Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache
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 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.
POST-TRAUMATIC HEADACHE ELIGIBILITY CRITERIA

 Inclusion Criteria:

 -  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 7-28 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.

 Exclusion Criteria:

 -  Episodic tension-type headache, migraine, or other headaches with at least 4 headache
 days/month on average over the 6 months prior to the mTBI resulting in PTH.

 -  Previous history of chronic headache (i.e. at least 15 headache days/month) 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.

 -  Current or prior use of preventive medications for migraine or other primary headache
 disorder.

 -  Use of onabotulinumtoxinA in the head, neck or face region within 12 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.

 -  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):

 1. Metal implants

 2. Aneurysm clips

 3. Severe claustrophobia

 4. Implanted electronic devices

 5. Insulin or infusion pump

 6. Cochlear/otologic/ear implant

 7. Non-removable prosthesis

 8. Implanted shunts/catheters

 9. Certain intrauterine devices

 10. Tattooed makeup

 11. Body piercings that cannot be removed

 12. Metal fragments

 13. 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):

 1. Dental braces or other non-removable devices (e.g., retainers)

 2. Prior brain surgery

 3. 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

 Inclusion Criteria:

 -  Adults 18-70 years of age.

 -  Willing and able to return for follow-up visits.

 Exclusion 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:

 1. Metal implants

 2. Aneurysm clips

 3. Severe claustrophobia

 4. Implanted electronic devices

 5. Insulin or infusion pump

 6. Cochlear/otologic/ear implant

 7. Non-removable prosthesis

 8. Implanted shunts/catheters

 9. Certain intrauterine devices

 10. Tattooed makeup

 11. Body piercings that cannot be removed

 12. Metal fragments

 13. Wire sutures or metal staples

 -  Factors that reduce MR image quality and interpretability:

 1. Dental braces or other non-removable devices (e.g., retainers)

 2. Prior brain surgery

 3. 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