Calcitonin Gene-Related Peptide Antibody for Prevention of Acute Mountain Sickness: A Prospective Single-center, Randomized, Placebo-controlled, Double-blinded Study
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Severity of acute mountain sickness as measured by the Lake Louise Score (LLS)
研究概览
简要总结
Acute mountain sickness (AMS) is a common condition that can occur when healthy people travel quickly to high altitude. Typical symptoms include headache, nausea, tiredness, dizziness, and poor sleep. In most cases, AMS improves with rest and by not climbing higher, but it can make mountaineering difficult and, in severe cases, can lead to dangerous complications.
The biological mechanisms that cause high-altitude headache and AMS are not yet fully understood. Some symptoms of AMS are similar to migraine, suggesting that both conditions may share common pathways in the nervous system. One possible pathway involves calcitonin gene-related peptide (CGRP), a substance known to play an important role in migraine.
Fremanezumab is an approved monoclonal antibody used to prevent migraine. It works by binding to CGRP and reducing its biological activity. This study will investigate whether a single dose of fremanezumab can also help prevent symptoms of AMS and high-altitude headache in healthy adults exposed to high altitude. To date, there are no clinical data on the effect of fremanezumab in AMS or high-altitude headache.
This is a prospective, randomized, double-blind, placebo-controlled, parallel-group clinical trial. A total of 30 healthy adult volunteers will participate. Participants will be randomly assigned in a 1:1 ratio to receive either a single subcutaneous injection of fremanezumab 225 mg or placebo (saline). Neither the participants nor the investigators will know which treatment was given during the study. The study medication will be administered 1 week before ascent to Capanna Regina Margherita at 4554 meters above sea level. Participants will remain there for 46 hours under hypobaric hypoxic conditions.
The main goal is to determine whether fremanezumab reduces the severity of AMS compared with placebo. AMS symptoms will be measured using the Lake Louise Score, a standard questionnaire commonly used in altitude medicine. Additional assessments will include the incidence of AMS, headache characteristics, safety outcomes, vital signs, oxygen saturation, and the use of rescue medication. Symptoms will be assessed repeatedly during the high-altitude stay.
Only healthy adults aged 18 to 60 years living below 1000 meters will be eligible. People with important medical conditions, chronic headache or migraine, relevant cardiovascular or lung disease, pregnancy, or recent high-altitude exposure will be excluded. Participants will be closely monitored during the study. Rescue medication, oxygen, and descent to lower altitude will be available if needed.
This study may help improve understanding of how AMS develops and whether CGRP blockade could become a new preventive strategy for high-altitude headache and AMS. It may also improve understanding of links between altitude-related headache and migraine.
详细描述
cute mountain sickness (AMS) is a common condition that occurs in otherwise healthy individuals after rapid ascent to high altitude. Typical symptoms include headache, nausea, vomiting, fatigue, dizziness, and loss of appetite. In most cases, AMS is self-limiting if further ascent is avoided and sufficient rest is ensured. However, AMS can substantially impair well-being and performance at altitude, may lead to interruption of a mountain tour, and in more severe cases may require rescue or evacuation. Rarely, AMS may progress to life-threatening high-altitude cerebral edema. High-altitude headache (HAH) is one of the core symptoms of AMS and is particularly frequent at high altitude.
The biological mechanisms underlying HAH and AMS are not yet fully understood. Clinical features of HAH and AMS, especially headache accompanied by nausea and vomiting, suggest overlap with migraine pathophysiology. One possible mechanistic link is the trigeminovascular system and the neuropeptide calcitonin gene-related peptide (CGRP), which is known to play a major role in migraine. Fremanezumab is a monoclonal antibody approved for migraine prevention. It binds to CGRP and prevents its biological activity. Because CGRP may also be involved in vascular and neurogenic responses to hypoxia, CGRP blockade could potentially influence the development of high-altitude symptoms. At present, there are no clinical data on the effect of fremanezumab in HAH or AMS.
