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

POST-TRAUMATIC HEADACHE ELIGIBILITY CRITERIA

Inclusion Criteria:

• Have a diagnosis of acute PTH attributed to mild traumatic injury to the head asdefined 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 wouldinterfere with the person's ability to provide informed consent and complete studyprocedures.

• Started or changed dose of a headache preventive medication within the 3 monthsprior to screening.

• Use of onabotulinumtoxinA in the head, neck or face region within 6 months ofscreening.

• During the 6 months before screening, use of opioids or barbiturates on at least 4days per month.

• Subjects who underwent an intervention or used a device (e.g., nerve blocks,transcranial magnetic stimulation, vagal nerve stimulation, or electrical trigeminalnerve 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 orinterfere 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 (onlyfor 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 thoseindividuals 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 willsignificantly impact MRI data.

• Sensory disorders that in the investigator's opinion might affect perception ofcutaneous thermal stimuli (e.g., peripheral neuropathy) (only for those individualsundergoing pain threshold testing).

• Pregnancy

• Breastfeeding

• Currently or within 90 days prior to screening: received treatment in another drugstudy 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 3days per month is allowed).

• Diminished decision-making capacity that in the investigator's opinion wouldinterfere with the person's ability to provide informed consent and complete studyprocedures.

• During the 6 months before screening, use of opioids or barbiturates on an averageof 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 orinterfere 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 willsignificantly impact MRI data.

• Sensory disorders that in the investigator's opinion might affect perception ofcutaneous thermal stimuli (e.g., peripheral neuropathy).

• Pregnancy

• Breastfeeding

• Currently or within 90 days prior to screening: received treatment in another drugstudy or an investigational device study

• Has previously received any CGRP ligand or receptor targeted monoclonal antibody