Safety and Efficacy of Suxiao Jiuxin Pill for Prevention of Acute Mountain Sickness: a Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 168
- 主要终点
- Incidence rate of AMS assessed by LLS system on the next morning of arrival day at high altitude between Suxiao Jiuxin Pill and Placebo groups.
研究概览
简要总结
The aim of this randomized, controlled trial is to evaluate the safety and efficacy of Suxiao Jiuxin Pills for prevention of acute mountain sickness (AMS) after high altitude exposure in healthy volunteers, and its influences on physiological indicators before and after high altitude exposure.
详细描述
Acute altitude illness refers to a group of clinical symptoms that occur when travelers are exposed to high altitude in a short period of time, due to the body's incomplete or dysregulated adaptation to hypoxic environment, which may occur at anytime from a few hours to 5 days after ascending, with severity ranging from mild discomfort to life-threatening conditions such as cerebral and pulmonary edema. AMS is the most common manifestation, characterized by headache, gastrointestinal symptoms, fatigue, weakness, dizziness, light-headedness, etc. Lake Louise Score (LLS) system has been widely used to evaluate AMS, and the version updated in 2018 kept nausea/vomiting, fatigue, lassitude and dizziness as the assessment symptom for AMS, and each symptom can be scored as 0-3 according to severity. AMS can be diagnosed when headache exist and total LLS is ≥ 3 points. Based on total scores, AMS can be defined as mild (3-5), moderate (6-9) and severe (10-12).
Suxiao Jiuxin Pill is a traditional Chinese medicine compound composed of Ligusticum Wallichii and Borneo Camphorwood, and its clinical safety has been confirmed. A total of 168 subjects will be enrolled in this randomized, controlled trial, and eligible subjects will be randomized into Suxiao Jiuxin Pill intervention group or Placebo group after informed consent is obtained. The study drug or placebo will be given orally for 4 days at sea level, arrival day and another 2 days at high altitude. The clinical assessments, including LLS system, sleep questionnaire scores, vital signs, blood oxygen saturation, blood routine test, blood biochemistry test, echocardiogram, Holter, ambulatory blood pressure monitoring, pulse wave velocity, and transcranial Doppler ultrasound parameters will be repeatedly performed at sea level and high altitude.
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)
盲法说明
The participants, care providers, investigators, and outcome assessors will be blinded throughout the clinical trial. To ensure blindness, the experimental drug and placebo will be similar in dosage, odor, and taste. Suxiao Jiuxin Pill and placebo will be repackaged and distributed according to standardized procedures.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers, aged 18-55 years old (including boundary values);
- •Female volunteers weighing ≥45.0 kg and male volunteers weighing ≥50.0 kg, with a body mass index (BMI) between 19.0 and 28.0 kg/m2 (including boundary values) (BMI=weight kg/height m2);
- •Primary residence at an altitude of <500 meters above sea level;
- •Not ascending to an altitude >2500 meters in the 6 months prior to the screening period;
- •Voluntary participation with written informed consent.
排除标准
- •Subjects with previous severe high altitude sickness such as high altitude heart disease, high altitude pulmonary edema, high altitude cerebral edema, and high altitude erythrocytosis;
- •Subjects with established cardiovascular or cerebrovascular disease or uncontrolled hypertension (systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg at screening);
- •Subjects with clinically significant respiratory disease, digestive disease, liver disease, central nervous system disease, psychiatric disease, metabolic disease, renal disease, anemia, or acute infection;
- •Subjects with primary headache (migraine, tension headache, cluster headache, etc.) or secondary headache (headache associated with infection, cerebrovascular, etc.) within 1 month prior to screening;
- •Subjects with insomnia, anxiety, depression or a history of motion sickness or airplane sickness;
- •Subjects with Lake Louise Score ≥ 2 at screening;
- •Subjects with left index finger oxygen saturation <95% at screening;
- •Subjects with alanine aminotransferase or aspartate aminotransferase > 2 times the upper limit of the normal range, or creatinine > upper limit of the normal range at screening;
- •Subjects with hypersensitive C-reactive protein > upper limit of normal range at screening;
- •Subjects with history of surgery or blood donation within 3 months prior to screening;
- •Subjects with any medication or non-pharmacological intervention (including dietary supplements) to prevent or treat acute mountain sickness within 14 days prior to screening;
- •Smoking ≥20 cigarettes per day within 3 months prior to screening;
- •Contraindications to the use of Suxiao Jiuxin Pill, such as allergies;
- •Women who are pregnant, breastfeeding, or have a positive pregnancy test (human chorionic gonadotropin test);
- •Alcohol abuse [more than 28 standard units of alcohol per week (1 standard unit contains 14 g of alcohol, e.g., 360 mL of beer, 45 mL spirit with 40% alcohol by volume, or 150 mL of wine)] or substance abuse within 6 months prior to screening;
- •Participation in another interventional clinical study within 3 months prior to screening;
- •Other conditions, in the opinion of the investigators, make participation in this study inappropriate.
研究组 & 干预措施
Experimental: Suxiao Jiuxin Pill group
Participants who are randomly assigned to Suxiao Jiuxin Pill group will receive Suxiao Jiuxin Pills (6 pills per time, 3 times a day, taken sublingually) for 4 days at sea level and another 3 days at high altitude.
干预措施: Suxiao Jiuxin Pill (Drug)
Placebo: Placebo group
Participants who are randomly assigned to Placebo group will receive placebo (6 pills per time, 3 times a day, taken sublingually) for 4 days at sea level and another 3 days at high altitude.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence rate of AMS assessed by LLS system on the next morning of arrival day at high altitude between Suxiao Jiuxin Pill and Placebo groups.
时间窗: The next morning of arrival day at high altitude
AMS was defined as LLS score ≥ 3 with headache and at least one of the symptoms of nausea or vomiting, fatigue, dizziness. The difference in incidence rate of AMS on the next morning of arrival day at high altitude is pre-specified as primary efficacy endpoint between Suxiao Jiuxin Pill and Placebo groups.
次要结局
- Rate of oxygen treatment after arrival between Suxiao Jiuxin Pill and Placebo groups.(Arrival day to Day 3 after high altitude exposure)
- Area under the curve (AUC) of LLS in the mean LLS score-time profile after arrival between Suxiao Jiuxin Pill and Placebo groups.(Arrival day to Day 3 after high altitude exposure)
- Incidence rate of moderate and above AMS on the next morning of arrival at high altitude between Suxiao Jiuxin Pill and Placebo groups.(The next morning of arrival day at high altitude)
- Mean AMS Clinical Functional Score after arrival between Suxiao Jiuxin Pill and Placebo groups.(Arrival day to Day 3 after high altitude exposure)
- Blood oxygen saturation (SpO2) from sea level to high altitude between Suxiao Jiuxin Pill and Placebo groups.(Day 4 at sea level to Day 3 after high altitude exposure)
- Incidence rate of AMS symptoms requiring additional treatment during and after high altitude exposure between Suxiao Jiuxin Pill and Placebo groups.(Arrival day to Day 3 after high altitude exposure)
- Incidence rate of AMS assessed by LLS system after arrival at high altitude between Suxiao Jiuxin Pill and Placebo groups.(Arrival day to Day 3 after high altitude exposure)
- Baseline-corrected LLS after high altitude exposure between Suxiao Jiuxin Pill and Placebo groups.(Day 4 at sea level to Day 3 after high altitude exposure)
- Acute Mountain Sickness Symptom Scale and Score after arrival between Suxiao Jiuxin Pill and Placebo groups.(Arrival day to Day 3 after high altitude exposure)