Post-Traumatic HeadachePhase 2NCT04098250
Multidisciplinary Translational Approach to Investigate Mechanisms Predictors & Prevention of Persistent PTH
A Phase 2 study testing Erenumab in people with 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 years
- Conditions the study is for
- Post-Traumatic Headache
- What is being tested?
- Erenumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 5 sitesUnited States
- Study dates
- 4 Jan 2021to 10 Jan 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- No healthy volunteers
- Adult, Older adult
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 be randomized to either of the two clinical trial treatment arms
- Willing to maintain a headache diary
- Willing and able to return for follow-up visits
- 4 or more moderate or severe headache days during the 4-week run-in phase and an increase of at least 2 moderate to severe headache days compared to pre-TBI and at least a 30% increase
- At least 80% compliant with diary keeping during the 4-week run-in phase (i.e., provides data on at least 80% of days)
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 an average of 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 within 3 months of screening
Show all 40Show fewer
- 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 an exclusion for patients participating in the brain MRI portion of this research):
- Metal implants
- Aneurysm clips
- Severe claustrophobia
- Implanted electronic device
- 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 an exclusion for patients participating in the brain 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 an exclusion for patients participating in the neurophysiology studies)
- Pregnancy
- Breastfeeding
- History of myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months prior to screening.
- Not willing to use a reliable form of contraception (for women of childbearing potential) through 16 weeks after the last dose of erenumab. Acceptable methods of birth control include not having intercourse, hormonal birth control methods, intrauterine devices, surgical contraceptive methods, or two barrier methods (each partner must use a barrier method) with spermicide. A reliable form of contraception must be started prior to or at the time of starting the run-in phase. Not being of childbearing potential is defined as any woman who is post-menopausal by history, defined as:
- At least 55 years of age with cessation of menses for 12 or more months; OR
- Younger than 55 years of age but no spontaneous menses for at least 2 years; OR
- Younger than 55 years of age and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels at least 40 IU/L) or postmenopausal estradiol level (less than 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved; OR
- Underwent bilateral oophorectomy; OR
- Underwent hysterectomy; OR
- Underwent bilateral salpingectomy.
- 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 in Arizona
Scottsdale, Arizona, 85259
About this study
Official title: A Multidisciplinary Translational Approach to Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache
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.
The objective of the clinical trial component of the Focused Program is to determine whether intervention with erenumab is an effective treatment for PTH attributed to mTBI.
Read the detailed description
The human studies component of this Focused Program includes clinical phenotyping, neurophysiology, molecular and genetic biomarker discovery, brain imaging, and a clinical trial.These 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. These studies are described in more detail within a separate clinicaltrials.gov record.
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. Follow-up questionnaires, headache diary data, pain threshold results, and brain imaging data will be collected longitudinally during the clinical trial to assess for changes over time and associations of such changes with post-traumatic headache treatment outcomes. Due to slow enrollment, the study was later changed to open label since the estimated total enrollment would be inadequate for making comparisons between the placebo and erenumab groups.
- Conditions
- Post-Traumatic Headache
- Being tested
- Erenumab, Placebo
- Keywords
- headache, post-traumatic headache
- Medical subject headings
- Post-Traumatic Headache, Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErenumabDrug
Also called Aimovig
a CGRP receptor monoclonal antibody
PlaceboOther
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Erenumab | Experimental | 140 mg erenumab Receives: Drug: Erenumab |
| Placebo | Placebo comparator | placebo comparator Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Number of Days Experiencing Moderate-to-Severe Headaches
The number of days where subjects experienced moderate-to-severe headaches. This was measured at baseline, 9, 10, 11 and 12 weeks after administration of first dose of erenumab 140 mg or placebo. The change from baseline to week 12 is reported.
Measured: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
Secondary outcomes (4)
Responder Rate
The number of patients with at least a 50% reduction in days where they experienced a headache. This was measured at baseline, 9, 10, 11 and 12 weeks after administration of first dose of erenumab 140 mg or placebo. The change from baseline to week 12 is reported.
Measured: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
Chronic Headache
The number of patients with a chronic headache, defined as reporting a headache for at least 15 days. This was measured at baseline, 9, 10, 11 and 12 weeks after administration of first dose of erenumab 140 mg or placebo. The change from baseline to week 12 is reported.
