Clinical Characteristics and Pathophysiology of Post-Traumatic Headache
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Cortical Density
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Calcitonin Gene-Related Peptide (CGRP)
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
干预措施: Calcitonin Gene-Related Peptide (Drug)
Placebo
30 patients with PPTH wil be allocated to receive 40 mL Placebo (isotonic saline) over 20 minutes.
Other Name: Isotonic Saline
干预措施: Placebo (Drug)
结局指标
主要结局
Cortical Density
时间窗: 10 minutes
Cortical density will be assessed using Voxel-Based Morphometry.
Cognitive Function
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 10 minutes
Pressure Pain Threshold will be assessed using an Algometer.
Number and Location of Microhemorrhages
时间窗: 6 minutes
The number and location of microhemorrhages will be assessed using Susceptibility-Weighted Imaging.
Cerebral Blood Flow
时间窗: 7 minutes
Cerebral blood flow will be assessed using arterial spin labelling (ASL).
Brain Network Functional Connectivity
时间窗: 11 minutes
Brain network functional connectivity will be assessed using blood oxygen level-dependent functional magnetic resonance imaging.
Allodynia
时间窗: 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)
时间窗: 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
时间窗: 10 minutes
Cortical thickness will be assessed using Surface-Based Morphometry
Headache Area under the Curve
时间窗: 12 hours
Headache area under the curve is defined as headache intensity x duration up to 12 h after CGRP infusion
Depression
时间窗: 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
时间窗: 10 minutes
The white matter structural fiber integrity will be assessed using Diffusion Tensor Imaging
Number and Location of White Matter Lesions
时间窗: 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
时间窗: 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
时间窗: 12 hours
Time to maximum headache score on CGRP day compared to placebo day will be assessed using a headache questionnaire
次要结局
未报告次要终点
研究者
Henrik Schytz
Associate Professor of Neurology
Danish Headache Center