The aim of this study is to investigate whether a single dose of fremanezumab can reduce the severity and incidence of AMS in healthy adults exposed to high altitude under controlled field conditions. In addition, the study will assess whether CGRP blockade influences headache characteristics and safety outcomes during prolonged exposure to hypobaric hypoxia. The study may also contribute to a better understanding of shared mechanisms between altitude-related headache and migraine.
This is a prospective, randomized, double-blind, placebo-controlled, parallel-group, exploratory clinical trial in healthy adult volunteers. A total of 30 participants will be enrolled and randomized in a 1:1 ratio to receive either fremanezumab 225 mg or placebo (0.9% saline solution) as a single subcutaneous injection. The study medication will be administered 1 week before ascent to high altitude. Participants, investigators, care providers, outcome assessors, and data analysts will remain blinded to treatment allocation until database lock, except in case of medical emergency requiring unblinding.
Participants will undergo screening before enrolment, including informed consent, medical assessment, and confirmation of eligibility. Eligible participants are healthy adults aged 18 to 60 years, living below 1000 meters above sea level, and able to comply with study procedures. Key exclusion criteria include chronic headache or migraine, cardiovascular disease other than controlled hypertension, acute or chronic pulmonary disease, diabetes mellitus, marked hypertension, pregnancy or breastfeeding, recent high-altitude exposure, and other relevant medical conditions that could interfere with safety or interpretation of the study data. Both sexes will be included, with the aim of balanced representation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-60 years
- •No relevant previous illnesses in the preliminary examination
- •Written consent to participate in the study
- •Permanent residence <1000 m
- •Men and women are included without prioritization
- •Negative urine pregnancy test if pregnancy cannot be ruled out with certainty
排除标准
- •Intolerance / allergy to Fremanzeumab or other drug components
- •Acute or chronic lung disease
- •Blood pressure systolic ≥150 mmHg or diastolic ≥95 mmHg (average of two measurements) in subjects with or without blood pressure medication
- •Pre-existing cardiovascular diseases other than arterial hypertension (coronary heart disease, heart failure, pulmonary hypertension, atrial fibrillation, peripheral arterial occlusive disease)
- •Chronic headache, migraine
- •Diabetes mellitus
- •Smoking (>6 cigarettes/d) or equivalent nicotine substitution
- •Alcohol (>30 g/d) or other drug abuse
- •Overweight (BMI >30 kg/m2)
- •Other pre-existing conditions considered relevant by the investigators (liver disease, kidney disease, thyroid disease, Parkinson's disease, pheochromocytoma)
- •Stay >2000 m altitude within the last 8 weeks before the first study day
- •Medication taken within the last 2 months before the first study day, which could influence the data quality (e.g. corticosteroids) or the safety of the subjects (e.g. anticoagulation).
- •Blood donation within the last 2 months before the first study day
- •Pregnancy or breastfeeding
- •Participation in other clinical studies
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
CGRP antibody
干预措施: Fremanezumab 225 Mg/1.5 mL Subcutaneous Solution (Drug)
结局指标
主要结局
Severity of acute mountain sickness as measured by the Lake Louise Score (LLS)
时间窗: after 7, 22, 31, and 46 hours of exposure to hypobaric hypoxia at an altitude of 4,554 m
The Lake Louise Score is a validated symptom-based scoring system used to assess acute mountain sickness (AMS). It evaluates the presence and severity of typical AMS symptoms, including headache, gastrointestinal symptoms, fatigue or weakness, dizziness or light-headedness, and sleep disturbance. Each symptom is rated on a scale from 0 to 3, where 0 indicates absence of the symptom and 3 indicates severe symptoms. The total score ranges from 0 to 15, with higher scores indicating more severe AMS symptoms. In this study, the Lake Louise Score will be used to assess the incidence and severity of acute mountain sickness during exposure to high altitude. AMS is typically defined as the presence of headache together with a total Lake Louise Score of 3 or higher.
次要结局
未报告次要终点