Measured: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
Change in the Headache Impact Test (HIT-6)
The Headache Impact Test (HIT-6) measures the impact of headaches on a person's daily life. It assesses the frequency and severity of headaches, their functional limitations and the impact on daily activities such as work, education and social interactions. The HIT-6 test has 6 questions. Each of the six questions receives a score from 6-13. The final HIT-6 score can range from 36 to 78. A higher score indicates more disability due to headache. This was measured at baseline, 9, 10, 11 and 12 weeks after administration of first dose of erenumab 140 mg or placebo. The change from baseline to week 12 is reported.
Measured: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
Change in the Number of Days Where Acute Treatment Was Administered to Relieve a Headache
The change in the number of days where subjects underwent acute treatment to relieve a headache. Treatment days were days in which subjects took analgesic, triptan, or ergotamine containing medication, or they underwent device neuromodulation [e.g. vagal or trigeminal nerve electrical stimulation or single pulse transcranial magnetic stimulation]. This was measured at baseline,9, 10, 11 and 12 weeks after administration of first dose of erenumab 140mg or placebo. The change from baseline to 12 weeks is reported.
Measured: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2019
- Study start4 Jan 2021
- Primary completion10 Jan 2024
- Study completion10 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1 randomization to erenumab or placebo
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 6 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, Georgia Institute of Technology
- Responsible party
- Principal investigator, Todd J. Schwedt, Mayo Clinic
- Investigators
- Todd Schwedt, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04098250
- Sponsor's protocol ID
- 19-003200
- Status last verified
- Sep 2025
- First submitted
- 19 Sep 2019
- Last updated
- 23 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 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
- ClinicalTrials.gov ID
- NCT04098250
- Acronym / sponsor ID
- 19-003200
- Conditions
- Post-Traumatic Headache
- Keywords
- headache, post-traumatic headache
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 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, Georgia Institute of Technology
- Study start
- 4 Jan 2021 (actual)
- Primary completion
- 10 Jan 2024 (actual)
- Study completion
- 10 Jan 2024 (actual)
- First posted
- 23 Sep 2019 (actual)
- Results
- Posted 23 Oct 2025
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.
The objective of the clinical trial component of the Focused Program is to determine whether intervention with erenumab is an effective treatment for PTH attributed to mTBI.
Detailed description
The human studies component of this Focused Program includes clinical phenotyping, neurophysiology, molecular and genetic biomarker discovery, brain imaging, and a clinical trial.These 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. These studies are described in more detail within a separate clinicaltrials.gov record.
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. Follow-up questionnaires, headache diary data, pain threshold results, and brain imaging data will be collected longitudinally during the clinical trial to assess for changes over time and associations of such changes with post-traumatic headache treatment outcomes. Due to slow enrollment, the study was later changed to open label since the estimated total enrollment would be inadequate for making comparisons between the placebo and erenumab groups.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 1:1 randomization to erenumab or placebo
| Arm | Type | Receives |
|---|---|---|
| Erenumab | Experimental | Drug: Erenumab140 mg erenumab |
| Placebo | Placebo comparator | Other: Placeboplacebo comparator |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 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 be randomized to either of the two clinical trial treatment arms
- Willing to maintain a headache diary
Key exclusion criteria (40 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 an average of 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.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErenumabAlso: Aimoviga CGRP receptor monoclonal antibody | Drug | Erenumab |
| PlaceboPlacebo | Other | Placebo |
Primary outcome
Change in the Number of Days Experiencing Moderate-to-Severe Headaches
Time frame: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
The number of days where subjects experienced moderate-to-severe headaches. This was measured at baseline, 9, 10, 11 and 12 weeks after administration of first dose of erenumab 140 mg or placebo. The change from baseline to week 12 is reported.
4 secondary outcomes
Responder Rate
Time frame: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
Chronic Headache
Time frame: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
Change in the Headache Impact Test (HIT-6)
Time frame: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
Change in the Number of Days Where Acute Treatment Was Administered to Relieve a Headache
Time frame: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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?
A Phase 2 study testing Erenumab in people with 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 8 inclusion and 40 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 23 Oct 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 23 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in the Number of Days Experiencing Moderate-to-Severe Headaches (time frame: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported). 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 23 Oct 2025.