Post-Traumatic HeadacheNCT04369729
Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache
An observational study of Post-Traumatic Headache, run by Mayo Clinic at 5 sites in United States.
Trial summary
This is a United States Department of Defense funded Focused Program study that aims to identify mechanisms and predictors for persistent of post-traumatic headache attributed to mild traumatic brain injury, and identify methods of preventing post-traumatic headache persistence Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Post-Traumatic Headache
- How many people
- 101 participants
- Where
- 5 sitesUnited States
- Study dates
- 9 Sep 2020to 31 Aug 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Study participants will be enrolled from the Mayo Clinic and Phoenix VA Healthcare System and from the surrounding region
Who may be able to join
- Have a diagnosis of acute PTH attributed to mild traumatic injury to the head as defined by the International Classification of Headache Disorders (ICHD-3).
- PTH onset 7-56 days prior to the time of enrollment.
- Adults 18-70 years of age.
- Willing to maintain a headache diary.
- Willing and able to return for follow-up visits.
- Adults 18-70 years of age.
- Willing and able to return for follow-up visits.
Who cannot join
- Chronic headache (i.e. at least 15 headache days/month for more than 3 months) within 12 months prior to the mTBI that led to the current PTH, including PPTH, chronic migraine, medication overuse headache, new daily persistent headache, hemicrania continua, chronic tension-type headache.
- Diminished decision-making capacity that in the investigator's opinion would interfere with the person's ability to provide informed consent and complete study procedures.
- Started or changed dose of a headache preventive medication within the 3 months prior to screening.
- Use of onabotulinumtoxinA in the head, neck or face region within 6 months of screening.
- During the 6 months before screening, use of opioids or barbiturates on at least 4 days per month.
- Subjects who underwent an intervention or used a device (e.g., nerve blocks, transcranial magnetic stimulation, vagal nerve stimulation, or electrical trigeminal nerve stimulation) for headache.
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- History of major psychiatric disorder such as schizophrenia and bipolar disorder.
- History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
- History of positive neuroimaging findings that indicate a moderate or severe TBI.
- Contraindications to magnetic resonance imaging, including, but not limited to (only for those individuals participating in the MRI portion of this research):
- Metal implants
- Aneurysm clips
- Severe claustrophobia
- Implanted electronic devices
- Insulin or infusion pump
- Cochlear/otologic/ear implant
- Non-removable prosthesis
- Implanted shunts/catheters
- Certain intrauterine devices
- Tattooed makeup
- Body piercings that cannot be removed
- Metal fragments
- Wire sutures or metal staples
- Factors that reduce MR image quality and interpretability (only for those individuals participating in the MRI portion of this research):
- Dental braces or other non-removable devices (e.g., retainers)
- Prior brain surgery
- Known brain MRI abnormality that in the investigator's opinion will significantly impact MRI data.
- Sensory disorders that in the investigator's opinion might affect perception of cutaneous thermal stimuli (e.g., peripheral neuropathy) (only for those individuals undergoing pain threshold testing).
- Pregnancy
- Breastfeeding
- Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study.
- HEALTHY CONTROL ELIGIBILITY CRITERIA
- History of traumatic brain injury.
- History of migraine or other headaches (Tension-type headache up to an average of 3 days per month is allowed).
- Diminished decision-making capacity that in the investigator's opinion would interfere with the person's ability to provide informed consent and complete study procedures.
- During the 6 months before screening, use of opioids or barbiturates on an average of at least 4 days per month.
- History of major psychiatric disorder such as schizophrenia and bipolar disorder.
- History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
- Contraindications to magnetic resonance imaging, including, but not limited to:
- Metal implants
- Aneurysm clips
- Severe claustrophobia
- Implanted electronic devices
- Insulin or infusion pump
- Cochlear/otologic/ear implant
- Non-removable prosthesis
- Implanted shunts/catheters
- Certain intrauterine devices
- Tattooed makeup
- Body piercings that cannot be removed
- Metal fragments
- Wire sutures or metal staples
- Factors that reduce MR image quality and interpretability:
- Dental braces or other non-removable devices (e.g., retainers)
- Prior brain surgery
- Known brain MRI abnormality that in the investigator's opinion will significantly impact MRI data.
- Sensory disorders that in the investigator's opinion might affect perception of cutaneous thermal stimuli (e.g., peripheral neuropathy).
