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

NCT04369729 | Completed DMC

• 1 other identifier: 20-003732
• Study Type: observational
• Target: 101
• Locations: 1 country
• Sites: 5

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

Conditions

Post-Traumatic Headache

Outcome Measures

Primary Outcomes (6)

• Longitudinal Assessment of PTH Phenotype

  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

  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

  visual pain thresholds to different light intensities

  baseline with longitudinal follow-up at weeks four and sixteen

• Longitudinal Assessment of Brain MRI

  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

  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

  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

Study Arms (2)

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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• University of Arizona: collaborator
• Translational Genomics Research Institute: collaborator
• Arizona State University: collaborator
• Phoenix VA Health Care System: collaborator
• United States Department of Defense: collaborator
• Amgen: collaborator

Study Sites (5)

Phoenix VA Health Care System

Phoenix, Arizona, 85012, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic

Rochester, Minnesota, 55901, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Post-Traumatic Headache

Condition Hierarchy (Ancestors)

Headache Disorders, Secondary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Todd Schwedt

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 25, 2020
• First Posted: April 30, 2020
• Study Start: September 9, 2020
• Primary Completion: August 31, 2025
• Study Completion: August 31, 2025
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)