Clinical Characteristics and Pathophysiology of Post-Traumatic Headache

Concussion, Mild Clinical Trial

Official title:

Clinical Characteristics and Pathophysiology of Post-Traumatic Headache

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03791515
• Other study ID #: H-18011477
• Status: Completed
• Phase: N/A
• Start date: July 26, 2018
• Est. completion date: December 1, 2019

Study information

• Verified date: December 2018
• Source: Danish Headache Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: December 1, 2019
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Concussion
• Concussion, Mild
• Headache
• Post-Traumatic Headache

Intervention

Drug:
• Calcitonin Gene-Related Peptide
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.
• Placebo
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.

Locations

Country	Name	City	State
Denmark	Danish Headache Center	Glostrup

Sponsors (1)

Lead Sponsor	Collaborator
Danish Headache Center

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Headache Characteristics	Headache characteristics will be assessed using a semi-structured interview.	50 minutes
Primary	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.	10 minutes
Primary	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.	10 minutes
Primary	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).	10 minutes
Primary	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).	10 minutes
Primary	Allodynia	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.	10 minutes
Primary	Post-Traumatic Stress Disorder	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.	10 minutes
Primary	Quality of Sleep: Pittsburgh Sleep Quality Index (PSQ-I)	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.	10 minutes
Primary	Muscle Tenderness	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 minutes
Primary	Pressure Pain Threshold	Pressure Pain Threshold will be assessed using an Algometer.	10 minutes
Primary	Cortical Density	Cortical density will be assessed using Voxel-Based Morphometry.	10 minutes
Primary	Cortical Thickness	Cortical thickness will be assessed using Surface-Based Morphometry	10 minutes
Primary	Number and Location of Microhemorrhages	The number and location of microhemorrhages will be assessed using Susceptibility-Weighted Imaging.	6 minutes
Primary	White Matter Structural Fiber Integrity	The white matter structural fiber integrity will be assessed using Diffusion Tensor Imaging	10 minutes
Primary	Number and Location of White Matter Lesions	The number and location of white matter lesions will be assessed using T2-weighted Fluid-Attenuated Inversion Recovery.	6 minutes
Primary	Cerebral Blood Flow	Cerebral blood flow will be assessed using arterial spin labelling (ASL).	7 minutes
Primary	Brain Network Functional Connectivity	Brain network functional connectivity will be assessed using blood oxygen level-dependent functional magnetic resonance imaging.	11 minutes
Primary	Incidence of Headache Exacerbation with Migraine-Like Features	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)	60 minutes
Primary	Headache Area under the Curve	Headache area under the curve is defined as headache intensity x duration up to 12 h after CGRP infusion	12 hours
Primary	Time to Maximum Headache	Time to maximum headache score on CGRP day compared to placebo day will be assessed using a headache questionnaire	12 hours