Clinical trial NCT03791515: Clinical Characteristics and Pathophysiology of Post-Traumatic Headache
Official title: Clinical Characteristics and Pathophysiology of Post-Traumatic Headache
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post-Traumatic Headache
Concussion, Mild
Lead sponsor: Danish Headache Center
Sponsor class: OTHER
First posted: 2019-01-02
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 100 patients with PPTH and 100 healthy controls will undergo a deep phenotyping of clinical characteristics and associated comorbidities. This is followed by a single MRI-session for all subjects.

Lastly, the 30 patients with PPTH will participate in a randomized, double-blind, placebo-controlled, 2-way crossover study. These patients will be allocated to receive intravenous infusion of CGRP or placebo (isotonic saline) over 20 minutes on 2 study days.
Primary purpose: OTHER

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Headache Characteristics
timeFrame: 50 minutes
measure: Headache Characteristics
timeFrame: 10 minutes
measure: Cognitive Function
timeFrame: 10 minutes
measure: Depression
timeFrame: 10 minutes
measure: Anxiety
timeFrame: 10 minutes
measure: Allodynia
timeFrame: 10 minutes
measure: Post-Traumatic Stress Disorder
timeFrame: 10 minutes
measure: Quality of Sleep: Pittsburgh Sleep Quality Index (PSQ-I)
timeFrame: 10 minutes
measure: Muscle Tenderness
timeFrame: 10 minutes
measure: Pressure Pain Threshold
timeFrame: 10 minutes
measure: Cortical Density
timeFrame: 10 minutes
measure: Cortical Thickness
timeFrame: 10 minutes
measure: Number and Location of Microhemorrhages
timeFrame: 6 minutes
measure: White Matter Structural Fiber Integrity
timeFrame: 10 minutes
measure: Number and Location of White Matter Lesions
timeFrame: 6 minutes
measure: Cerebral Blood Flow
timeFrame: 7 minutes
measure: Brain Network Functional Connectivity
timeFrame: 11 minutes
measure: Incidence of Headache Exacerbation with Migraine-Like Features
timeFrame: 60 minutes
measure: Headache Area under the Curve
timeFrame: 12 hours
measure: Time to Maximum Headache
timeFrame: 12 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Danish Headache Center
Study officials:
affiliation: Associate Professor
name: Henrik Schytz, MD
role: PRINCIPAL_INVESTIGATOR
References: