Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache

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 7-56 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.

Exclusion criteria

• 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.
• 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

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:

• 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