Skip to main content
OpenTrials
Completed

NCT Number: NCT03791515

Clinical Characteristics and Pathophysiology of Post-Traumatic Headache

To better understand the clinical characteristics and complex pathophysiological events that constitute persistent post-traumatic headache (PPTH) and to identify possible calcitonin gene-related peptide (CGRP) hypersensitivity in PPTH patients.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Post-Traumatic Headache Brain Concussion Brain Diseases Brain Injuries Brain Injuries, Traumatic Central Nervous System Diseases Concussion, Mild Craniocerebral Trauma Head Injuries, Closed Headache Disorders Headache Disorders, Secondary Nervous System Diseases Trauma, Nervous System Wounds and Injuries Wounds, Nonpenetrating

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Danish Headache Center

Glostrup Municipality, 2600, Denmark

About this study

The present project will embark upon identifying novel PTH-specific biomarkers by incorporating a plethora of scientific approaches. First, clinical biomarkers will be assessed by deep phenotyping of clinical characteristics and associated comorbidities using a semi-structured interview and multiple validated questionnaires. Second, biochemical biomarkers will be determined by plasma levels measurements of blood markers for headache hypersensitivity and neuronal/axonal damage. Third, imaging biomarkers will be established by magnetic resonance imaging (MRI) to assess structural and functional changes in the brain. Lastly, molecular biomarkers will be identified by examining whether intravenous infusion of calcitonin gene-related peptide (CGRP) provokes headache attacks mimicking the usual headache phenotype in subjects with PTH. This would determine whether PTH patients exhibit hypersensitivity to CGRP (molecular biomarker) and advance our understanding of the complex pathophysiological events that constitute the headache phenotypes in PTH sufferers.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for PPTH patients:

  • 18-65 years of age
  • Subject has PPTH in accordance with the diagnostic criteria of the International Headache Society (IHS)
  • Concussion (mild traumatic brain injury) occured > 12 months ago
  • Subject, who are fertile women, must be on safe contraceptives

Exclusion criteria

for PPTH patients:

  • Pre-trauma existing primary headache disorder (maximum 1 day/per month with tension-type headache) and medication-overuse headache
  • > 1 episode with a sustained concussion
  • Whiplash
  • Pregnant or lactating women
  • Cardiovascular disease of any kind
  • Hypertension on the experimental day
  • Hypotension on the experimental day
  • Pre-trauma existing psychiatric disorder of any kind - unless well-regulated
  • Any anamnestic or clinical signs of any kind deemed relevant for the study by the physician examining the subject
  • Any MRI contraindication and a wish of not being informed about unexpected MRI changes

Treatment and study plan

Calcitonin Gene-Related Peptide

Drug

A randomized clinical trial with a double-blinded, randomized, placebo-controlled crossover design. 30 PPTH patients will be included. All participants will receive continuous intravenous infusion of 1.5 µg/min CGRP over 20 min.

The following variables will be recorded before, during and after infusion (every 10 min over 60 min): headache intensity on a verbal rating scale from 0 to 10 and headache characteristics. At 90 min, participants will be discharged and instructed to fill out a headache diary for 24 hours from start of infusion.

Other names: CGRP

Placebo

Drug

A randomized clinical trial with a double-blinded, randomized, placebo-controlled crossover design. 30 PPTH patients will be included. All participants will receive continuous intravenous infusion of 40 mL placebo (isotonic saline) over 20 min.

The following variables will be recorded before, during and after infusion (every 10 min over 60 min): headache intensity on a verbal rating scale from 0 to 10 and headache characteristics. At 90 min, participants will be discharged and instructed to fill out a headache diary for 24 hours from start of infusion.

Other names: Isotonic Saline

Primary outcomes

  1. Headache Characteristics

    Time frame: 50 minutes

    Headache characteristics will be assessed using a semi-structured interview.

  2. Headache Characteristics

    Time frame: 10 minutes

    Headache characteristics will be assessed using Headache Under-Response to Treatment Index (HURT-Index) questionnaire. The total score ranges from 0 to 24 with a higher score indicating a lower effectiveness of intervention against headache.

  3. Cognitive Function

    Time frame: 10 minutes

    Cognitive function will be assessed using Montreal Cognitive Assessment (MoCA) questionnaire. The total score ranges from 0 to 30 points. The MoCA is divided into 7 subscores: visuospatial/executive (5 points); naming (3 points); memory (5 points for delayed recall); attention (6 points); language (3 points); abstraction (2 points); and orientation (6 points). One point is added if the subject has ≤12 years of education. A total of 30 points may be given. A score ≤25 indicates some degree of cognitive impairment.

