Unraveling the Spectrum of Migraine Resistant to Treatments: Searching for Novel Biological PHEnotypes and theRApeutic Approaches (SPHERA Project)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Gene expression of MAGL
研究概览
简要总结
Aim of the study was to assess a potential dysfunction of the endocannabidiome system (eCBome) in migraine patients. Migraine patients who will undergo preventive therapy with monoclonal antibodies directed against the calcitonin gene related peptide (mAbs) will be evaluated through a deep phenotyping of peripheral neurochemical biomarkers (eCBome, neuropeptides, cytokines and kynurenine levels, and microRNAs expression).
Primary aim is to assess baseline differences among those patients who achieved a reduction of monthly migraine days >/= 50% after three months of tretament (namely Responders) and those who did not (namely Non-responders).
详细描述
Previous evidence showed that endocannabidiome system (eCBome) is altered in migraine patients demonstrating: i) altered gene expression of catabolizing enzymes (MAGL and FAAH) in patients with episodic and chronic migraine compared to healthy controls; ii) altered peripheral levels of the endocannabinoid-like lipid palmitoylethanolamide (PEA) with evidence of increased PEA levels during the acute migraine phase.
Despite the high effectiveness and tolerability of mAbs monoclonal antibodies directed against the Calcitonin gene related peptide (mAbs), evidence from RCTs and real-life studies demonstrates that mAbs fail in 40% of patients. These patients may bear a non CGRP- dependent phenotype, potentially linked to eCBome dysfunction.
Primary aim is to perform a deep phenotyping of the whole cohort of migraine patients comparing the subgroups of those patients who will be Responders to mAbs treatment (namely those patients who achieved a reduction of monthly migraine days >/= 50%) compared to the Non-Respoder group (namely those patients who achieved a reduction of monthly migraine days < 50%) .
Neuropeptides, microRNAs, inflammatory cytokines, and kynurenine metabolites will be evaluated. These findings will allow the identification of a multibiomarkers panel signature of migraine patients resisting to specifically targeted preventive treatments and potentially unveiling other molecular targets.
STUDY DESIGN:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •male and female patients aged 18 to 75 years
- •diagnosis of episodic migraine or chronic migraine according to ICHD-3 criteria
- •for episodic migraine: 8-14 monthly migraine days in the previous 3 months
- •diagnosis of resistant migraine defined by: i) having failed at least 3 classes of migraine preventatives and ii) suffering from at least 8 debilitating monthly headache days for at least 3 consecutive months
- •patients naive to CGRP targeting treatments
排除标准
- •history of major psychiatric or other neurological conditions
- •diagnosis of other primary or secondary headache disorders (only sporadic tension-type headache is allowed if the patients can clearly differentiate between the 2 types of headaches)
- •changes in ongoing preventive treatment (if any) in the previous 3 months
- •clinically significant medical conditions
- •chronic pain conditions
- •alcohol and/or drug abuse
- •pregnancy or lactation
研究组 & 干预措施
Responders
Patients with high frequency episodic migraine (HFEM) or chronic migraine (CM) undergoing treatment with monoclonal antibodies directed against calcitonin gene related peptide pathway (mAbs) who obtained a reduction in monthly migraine days equal or higher than 50% after three months of treatment compared to pre-treatment values.
干预措施: MAbs (Drug)
Non-Responders
Patients with HFEM or CM undergoing mAbs treatment who obtained a reduction in monthly migraine days < 50% after three months of treatment compared to pre-treatment values.
干预措施: MAbs (Drug)
结局指标
主要结局
Gene expression of MAGL
时间窗: Baseline (T0) - three months of mAbs treatment (T1)
Gene expression of Monoacylglycerol lipase (MAGL) in peripheral blood mononuclear cells (PBMC) (continuous variable)
Gene expression of FAAH
时间窗: Baseline (T0) - three months of mAbs treatment (T1)
Baseline differences in gene expression of fatty acid amide hydrolase (FAAH) in peripheral blood mononuclear cells (PBMC) (continuous variable)
次要结局
- Plasma levels of AEA, 2-AG, PEA, OEA(Baseline (T0) - three months of mAbs treatment (T1))
- Plasma levels of CGRP, PACAP and VIP(Baseline (T0) - three months of mAbs treatment (T1))
- Gene expression of miR-382-5p, miR-34a, miR-30a and miR-155(Baseline (T0) - three months of mAbs treatment (T1))
- Shotgun analysis of microbiota(Baseline (T0) - three months of mAbs treatment (T1))
- Gene expression of catalyzing enzymes (DAGL, NAPE, NAAA)(Baseline (T0) - three months of mAbs treatment (T1))
- Plasma levels of IL-1beta, TNF-alpha, IL-4 and IL-10(Baseline (T0) - three months of mAbs treatment (T1))
- Plasma levels of kynurenic acid and quinolinic acid(Baseline (T0) - three months of mAbs treatment (T1))