A Prospective Structural, Diffusion and Connectomics MRI Study on Migraine Patients Treated With Fremanezumab: The FreMRI Study
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 87
- 试验地点
- 1
- 主要终点
- Morphometric MRI parameters change from baseline during the 12-week period after the administration of Fremanezumab 1
研究概览
简要总结
The goal of this open-label, single-blind, controlled-trial is to evaluate brain changes evaluated with diffusion Magnetic Resonance Imaging (MRI) and functional MRI in patients with high-frequency episodic migraine and chronic migraine that will be treated with Fremanezumab, 12 weeks after the treatment onset, compared with the baseline.
Type of study: Phase IV clinical trial Participant population: high-frequency episodic migraine and chronic migraine. Participants will be treated with Fremanezumab.
详细描述
Fremanezumab is a monoclonal antibody targeting calcitonin C-reactive peptide (CGRP) that has proven to be effective in the treatment of episodic and chronic migraine. Due to the molecular weight of the drug, it is not supposed to cross the blood-brain barrier, acting peripherally.
Patients with migraine have shown gray and white matter changes that can be evaluated by magnetic resonance imaging (MRI).
In the present study, we aim to evaluate the presence of MRI changes in patients treated with Fremanezumab, 12 weeks after the treatment onset, compared with the baseline.
Number of Subjects: 87 patients. Study Duration per Subject Study duration per patient will be 8 months.
Study procedures:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Given that the efficacy of Fremanezumab has been established in the pivotal trials and due to sample-size reasons, we chose an open-label study. However, in order to avoid biases as much as possible, we will blind clinical data to the imaging analysts. Patients, clinicians involved in the Fremanezumab administration and data analysts cannot be blind to the information.
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
- 否
入选标准
- •Definite diagnosis of Migraine With Aura or Migraine Without Aura according to the International Classification of Headache Disorders, 3rd version (IHCD-3) (1).
- •Age between 18 and 65 years old.
- •Providing signed informed consent form.
- •Diagnosis of migraine before 50 years old.
- •History of migraine during at least 12 months prior to the study.
- •With eight or more migraine days per month within the last three months
排除标准
- •1.Presence of other primary headache disorders other than infrequent tension-type headache or medication overuse headache (MOH).
- •Participation of MOH patients will be restricted to a maximum of 50% of the total sample.
- •Prior use of Fremanezumab or another monoclonal antibody targeting CGRP or CGRP receptor.
- •Prior use of less than two or more than four preventive drugs according to the local national guidelines (34), with inadequate response after sufficient doses and enough time or lack of tolerability.
- •Any medical condition that might prevent study completion or interfere with interpretation of results.
- •History of any neurological or neurosurgical condition affecting the brain.
- •History of moderate-severe head trauma.
- •History of other chronic pain syndrome with a frequency of five or more days of pain per month.
- •Presence of daily headache
- •Pregnant or breastfeeding women.
- •Current or recent use of any other prophylactic treatment in the preceding five half-lives prior to the start.
- •Exposure to onabotulinumtoxinA in the preceding four months.
- •Any expected surgery during the study.
- •Use of opioids or barbiturates.
- •Any condition contraindicating an MRI acquisition.
- •Completing headache diary at least 80% of the time during the screening period
研究组 & 干预措施
Fremanezumab
Patients will be treated with 225 mg of subcutaneous injections of Fremanezumab per month.
Patients will do four monthly additional hospital visits. During each visit, occurrence of any adverse event will be interrogated; clinical situation will be analyzed and Fremanezumab will be administered. Visits will be performed at weeks 0, 4 and 8. Last visit will be performed after 12 weeks, without Fremanezumab injection.
干预措施: Fremanezumab Prefilled Syringe (Drug)
结局指标
主要结局
Morphometric MRI parameters change from baseline during the 12-week period after the administration of Fremanezumab 1
时间窗: Baseline, week 12-15
Cortical curvature
Morphometric MRI parameters change from baseline during the 12-week period after the administration of Fremanezumab 2.
时间窗: Baseline, week 12-15
Cortical thickness
Morphometric MRI parameters change from baseline during the 12-week period after the administration of Fremanezumab 3.