  4. Depression

    Time frame: 10 minutes

    Depression will be assessed using Hospital Anxiety and Depression Scale (HADS) questionnaire. The total score ranges from 0-21.

    A score of 0-7 points is regarded as being in the normal range. A score of 8-10 points is suggestive of a depressive state (borderline abnormal).

    A score of 11-21 points indicates a probable presence of a depressive state (abnormal).

  5. Anxiety

    Time frame: 10 minutes

    Anxiety will be assessed using Hospital Anxiety and Depression Scale (HADS) questionnaire.

    The total score ranges from 0-21. A score of 0-7 points is regarded as being in the normal range. A score of 8-10 points is suggestive of a state of anxiety (borderline abnormal).

    A score of 11-21 points indicates a probable presence of an anxiety disorder (abnormal).

  6. Allodynia

    Time frame: 10 minutes

    Allodynia will be assessed using Allodynia Symptom Checklist (ASC-12) questionnaire. The total score ranges from 0-24 points.

    A score of 0-2 suggests no allodynia. A score of 3-5 suggests mild allodynia. A score of 6-8 suggests moderate allodynia. A score of 9 or more suggests severe allodynia.

  7. Post-Traumatic Stress Disorder

    Time frame: 10 minutes

    Post-traumatic stress disorder will be assessed using Harvard Trauma Questionnaire (HTQ). The total score ranges from 16-64. The total score is divided with 16 and a clinical cut-off score of 2.5 is set to be indicative of PTSD.

  8. Quality of Sleep: Pittsburgh Sleep Quality Index (PSQ-I)

    Time frame: 10 minutes

    Quality of Sleep will be assessed using Pittsburgh Sleep Quality Index (PSQ-I). The measure consists of 19 individual items, creating 7 components that produce one global score. The total PSQ-I score ranges from 0 to 21 with lower scores indicating a healthier sleep quality.

  9. Muscle Tenderness

    Time frame: 10 minutes

    Muscle tenderness will be assessed using Total Tenderness Score (TTS). The total score ranges from 0-48 with higher scores indicating a higher degree of muscle tenderness.

  10. Pressure Pain Threshold

    Time frame: 10 minutes

    Pressure Pain Threshold will be assessed using an Algometer.

  11. Cortical Density

    Time frame: 10 minutes

    Cortical density will be assessed using Voxel-Based Morphometry.

  12. Cortical Thickness

    Time frame: 10 minutes

    Cortical thickness will be assessed using Surface-Based Morphometry

  13. Number and Location of Microhemorrhages

    Time frame: 6 minutes

    The number and location of microhemorrhages will be assessed using Susceptibility-Weighted Imaging.

  14. White Matter Structural Fiber Integrity

    Time frame: 10 minutes

    The white matter structural fiber integrity will be assessed using Diffusion Tensor Imaging

  15. Number and Location of White Matter Lesions

    Time frame: 6 minutes

    The number and location of white matter lesions will be assessed using T2-weighted Fluid-Attenuated Inversion Recovery.

  16. Cerebral Blood Flow

    Time frame: 7 minutes

    Cerebral blood flow will be assessed using arterial spin labelling (ASL).

  17. Brain Network Functional Connectivity

    Time frame: 11 minutes

    Brain network functional connectivity will be assessed using blood oxygen level-dependent functional magnetic resonance imaging.

  18. Incidence of Headache Exacerbation with Migraine-Like Features

    Time frame: 60 minutes

    Migraine-like features are defined as headache fulfilling at least two of the following four characteristics:

    • Unilateral location
    • Pulsating quality
    • Moderate or severe pain intensity
    • Aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs)

    And during headache at least one of the following must be fulfilled:

    • Nausea and/or vomiting
    • Photophobia and phonophobia
    • Headache mimicking the usual exacerbated headache with migraine-like features

    If the participant fulfills these criteria at baseline, then incidence of exacerbated headache with migraine-like features is defined as:

    • An increase in headache intensity combined with an increase in the degree nausea and/or photophobia and phonophobia (based on a mild / moderate / severe scale)

  19. Headache Area under the Curve

    Time frame: 12 hours

    Headache area under the curve is defined as headache intensity x duration up to 12 h after CGRP infusion

  20. Time to Maximum Headache

    Time frame: 12 hours

    Time to maximum headache score on CGRP day compared to placebo day will be assessed using a headache questionnaire

Sponsors and collaborators

Lead sponsor

Danish Headache Center

Other

Registry information

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Jan 2, 2019
Registry last updated
Jan 29, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.