Induction of Migraine Attacks With Aura Using Pituitary Adenylate Cyclase Activating Polypeptide-38: A Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 21
- 主要终点
- Incidence of migraine attacks with aura
研究概览
简要总结
Pituitary Adenylate Cyclase Activating Polypeptide-38 (PACAP-38) is a key neuropeptide in migraine pathophysiology and treatment. This study investigates whether PACAP-38 administration can trigger aura in individuals with a diagnosis of migraine with aura.
详细描述
In a series of studies, pharmacological triggers of migraine headache were able to induce aura as well migraine headache. Recent open-label findings show that calcitonin gene-related peptide (CGRP) can trigger aura attacks-despite its limited ability to cross the blood-brain barrier. This suggests CGRP might induce migraine aura via trigeminovascular activation, the same pathway involved in migraine headache. To further explore this concept, it is fundamental to examine whether other migraine-inducing signaling molecules that pass the BBB to a minimal degree, such as PACAP-38, are able to induce aura as well. If PACAP-38 is able to induce aura, the anti-PACAP monoclonal antibody may provide a promising therapeutic option for preventing migraine with aura.
To validate this effect, a randomized, double-blind, placebo-controlled trial is essential. Its outcomes could inform future therapies targeting the migraine-aura connection.
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
- •Age 18 to 65 years of age upon entry into screening
- •History of migraine with aura for ≥ 12 months according to the International Classification of Headache Disorders 3rd Edition (ICHD-3) criteria
- •≥ 1 monthly day with aura that meets criteria as aura on average across the three months before screening
- •Provision of informed consent prior to initiation of any study-specific activities/procedures.
排除标准
- •Any history of a primary or secondary headache disorder other than migraine without aura, migraine with aura, chronic migraine, and episodic tension-type headache
- •History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion
- •The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior
- •Female subjects of childbearing potential with a positive pregnancy test during any study visit
- •Cardiovascular disease of any kind, including cerebrovascular diseases Hypertension (systolic blood pressure of ≥150 mmHg and/or diastolic blood pressure of ≥100 mmHg) prior to the start of infusion on the experimental day Hypotension (systolic blood pressure of ≤90 mmHg and/or diastolic blood pressure of ≤50 mmHg)
- •Initiation, discontinuation, or change of dosing of prophylactic medications within 2 months prior to study inclusion
- •Intake of acute medications (e.g. analgesics, triptans) within 48 hours of infusion start
- •Headache of any intensity within 48 hours of infusion start
- •Aura within 48 hours of infusion start
研究组 & 干预措施
Pituitary Adenylate Cyclase Activating Polypeptide-38 (PACAP-38)
PACAP-38 will be administered by intravenous infusion.
干预措施: Pituitary Adenylate Cyclase Activating Polypeptide-38 (PACAP-38) (Drug)
Placebo
Placebo (isotonic saline) will be administered by intravenous infusion.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of migraine attacks with aura
时间窗: 12 hours
Difference in incidence of migraine attack with aura between PACAP-38 and placebo during the 12-hour observational period after infusion start. Experimentally induced migraine aura is defined as aura that meet Criteria B and C of 1.2 Migraine with Aura in ICHD-3.
次要结局
- Incidence of migraine attacks without aura(12 hours)
- Headache intensity scores(12 hours)
研究者
Haidar Al-Khazali
Principal Investigator
Danish Headache Center