时间窗: Baseline, week 12-15
Gray matter volume
Diffusion MRI descriptors change from baseline during the 12-week period after the administration of Fremanezumab 1.
时间窗: Baseline, week 12-15
Fractional anisotropy
Diffusion MRI descriptors change from baseline during the 12-week period after the administration of Fremanezumab 3.
时间窗: Baseline, week 12-15
Radial diffusivity
Diffusion MRI descriptors change from baseline during the 12-week period after the administration of Fremanezumab 4.
时间窗: Baseline, week 12-15
Axial diffusivity
Morphometric MRI parameters change from baseline during the 12-week period after the administration of Fremanezumab 4.
时间窗: Baseline, week 12-15
Surface area,
Diffusion MRI descriptors change from baseline during the 12-week period after the administration of Fremanezumab 2.
时间窗: Baseline, week 12-15
Mean diffusivity
Structural connectivity change from baseline during the 12-week period after the administration of Fremanezumab 1.
时间窗: Baseline, week 12-15
Number of streamlines in the connection between two regions
Structural connectivity change from baseline during the 12-week period after the administration of Fremanezumab 2.
时间窗: Baseline, week 12-15
Mean fractional anisotropy in the connection between two regions
Structural connectivity change from baseline during the 12-week period after the administration of Fremanezumab 3.
时间窗: Baseline, week 12-15
Mean axial diffusivity in the connection between two regions
Resting-state functional connectivity change from baseline during the 12-week period after the administration of Fremanezumab.
时间窗: Baseline, week 12-15
Z-score
次要结局
- Relationship between morphometric MRI parameters and the change in monthly migraine days 1.(Baseline, week 12-15)
- Relationship between morphometric MRI parameters and the change in monthly migraine days 2.(Baseline, week 12-15)
- Relationship between morphometric MRI parameters and the change in monthly migraine days 3.(Baseline, week 12-15)
- Relationship between morphometric MRI parameters and the change in monthly migraine days 4.(Baseline, week 12-15)
- Relationship between diffusion descriptors and the change in monthly migraine days 1.(Baseline, week 12-15)
- Relationship between diffusion descriptors and the change in monthly migraine days 2.(Baseline, week 12-15)
- Relationship between diffusion descriptors and the change in monthly migraine days 3.(Baseline, week 12-15)
- Relationship between diffusion descriptors and the change in monthly migraine days 4.(Baseline, week 12-15)
- Relationship between structural connectivity and the change in monthly migraine days 1. [Time Frame: baseline, week 12](Baseline, week 12-15)
- Relationship between structural connectivity and the change in monthly migraine days 2. [Time Frame: baseline, week 12](Baseline, week 12-15)
- Relationship between structural connectivity and the change in monthly migraine days 3. [Time Frame: baseline, week 12](Baseline, week 12-15)
- Relationship between resting-state functional connectivity and the change in monthly migraine days. [Time Frame: baseline, week 12](Baseline, week 12-15)
- Baseline morphometric MRI parameters will be assessed as potential predictors of change in monthly migraine days 1.(Baseline)
- Baseline morphometric MRI parameters will be assessed as potential predictors of change in monthly migraine days 2.(Baseline)
- Baseline morphometric MRI parameters will be assessed as potential predictors of change in monthly migraine days 3.(Baseline)
- Baseline morphometric MRI parameters will be assessed as potential predictors of change in monthly migraine days 4.(Baseline)
- Baseline diffusion MRI descriptors will be assessed as potential predictors of change in monthly migraine headache days 1.(Baseline)
- Baseline diffusion MRI descriptors will be assessed as potential predictors of change in monthly migraine headache days 2.(Baseline)
- Baseline diffusion MRI descriptors will be assessed as potential predictors of change in monthly migraine headache days 3.(Baseline)
- Baseline diffusion MRI descriptors will be assessed as potential predictors of change in monthly migraine headache days 4.(Baseline)
- Baseline structural connectivity will be assessed as potential predictors of change in monthly migraine days.(Baseline)
- Baseline resting-state functional connectivity will be assessed as potential predictors of change in monthly migraine days(Baseline)
研究者
David García Azorín
Headache Unit, Department of Neurology, Principal Investigator
Hospital Clínico Universitario de Valladolid