Clinical Characteristics and Pathophysiology of Post-Traumatic Headache

Danish Headache Center200 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

NONE

Enrollment

200

Conditions

Post-Traumatic Headache Concussion, Mild

Interventions

Calcitonin Gene-Related PeptideDRUG

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.

PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Danish Headache Center

Glostrup Municipality, Denmark

Outcomes

Primary Outcomes

Headache Characteristics

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

Time frame: 50 minutes

Headache Characteristics

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.

Time frame: 10 minutes

Cognitive Function

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.

Time frame: 10 minutes

Depression

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).

Time frame: 10 minutes

Anxiety

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).

Time frame: 10 minutes

Allodynia

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.