BIOmarkers of MIGraine: a Proof of Concept Study on the Stratification of Responders to CGRP Monoclonal Antibodies - Results from Magnetic Resonance Imaging
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 219
- 试验地点
- 4
- 主要终点
- resting state fMRI
研究概览
简要总结
The projects comprising in the multicenter BIOMIGA project have been preregistered earlier with ID NTC04503083 at clinicaltrials.gov. Here the imaging subproject within the overall BIOMIGA aims is specified. The hypotheses for this subproject of the magnetic resonance imaging part is based on hypotheses generating analyses of the data from one site (Hamburg, Germany) of this three-center study. At all three sites healthy controls and migraine patients underwent identical protocols with 3 types of magnetic resonance imaging including structural scans (MPRAGE), resting-state functional magnetic resonance imaging (rs-fMRI) as well as arterial spin labeling (ASL) with matched protocols across sites. Data was acquired before CGRP-antibody administration (day 1) and 12 weeks afterwards (day 2). We analyzed the data from one site (Hamburg, Germany) as hypotheses generating, published these data as a poster and aim to validate our results with the not-yet analyzed data from the two other sites (Pavia, Italy and Barcelona, Spain).
详细描述
The Hamburg data was processed as stated below and will be used as independent data set for hypotheses generation. The data of the two other sites (Italy and Spain) will be processed identically to the Hamburg data set:
rs-FMRI
Preprocessing of the resting-state functional MR data followed the SPM12 pipeline (https://www.fil.ion.ucl.ac.uk/spm/software/spm12/) using slice time correction, realignment, coregistration to the structural image, normalization into MNI space, and smoothing with an 8mm^3 Gausian kernel. Data was further analyzed using the CONN-toolbox (https://web.conn-toolbox.org/) where a 0.003-0.08 Hz temporal filter and denoising with linear regression of confounding effects (white matter, CSF, movement) and linear detrending. We choose:
- Local Homogeneity (LCOR),
- Global Correlations (GCOR),
- Seed-Based Correlations (SBC): Seed to voxel and ROI to ROI with an additional mask of the hypothalamus
- Independent Component Analyses (group-ICA),
- Amplitude of Low-Frequency Fluctuations (ALFF)
Statistical comparisons calculated are defined as primary and secondary outcomes below and include (i) prediction of treatment outcome (reduction in headache days) from T0 (further PR), (ii) alterations between T0 and T1, (iii) differences between healthy controls and migraine patients at T0 (further HvsPAT), and (iv) differences between responders and non-responder at T0 and T1.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 25 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Migraine patients
- •Adults between 25 and 55 years of age of both sexes;
- •Patients diagnosed with high-frequency migraine (HFM) 8 or more migraine days/month) or CM with or without aura (>15 headache days migraine/month, of which 8 have migraine characteristics) according to the International Classification of Headache Disorders, 3rd edition, (ICHD-3);
- •Females had to be postmenopausal for at least one year, surgically sterile or otherwise incapable of pregnancy, or using an acceptable method of birth control.
- •Healthy controls
- •Adults between 25 and 55 years of age of both sex;
- •Absence of any past, or first-degree familial history of recurrent primary or secondary headache disorders.
排除标准
- •For the clinical population:
- •Headache on more than 25 days/month in the last 3 months;
- •Medication overuse according to the ICHD-3 criteria.
- •For the entire study population (migraine and healthy controls)
- •Presence of any other significant medical condition (neurological disorders, severe psychiatric illness or cardiovascular disease);
- •Evidence of drug, smoking or alcohol abuse or dependence within 12 months prior to V1, based on medical records or patient self-report. An alcohol consumption >100g/week will be considered as an abuse;
- •Pregnant or breastfeeding women;
- •Women of childbearing potential, defined as all women physiologically capable of becoming pregnant who are not on contraception;
- •Concomitant use of other migraine preventive drugs that may interfere with the endpoints of the study.
结局指标
主要结局
resting state fMRI
时间窗: 1 year
Prediction of reduction in number of headache days at day 1. The statistical threshold will will be set to a small-volume corrected p\<0.05 in the combined data from Barcelona and Pavia.
Morphological MR
时间窗: 1 year
Prediction of reduction in number of headache days by gray and white matter density at day 1. The statistical threshold for the data of the two other sites will be set to voxel-wise FWE-corrected p\<0.05.
Arterial Spin Labelling MR
时间窗: 1 year
Prediction of reduction in number of headache days by brain perfusion at day 1. ASL was not yet analyzed for any of the sites. For the statistics we will use Cerebral Perfusion Images stemming from the toolbox ASLtbx (https://www.cfn.upenn.edu/zewang/ASLtbx\_manual.pdf). The statistical threshold will be set to voxel-wise FWE-corrected p\<0.05.
次要结局
- resting-state fMRI(1 year)
- Morphological MRI, resting-state fMRI and arterial spin labelling MRI(1 year)