Clinical Characteristics and Pathophysiology of Post-Traumatic Headache
Condition: Post-Traumatic Headache; Concussion, Mild
MeSH terms: Post-Traumatic Headache; Brain Concussion; Headache
Study type: Interventional

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.
    

Intervention name(s): Calcitonin Gene-Related Peptide; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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 intervention name(s): CGRP; Isotonic Saline
Intervention MeSH terms: Calcitonin; Salmon calcitonin; Calcitonin Gene-Related Peptide; Katacalcin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
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.
Masking: None (Open Label)
Primary purpose: Other