- Pregnancy
- Breastfeeding
- Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study
- Has previously received any CGRP ligand or receptor targeted monoclonal antibody
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Mayo Clinic
Jacksonville, Florida, 32224
Phoenix VA Health Care System
Phoenix, Arizona, 85012
Mayo Clinic
Phoenix, Arizona, 85054
Mayo Clinic
Rochester, Minnesota, 55901
Mayo Clinic
Scottsdale, Arizona, 85259
About this study
Official title: A Multidisciplinary Translational Approach to Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache - Human Studies Protocol: Individual Projects Excluding Clinical Trial
This is a United States Department of Defense funded Focused Program study that aims to identify mechanisms and predictors for persistent of post-traumatic headache attributed to mild traumatic brain injury, and identify methods of preventing post-traumatic headache persistence
Read the detailed description
The human studies component of this Focused Program include clinical phenotyping, neurophysiology, molecular and genetic biomarker discovery, and brain imaging. This data will be utilized to characterize post-traumatic headache and build univariate and multivariate predictive models for post-traumatic headache persistence and for the response to post-traumatic headache treatment. Some participants might be eligible to participate in the clinical trial portion of this study.The clinical trial is a double-blind, randomized, placebo-controlled investigation of erenumab for the treatment of post-traumatic headache. Participants will be randomized when PTH has been present for 35-56 days. The clinical trial component of this Focused Program is described in more detail in a separate clinicaltrials.gov record.
Follow-up questionnaires, headache diary data, pain threshold results, and brain imaging data will be collected longitudinally during the trial to assess for changes over time and associations of such changes with post-traumatic headache treatment outcomes.
- Conditions
- Post-Traumatic Headache
- Medical subject headings
- Post-Traumatic Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Post-Traumatic Headache | Individuals who have post-traumatic headache attributed to mild traumatic brain injury according to ICHD-3 diagnostic criteria | |
| Healthy Control | Healthy controls will have no history of traumatic brain injury and no history of migraine or other headaches |
What is being measured
The primary outcome is the main question the study is designed to answer.
Longitudinal Assessment of PTH Phenotype
descriptive analysis of post-traumatic headache characteristics such as headache frequency and severity, and characteristics of associated conditions such as symptoms of sensory hypersensitivities, anxiety, depression, insomnia, autonomic dysfunction, and cognitive function
Measured: baseline with longitudinal follow-up at weeks four and sixteen
Longitudinal Assessment of Cutaneous Pain Thresholds
heat pain thresholds on the skin determined by quantitative sensory testing
Measured: baseline with longitudinal follow-up at weeks four and sixteen
Longitudinal Assessment of Visual Pain Thresholds from Bright Light Exposure
visual pain thresholds to different light intensities
Measured: baseline with longitudinal follow-up at weeks four and sixteen
Longitudinal Assessment of Brain MRI
structural brain imaging to include measures such as cortical thickness, regional volumes, brain curvature, white matter tract integrity, and functional brain imaging measures such as resting state functional connectivity and pain-induced brain activation
Measured: baseline with longitudinal follow-up at weeks four and sixteen
Longitudinal Assessment of Blood Based Biomarkers
blood-based biomarkers, including DNA and targeted serum proteins, associated with acute and persistent post-traumatic headache and response to therapy
Measured: baseline with longitudinal follow-up at weeks four and sixteen
Longitudinal Assessment of Post-traumatic Headache Biomarkers
clinical characteristics, pain thresholds, and brain imaging features as described above that are associated with acute post-traumatic headache and persistent post-traumatic headache; that predict the persistent of post-traumatic headache; and that predict and measure treatment response
Measured: baseline with longitudinal follow-up at weeks four and sixteen
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2020
- Study start9 Sep 2020
- Primary completion31 Aug 2025
- Study completion31 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-Traumatic HeadacheStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- University of Arizona, Translational Genomics Research Institute, Arizona State University, Phoenix VA Health Care System, United States Department of Defense, Amgen
- Responsible party
- Principal investigator, Todd J. Schwedt, Mayo Clinic
- Investigators
- Todd Schwedt, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04369729
- Sponsor's protocol ID
- 20-003732
- Status last verified
- Sep 2025
- First submitted
- 25 Apr 2020
- Last updated
- 12 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multidisciplinary Translational Approach to Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache - Human Studies Protocol: Individual Projects Excluding Clinical Trial
- ClinicalTrials.gov ID
- NCT04369729
- Acronym / sponsor ID
- 20-003732
- Conditions
- Post-Traumatic Headache
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- University of Arizona, Translational Genomics Research Institute, Arizona State University, Phoenix VA Health Care System, United States Department of Defense, Amgen
- Study start
- 9 Sep 2020 (actual)
- Primary completion
- 31 Aug 2025 (actual)
- Study completion
- 31 Aug 2025 (actual)
- First posted
- 30 Apr 2020 (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.
This is a United States Department of Defense funded Focused Program study that aims to identify mechanisms and predictors for persistent of post-traumatic headache attributed to mild traumatic brain injury, and identify methods of preventing post-traumatic headache persistence
Detailed description
The human studies component of this Focused Program include clinical phenotyping, neurophysiology, molecular and genetic biomarker discovery, and brain imaging. This data will be utilized to characterize post-traumatic headache and build univariate and multivariate predictive models for post-traumatic headache persistence and for the response to post-traumatic headache treatment. Some participants might be eligible to participate in the clinical trial portion of this study.The clinical trial is a double-blind, randomized, placebo-controlled investigation of erenumab for the treatment of post-traumatic headache. Participants will be randomized when PTH has been present for 35-56 days. The clinical trial component of this Focused Program is described in more detail in a separate clinicaltrials.gov record.
Follow-up questionnaires, headache diary data, pain threshold results, and brain imaging data will be collected longitudinally during the trial to assess for changes over time and associations of such changes with post-traumatic headache treatment outcomes.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Post-Traumatic Headache | – | –Individuals who have post-traumatic headache attributed to mild traumatic brain injury according to ICHD-3 diagnostic criteria |
| Healthy Control | – | –Healthy controls will have no history of traumatic brain injury and no history of migraine or other headaches |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Study participants will be enrolled from the Mayo Clinic and Phoenix VA Healthcare System and from the surrounding region
Key inclusion criteria (7 listed)
- Have a diagnosis of acute PTH attributed to mild traumatic injury to the head as defined by the International Classification of Headache Disorders (ICHD-3).
- PTH onset 7-56 days prior to the time of enrollment.
- Adults 18-70 years of age.
- Willing to maintain a headache diary.
- Willing and able to return for follow-up visits.
Key exclusion criteria (61 listed)
- Chronic headache (i.e. at least 15 headache days/month for more than 3 months) within 12 months prior to the mTBI that led to the current PTH, including PPTH, chronic migraine, medication overuse headache, new daily persistent headache, hemicrania continua, chronic tension-type headache.
- Diminished decision-making capacity that in the investigator's opinion would interfere with the person's ability to provide informed consent and complete study procedures.
- Started or changed dose of a headache preventive medication within the 3 months prior to screening.
- Use of onabotulinumtoxinA in the head, neck or face region within 6 months of screening.
- During the 6 months before screening, use of opioids or barbiturates on at least 4 days per month.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Longitudinal Assessment of PTH Phenotype
Time frame: baseline with longitudinal follow-up at weeks four and sixteen
descriptive analysis of post-traumatic headache characteristics such as headache frequency and severity, and characteristics of associated conditions such as symptoms of sensory hypersensitivities, anxiety, depression, insomnia, autonomic dysfunction, and cognitive function
Longitudinal Assessment of Cutaneous Pain Thresholds
Time frame: baseline with longitudinal follow-up at weeks four and sixteen
heat pain thresholds on the skin determined by quantitative sensory testing
Longitudinal Assessment of Visual Pain Thresholds from Bright Light Exposure
Time frame: baseline with longitudinal follow-up at weeks four and sixteen
visual pain thresholds to different light intensities
Longitudinal Assessment of Brain MRI
Time frame: baseline with longitudinal follow-up at weeks four and sixteen
structural brain imaging to include measures such as cortical thickness, regional volumes, brain curvature, white matter tract integrity, and functional brain imaging measures such as resting state functional connectivity and pain-induced brain activation
Longitudinal Assessment of Blood Based Biomarkers
Time frame: baseline with longitudinal follow-up at weeks four and sixteen
blood-based biomarkers, including DNA and targeted serum proteins, associated with acute and persistent post-traumatic headache and response to therapy
Longitudinal Assessment of Post-traumatic Headache Biomarkers
Time frame: baseline with longitudinal follow-up at weeks four and sixteen
clinical characteristics, pain thresholds, and brain imaging features as described above that are associated with acute post-traumatic headache and persistent post-traumatic headache; that predict the persistent of post-traumatic headache; and that predict and measure treatment response
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2025.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Todd Schwedt principal investigator
Mayo Clinic
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Post-Traumatic Headache, run by Mayo Clinic at 5 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 7 inclusion and 61 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: finished, as of the sponsor's last update on 12 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Longitudinal Assessment of PTH Phenotype (time frame: baseline with longitudinal follow-up at weeks four and sixteen). The study lists 6 primary outcomes in all. 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 12 Sep 2025.