Selective Activation of the Adrenomedullin Receptors in Migraine: A Randomized, Double-Blind, Placebo-Controlled Crossover Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 26
- 试验地点
- 2
- 主要终点
- Incidence of migraine attacks
研究概览
简要总结
Adrenomedullin is a neuropeptide implicated in the pathogenesis of migraine. This study investigates whether its administration, after pre-treatment with erenumab (a CGRP-receptor blocking monoclonal antibody), can trigger migraine attacks in individuals with migraine without aura.
详细描述
Adrenomedullin is an endogenous neuropeptide structurally related to CGRP that can activate both the adrenomedullin receptor and, to a lesser extent, the CGRP receptor. Prior human provocation studies have shown that administration of adrenomedullin can elicit migraine attacks in people with migraine. Because adrenomedullin lacks receptor selectivity, physiological responses observed after its administration might represent a composite of adrenomedullin-receptor activation and potential off-target activation of the CGRP receptor. The extent to which selective activation of the adrenomedullin receptor alone can provoke migraine-relevant responses remains unknown.
To isolate adrenomedullin receptor-mediated effects, participants will receive the monoclonal antibody erenumab prior to adrenomedullin administration in order to block CGRP receptor activation.
This study therefore aims to determine whether selective activation of adrenomedullin receptors - isolated from confounding CGRP receptor activation - can induce migraine-relevant physiological responses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Written informed consent has been obtained prior to the initiation of any study-specific procedures.
- •Age ≥18 years at the time of screening.
- •History of migraine without aura for at least 12 months prior to screening, with a frequency of 1-5 migraine attacks per month, based on medical records and/or patient self-report, and diagnosed in accordance with the ICHD-3 criteria.
排除标准
- •History of any other primary headache disorder, except for tension-type headache with <5 headache days per month, based on ICHD-3 classification.
- •History of any secondary headache disorder, per ICHD-3 criteria, prior to screening.
- •Use of prophylactic migraine medication within 30 days or within 5 plasma half-lives (whichever is longer) prior to screening.
- •Previous use of any therapies targeting the CGRP signaling pathway, including anti-CGRP ligand monoclonal antibodies, anti-CGRP receptor monoclonal antibodies, or small molecule CGRP receptor antagonists.
- •Known risk of self-harm or harm to others, including a history of suicidal behavior.
- •Any clinically significant disorder, condition, or disease (other than those permitted in the protocol) that, in the opinion of the investigator, could compromise participant safety or interfere with study procedures or data integrity.
- •Positive urine pregnancy test at screening or on Day 1 in female participants of childbearing potential.
- •Pregnancy or breastfeeding, or plans to become pregnant or breastfeed during the study period.
- •Evidence of current pregnancy or breastfeeding based on self-report or medical records.
- •Inability or unwillingness to complete all protocol-required visits and procedures, or concerns regarding protocol adherence, as judged by the investigator.
研究组 & 干预措施
Placebo
干预措施: Placebo (Other)
Adrenomedullin
干预措施: Adrenomedullin (Drug)
结局指标
主要结局
Incidence of migraine attacks
时间窗: Assessed from baseline to 12 hours post-infusion of adrenomedullin or placebo
Incidence of migraine attacks, defined by either: I. Headache fulfilling criteria C and D for migraine without aura according to ICHD-3 2 * Criterion C: At least two of the following: * Unilateral location * Pulsating quality * Moderate to severe pain intensity (≥4 on an 11-point numerical rating scale) * Aggravation by cough (in-hospital setting) or avoidance of routine physical activity (out-hospital setting) * Criterion D: At least one of the following: * Nausea and/or vomiting * Photophobia and phonophobia OR II. Headache that mimics the participant's usual spontaneous migraine attacks and is treated with acute migraine (rescue) medication.
次要结局
- Headache intensity(Assessed from baseline to 12 hours post-infusion of adrenomedullin or placebo)
研究者
Håkan Ashina
Associate Professor
Danish Headache Center