Clinical trial NCT04369729: Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache
Official title: A Multidisciplinary Translational Approach to Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache - Human Studies Protocol: Individual Projects Excluding Clinical Trial
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Post-Traumatic Headache
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: University of Arizona
name: Translational Genomics Research Institute
name: Arizona State University
name: Phoenix VA Health Care System
name: United States Department of Defense
name: Amgen
First posted: 2020-04-30
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study participants will be enrolled from the Mayo Clinic and Phoenix VA Healthcare System and from the surrounding region

Brief 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

Detailed description: 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.

Eligibility criteria: 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):

  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

Primary outcomes:
measure: Longitudinal Assessment of PTH Phenotype
timeFrame: baseline with longitudinal follow-up at weeks four and sixteen
measure: Longitudinal Assessment of Cutaneous Pain Thresholds
timeFrame: baseline with longitudinal follow-up at weeks four and sixteen
measure: Longitudinal Assessment of Visual Pain Thresholds from Bright Light Exposure
timeFrame: baseline with longitudinal follow-up at weeks four and sixteen
measure: Longitudinal Assessment of Brain MRI
timeFrame: baseline with longitudinal follow-up at weeks four and sixteen
measure: Longitudinal Assessment of Blood Based Biomarkers
timeFrame: baseline with longitudinal follow-up at weeks four and sixteen
measure: Longitudinal Assessment of Post-traumatic Headache Biomarkers
timeFrame: baseline with longitudinal follow-up at weeks four and sixteen
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix VA Health Care System
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Todd Schwedt
role: PRINCIPAL_INVESTIGATOR
References: