Neurophysiological, Biomolecular and Psychological Aspects of Erenumab Treatment in Chronic Migraine: an Open Label, Hypothesis Generator Study
试验速览
- 阶段
- 不适用
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Spinal sensitization
研究概览
简要总结
Monoclonal antibodies (mABs) targeting calcitonin gene-related peptide (CGRP) proved effective in the preventive treatment of episodic and chronic migraine as well as in difficult-to-treat patients such as those who had previously failed multiple prevention treatments or those with associated medication overuse (MO).
A characteristic dysfunction in Chronic Migraine (CM) is sensitization, occurring peripherally in the trigeminovascular system but then spreading to the central nervous system, where it manifests with an increased neuronal excitability in multiple areas. Several neurophysiological studies in CM patients have demonstrated the occurrence of central sensitization in the brain as well as at the spinal level.
MicroRNAs (miRNAs) are involved in the generation and maintenance of chronic pain. Current evidence suggests that specific miRNAs may also play a role in migraine, thus representing possible biomarkers of the disease. A previous study reported an upregulation of miR-34a-5p and miR-382-5p, implicated in the regulation of GABAergic signaling and IL-10 gene expression respectively, during migraine attacks.
The aim of this open label, hypothesis generating study is the evaluation of the impact of erenumab treatment on neurophysiological, biomolecular and psychological aspects in a representative cohort of CM patients who had previously failed at least 2 preventive treatments.
详细描述
This study consisted of a first screening visit with a Neurologist of the Headache Science Centre of the IRCCS Mondino Foundation, during which a full neurological and general examination was performed, and the data collected on the routine headache diary used by all patients attending Mondino Foundation was checked to confirm inclusion/exclusion criteria.
If a patient fulfilled criteria, he/she was enrolled in a baseline observation period for a month. At the end of the baseline observation period (T0), if inclusion/exclusion criteria were still satisfied, patients completed the following procedures: recording of clinical and demographical features, vital signs evaluation, neurophysiological assessment and psycological interview based on DSM (The Diagnostic and Statical Manual of Mental Disorders), venous blood sampling, and compilation of a set of self-administered questionnaires about psychological state, health status and quality of life.
At T0, the patients were treated with the first dose of erenumab 70 mg subcutaneously.
After 28 days (4 full weeks), patients returned for the second visit (T1) to report clinical variables and adverse events. During T1, the second injection of erenumab 70 mg was administered, while a third and last dose of erenumab 70 mg was self-administered at home by the patients themselves after an additional 28-day interval (T2). The last visit of the study (T3) was then planned 56 days from T1, that was 28 days after the last dose of erenumab. At T3, the patients were tested with the same multi-disciplinary evaluation performed at T0: recording of clinical and demographical features, vital signs evaluation, neurophysiological assessment, venous blood sampling, and compilation of questionnaires concerning patients' psychological state, health status and quality of life.
Nociceptive withdrawal reflex measurements. The nociceptive withdrawal reflex (NWR) is considered an objective and solid neurophysiological technique for the study of spinal nociceptive transmission. The reflex was recorded in the lower limb according to a well validated procedure, in a quiet environment by an expert technician between 09:00 AM and 11:00 AM. Patients were in a comfortable position with their ankle flexed at 90° and knee flexed at 130°. The sural nerve was stimulated electrically behind the lateral malleolus with a pair of Ag/AgCl surface electrodes. The electrical stimulation was made of 5 consecutive squared pulses (1 ms, 200 Hz), randomly delivered every 60-120 seconds. The electromyographic sweep (Synergy, Medelec, United Kingdom) was recorded from the capitis brevis of the homolateral biceps femoris with a pair of Ag/AgCl surface electrodes. A staircase method was used for all the threshold evaluations, and the intensity was increased by 0.3 mA per step. The recording parameters were: analysis time 300 ms, sensitivity 20 mV, and filter bandpass 3 to 3000 Hz.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
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
- •age 18 to 65 years
- •history of CM or CM+MO for at least 12 months prior to enrollment [10]
- •previous failure of at least two different pharmacological classes of preventive therapies
排除标准
- •other neurologic or neuropsychiatric diseases
- •other chronic painful syndromes
- •other types of primary or secondary headaches
- •use of more than one preventive medication at baseline
- •previous reported adverse reaction to latex
- •pregnancy or lactation
研究组 & 干预措施
Chronic migraine patients
Three monthly administration of erenumab 70 mg subcutaneously.
干预措施: Erenumab (Drug)
结局指标
主要结局
Spinal sensitization
时间窗: Change in TST (mA) at T3 (12 weeks later) when compared to baseline (T0)
Measured by the temporal summation threshold (TST) of the nociceptive withdrawal reflex
次要结局
- Inflammatory biomarker profile(Change in miR-382-5p at T3 (12 weeks later) when compared to baseline (T0))
- Migraine Disability Assessment (MIDAS)(Change in MIDAS score at T3 (12 weeks later) when compared to baseline (T0))
- Spinal sensitization(Change in RTh (mA) at T3 (12 weeks later) when compared to baseline (T0))
- inflammatory biomarker profile(Change in miR-34a-5p at T3 (12 weeks later) when compared to baseline (T0))
- Migraine-Specific Quality-of-Life Questionnaire (MSQ)(Change in MSQ2 score at T3 (12 weeks later) when compared to baseline (T0))
- Toronto Alexithymia Scale (TAS-20)(Change in TAS-20 score at T3 (12 weeks later) when compared to baseline (T0))
- Percentage of patients with positive clinical outcome(Percentage of 50% Responder patients at T3 (12 weeks after T0))
- Headache Impact Test-6 (HIT-6)(Change in HIT-6 score at T3 (12 weeks later) when compared to baseline (T0))
- Allodynia Symptom Checklist (ASC-12)(Change in ASC-12 score at T3 (12 weeks later) when compared to baseline (T0))
- Short Form Health Survey (SF-36)(Change in SF-36 score at T3 (12 weeks later) when compared to baseline (T0))
- Hospital Anxiety and Depression Scale (HADS)(Change in HADS score at T3 (12 weeks later) when compared to baseline (T0))
- Leeds Dependence Questionnaire (LDQ)(Change in LDQ score at T3 (12 weeks later) when compared to baseline (T0))