Clinical Characteristics and Pathophysiology of Post-Traumatic Headache

Not Applicable

Completed

• Conditions: Concussion, Mild; Post-Traumatic Headache
• Interventions: Drug: Placebo; Drug: Calcitonin Gene-Related Peptide

• Registration Number: NCT03791515
• Lead Sponsor: Danish Headache Center

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.

Study Timeline

• Study Start: 2018-07-26
• Study First Submitted: 2018-07-27
• Status Verified: 2018-12
• Study First Submitted QC: 2018-12-29
• Study First Posted: 2019-01-02
• Primary Completion: 2019-12-01
• Study Completion: 2019-12-01
• Last Update Submitted: 2020-01-27
• Last Update Posted: 2020-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	30 patients with PPTH wil be allocated to receive 40 mL Placebo (isotonic saline) over 20 minutes. Other Name: Isotonic Saline
Calcitonin Gene-Related Peptide (CGRP)	Calcitonin Gene-Related Peptide	30 patients with PPTH will be allocated to receive intravenous infusion of 1.5 µg/min calcitonin-gene related peptide over 20 minutes Other Name: CGRP

Primary Outcome Measures

Name	Time	Method
Cortical Density	10 minutes	Cortical density will be assessed using Voxel-Based Morphometry.
Cognitive Function	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.
Headache Characteristics	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.
Anxiety	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).
Post-Traumatic Stress Disorder	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.
Muscle Tenderness	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.
Pressure Pain Threshold	10 minutes	Pressure Pain Threshold will be assessed using an Algometer.
Number and Location of Microhemorrhages	6 minutes	The number and location of microhemorrhages will be assessed using Susceptibility-Weighted Imaging.
Cerebral Blood Flow	7 minutes	Cerebral blood flow will be assessed using arterial spin labelling (ASL).
Brain Network Functional Connectivity	11 minutes	Brain network functional connectivity will be assessed using blood oxygen level-dependent functional magnetic resonance imaging.
Allodynia	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.
Quality of Sleep: Pittsburgh Sleep Quality Index (PSQ-I)	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.
Cortical Thickness	10 minutes	Cortical thickness will be assessed using Surface-Based Morphometry
Headache Area under the Curve	12 hours	Headache area under the curve is defined as headache intensity x duration up to 12 h after CGRP infusion
Depression	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).
White Matter Structural Fiber Integrity	10 minutes	The white matter structural fiber integrity will be assessed using Diffusion Tensor Imaging
Number and Location of White Matter Lesions	6 minutes	The number and location of white matter lesions will be assessed using T2-weighted Fluid-Attenuated Inversion Recovery.
Incidence of Headache Exacerbation with Migraine-Like Features	60 minutes	Migraine-like features are defined as headache fulfilling at least two of the following four characteristics: 1. Unilateral location; 2. Pulsating quality; 3. Moderate or severe pain intensity; 4. 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: 1. Nausea and/or vomiting; 2. Photophobia and phonophobia; 3. 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)
Time to Maximum Headache	12 hours	Time to maximum headache score on CGRP day compared to placebo day will be assessed using a headache questionnaire

Trial Locations

Locations (1)

Danish Headache Center; 🇩🇰 Glostrup, Denmark