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

January 17, 2024 updated by: Todd J. Schwedt, Mayo Clinic

A Multidisciplinary Translational Approach to Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache - Human Studies Protocol: Individual Projects Excluding Clinical Trial

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

Study Overview

Status

Recruiting

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.

Study Type

Observational

Enrollment (Estimated)

264

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic
        • Principal Investigator:
          • Todd Schwedt, MD
        • Contact:
      • Phoenix, Arizona, United States, 85012
        • Recruiting
        • Phoenix VA Health Care System
        • Contact:
      • Scottsdale, Arizona, United States, 85259
        • Recruiting
        • Mayo Clinic
        • Principal Investigator:
          • Todd Schwedt, MD
        • Contact:
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Not yet recruiting
        • Mayo Clinic
        • Contact:
        • Principal Investigator:
          • Kevin Barrett, MD
    • Minnesota
      • Rochester, Minnesota, United States, 55901
        • Recruiting
        • Mayo Clinic
        • Principal Investigator:
          • Dmitry Esterov, DO
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Post-Traumatic Headache
Individuals who have post-traumatic headache attributed to mild traumatic brain injury according to ICHD-3 diagnostic criteria
Healthy Control
Healthy controls will have no history of traumatic brain injury and no history of migraine or other headaches

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Longitudinal Assessment of PTH Phenotype
Time Frame: baseline with longitudinal follow-up at weeks four and sixteen
descriptive analysis of post-traumatic headache characteristics such as headache frequency and severity, and characteristics of associated conditions such as symptoms of sensory hypersensitivities, anxiety, depression, insomnia, autonomic dysfunction, and cognitive function
baseline with longitudinal follow-up at weeks four and sixteen
Longitudinal Assessment of Cutaneous Pain Thresholds
Time Frame: baseline with longitudinal follow-up at weeks four and sixteen
heat pain thresholds on the skin determined by quantitative sensory testing
baseline with longitudinal follow-up at weeks four and sixteen
Longitudinal Assessment of Visual Pain Thresholds from Bright Light Exposure
Time Frame: baseline with longitudinal follow-up at weeks four and sixteen
visual pain thresholds to different light intensities
baseline with longitudinal follow-up at weeks four and sixteen
Longitudinal Assessment of Brain MRI
Time Frame: baseline with longitudinal follow-up at weeks four and sixteen
structural brain imaging to include measures such as cortical thickness, regional volumes, brain curvature, white matter tract integrity, and functional brain imaging measures such as resting state functional connectivity and pain-induced brain activation
baseline with longitudinal follow-up at weeks four and sixteen
Longitudinal Assessment of Blood Based Biomarkers
Time Frame: baseline with longitudinal follow-up at weeks four and sixteen
blood-based biomarkers, including DNA and targeted serum proteins, associated with acute and persistent post-traumatic headache and response to therapy
baseline with longitudinal follow-up at weeks four and sixteen
Longitudinal Assessment of Post-traumatic Headache Biomarkers
Time Frame: baseline with longitudinal follow-up at weeks four and sixteen
clinical characteristics, pain thresholds, and brain imaging features as described above that are associated with acute post-traumatic headache and persistent post-traumatic headache; that predict the persistent of post-traumatic headache; and that predict and measure treatment response
baseline with longitudinal follow-up at weeks four and sixteen

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 9, 2020

Primary Completion (Estimated)

August 1, 2024

Study Completion (Estimated)

August 1, 2024

Study Registration Dates

First Submitted

April 25, 2020

First Submitted That Met QC Criteria

April 29, 2020

First Posted (Actual)

April 30, 2020

Study Record Updates

Last Update Posted (Estimated)

January 18, 2024

Last Update Submitted That Met QC Criteria

January 17, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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