Multidisciplinary Translational Approach to Investigate Mechanisms Predictors & Prevention of Persistent PTH
Multidisciplinary Translational Approach to Investigate Mechanisms Predictors & Prevention of Persistent PTH
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.
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.
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 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

 -  5 or more moderate or severe headache days during the 4-week run-in phase

 -  At least 80% compliant with diary keeping during the 4-week run-in phase (i.e.,
 provides data on at least 80% of days)

 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 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

 -  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):

 1. Metal implants

 2. Aneurysm clips

 3. Severe claustrophobia

 4. Implanted electronic device

 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 an exclusion for
 patients participating in the brain 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 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:

 1. At least 55 years of age with cessation of menses for 12 or more months; OR

 2. Younger than 55 years of age but no spontaneous menses for at least 2 years; OR

 3. 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

 4. Underwent bilateral oophorectomy; OR

 5. Underwent hysterectomy; OR

 6. 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