams@cskerlanjobe.org
Vernon Williams, MD
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
Boyle Cheng, PhD, boyle.cheng@ahn.org
Boyle Cheng, PhD
Mayo Clinic
Scottsdale, Arizona, 85054
Natalie Strand, MD, Strand.Natalie@mayo.edu
Natalie Strand, MD
Premier Pain Center
Shrewsbury, New Jersey, 07702
Katie Gee, 732-380-0200 ext. 65509, kgee@treatingpain.com
Sean Li, MD
Florida Spine & Pain Specialists
Tampa, Florida, 33614
Nomen Azeem, MD, azeemnx@gmail.com
Nomen Azeem, MD
International Spine, Pain & Performance Center
Washington D.C., District of Columbia, 20006
Mary Meg Valentine, BS, 202-849-8333, mvalentine@isppcenter.com
Mehul Desai, MD
About this study
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
Do cannabidiol (CBD) or vagus nerve stimulation reduce the frequency of persistent post-traumatic headache more than traditional oral headache medications?
Read the 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.
- Conditions
- Persistent Post Traumatic Headache
- Being tested
- Non-Invasive Vagus Nerve Stimulation, Cannabidiol, Standard of Care
- Keywords
- Persistent Post-Traumatic Headache, Vagus Nerve, Neuromodulation, Cannabidiol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-Invasive Vagus Nerve StimulationDevice
Also called gammaCore
Two treatments to the cervical vagus nerve twice daily
CannabidiolDrug
Also called BRC-003
Dosage titrated as per schedule
Standard of CareDrug
Oral pharmacotherapy as selected by site investigator and participant
| Study group | Role | What they receive |
|---|---|---|
| Non-Invasive Vagus Nerve Stimulation | Experimental | Not described Receives: Device: Non-Invasive Vagus Nerve Stimulation |
| Cannabidiol | Experimental | Not described Receives: Drug: Cannabidiol |
| Standard of Care | Experimental | Not described Receives: Drug: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Moderate-severe headache days
Mean reduction from baseline in number of moderate or severe headache days per 28 days during weeks 9-12
Measured: Weeks 9-12
Secondary outcomes (3)
50% Responder Rate
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
Measured: Weeks 9-12
Headache days
Mean reduction from baseline in number of headache days per 28 days during weeks 9-12
Measured: Weeks 9-12
Acute headache medication days
Mean reduction from baseline in number of days that acute medication was used per 28 days during weeks 9-12
Measured: Weeks 9-12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2026
- Study start1 Jun 2026 (estimated)
- Primary completion31 Jul 2027 (estimated)
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Persistent Post Traumatic HeadacheStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- American Society of Pain and Neuroscience, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- National Football League
- Responsible party
- Sponsor
- Investigators
- Nathaniel M Schuster, MD, Principal investigator, University of California, San DiegoErika A Petersen, MD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07624279
- Sponsor's protocol ID
- ASPN-NFL-US-1
- Status last verified
- May 2026
- First submitted
- 29 May 2026
- Last updated
- 3 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07624279
- Acronym / sponsor ID
- ASPN-NFL-US-1
- Conditions
- Persistent Post Traumatic Headache
- Keywords
- Persistent Post-Traumatic Headache, Vagus Nerve, Neuromodulation, Cannabidiol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- American Society of Pain and Neuroscience, Inc.University, hospital or other
- Collaborators
- National Football League
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 1 Jul 2028 (estimated)
- First posted
- 3 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Non-Invasive Vagus Nerve Stimulation | Experimental | Device: Non-Invasive Vagus Nerve Stimulation |
| Cannabidiol | Experimental | Drug: Cannabidiol |
| Standard of Care | Experimental | Drug: Standard of Care |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-Invasive Vagus Nerve StimulationAlso: gammaCoreTwo treatments to the cervical vagus nerve twice daily | Device | Non-Invasive Vagus Nerve Stimulation |
| CannabidiolAlso: BRC-003Dosage titrated as per schedule | Drug | Cannabidiol |
| Standard of CareOral pharmacotherapy as selected by site investigator and participant | Drug | Standard of Care |
Primary outcome
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
3 secondary outcomes
50% Responder Rate
Time frame: Weeks 9-12
Headache days
Time frame: Weeks 9-12
Acute headache medication days
Time frame: Weeks 9-12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nathaniel M Schuster, MD principal investigator
University of California, San Diego
Erika A Petersen, MD principal investigator
University of Arkansas
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Non-Invasive Vagus Nerve Stimulation and Cannabidiol in people with Persistent Post Traumatic Headache, run by American Society of Pain and Neuroscience, Inc. at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nathaniel M Schuster, MD ((858) 249-3800, nmschuster@health.ucsd.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Moderate-severe headache days (time frame: Weeks 9-12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.