Neurophysiological and Biomolecular Effects of Atogepant in High Frequency Episodic Migraine (ATOM Project)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Temporal summation threshold of the RIII reflex (continuos variable)
研究概览
简要总结
The investigators aim to assess and compare neurophysiological and biochemical changes induced by a 3-month treatment with atogepant (60 mg daily) in patients with high-frequency episodic migraine (8-14 monthly migraine days). Evaluations will include neurophysiological assessments (High-Density EEG, nociceptive reflexes, and visual evoked potentials) and biomolecular profiling (gene expression of endocannabinoid catabolizing enzymes, CGRP and PACAP plasma levels, and headache-specific microRNAs). Outputs will contribute to defining predictors of atogepant response, elucidating its effects on brain connectivity, excitability, and CGRP/endocannabinoid pathways, and identifying alternative therapeutic targets for non-responders.
详细描述
BACKGROUND:
Migraine is a highly prevalent neurological disease associated to a severe burden for patients and society. Despite recent advances, the knowledge of the molecular and biochemical pathways that turn on and off a migraine attack and lead to an increased frequency of attacks is still limited. In addition, the lack of predictors of the therapeutic response is a barrier to access to care and to a personalized approach. In recent years, several migraine-specific drugs have become available for the preventive treatment of the disease, which is aimed at reducing the frequency and the intensity of the attacks. Among the drugs currently available for migraine treatment, there are molecules that directly interfere with the calcitonin gene-related peptide (CGRP) pathway. Gepants, oral drugs that are CGRP receptor antagonists, represent a recently available pharmacological class for the acute and preventive treatment of migraines due to their specific mechanism of action.
The potential mechanism underlying the therapeutic benefit derived from drugs that block CGRP, as well as their impact on various biochemical and functional parameters associated with migraine pathophysiology, remains a topic of debate.
The objective of the ATOM project is to characterize the neurophysiological and biomolecular mechanisms underlying the therapeutic action of Atogepant (ATO), a drug belonging to the new pharmacological class of gepants. ATO has been shown to be effective in the preventive treatment of both chronic and episodic migraine. However, preventive treatment with gepants is still ineffective (reducing the number of monthly migraine days by less than 50%) in 30% of patients. This finding suggests that other biological pathways independent of CGRP may play a role in migraine pathophysiology. Among these, the endocannabinoid system has gained increasing importance over the years.
From a neurofunctional perspective, central sensitization is a significant aspect of migraine pathophysiology. Our group has demonstrated the utility of the nociceptive withdrawal reflex at the lower limb (RIII) in studying central sensitization. A subsequent study showed improvement in RIII reflex parameters in 30% of chronic migraine patients who responded to Erenumab after three months of treatment, suggesting a potential correlation between improved central sensitization and clinical benefit from anti-CGRP antibody treatment.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals aged between 18 and 70;
- •Diagnosis of episodic migraine according to ICHD-3 criteria;
- •Monthly migraine days between 8 and 14 (high-frequency episodic migraine pattern) in the 3 months before screening;
- •Individuals naïve to CGRP-targeted treatments;
- •No more than one ongoing migraine preventive treatment with a stable dose for at least 3 months.
排除标准
- •Contraindications to atogepant;
- •History of serious psychiatric conditions;
- •Diagnosis of other primary or secondary headaches (only sporadic tension-type headache is allowed);
- •Medical conditions considered clinically significant by the investigator;
- •Chronic pain conditions that need chronic treatment;
- •Abuse of alcohol and/or drugs;
- •Pregnancy or breastfeeding.
研究组 & 干预措施
HFEM group
High-frequency episodic migraine patients (8-14 migraine days per months) undergoing atogepant 60 mg daily for 3 months
干预措施: Atogepant 60 mg (Drug)
结局指标
主要结局
Temporal summation threshold of the RIII reflex (continuos variable)
时间窗: Baseline (T0) - three months of atogepant 60 mg treatment (T1)
Temporal summation threshold of the RIII reflex will be used to assess central sensitization after 3 months of treatment with atogepant 60 mg/day compared to baseline.
MAGL gene expression (continuos variable)
时间窗: Baseline (T0) - three months of atogepant 60 mg treatment (T1)
Changes in MAGL gene expression after 3 months of treatment with atogepant 60 mg/day
次要结局
- Habituation index of the nociceptive Blink Reflex (continuous variable)(Baseline (T0) - three months of atogepant 60 mg treatment (T1))
- Habituation of the visual evoked potential (continuous variable)(Baseline (T0) - three months of atogepant 60 mg treatment (T1))
- Functional brain connectivity (continuous variable)(Baseline (T0) - three months of atogepant 60 mg treatment (T1))
- Gene expression of miR-382-5p, miR-34a-5p, and miR-155 (continuous variables)(Baseline (T0) - three months of atogepant 60 mg treatment (T1))
- FAAH gene expression (continuous variable)(Baseline (T0) - three months of atogepant 60 mg treatment (T1))
- Plasma levels of CGRP (continuous variable)(Baseline (T0) - three months of atogepant 60 mg treatment (T1))
- Plasma levels of PACAP (continuous variable)(Baseline (T0) - three months of atogepant 60 mg treatment (T1))