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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
168
Suxiao Jiuxin Pill is a traditional Chinese medicine compound composed of Ligusticum Wallichii and Borneo Camphorwood, and its clinical safety has been confirmed. Traditional Chinese medicine theory believes that Suxiao Jiuxin Pill has the effects of promoting qi and blood circulation, removing blood stasis and relieving pain, which may help alleviate symptoms of AMS.
Placebo is made of less than 10% of the amount of Suxiao Jiuxin Pill, with similar dosage, odor, and taste.
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.
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.
Time frame: The next morning of arrival day at high altitude
Incidence rate of AMS assessed by LLS system after arrival at high altitude between Suxiao Jiuxin Pill and Placebo groups.
LLS assessments will be conducted before breakfast and before sleep after arrival at high altitude. The difference will be compared in the total incidence rates of AMS assessed by LLS after arrival between Suxiao Jiuxin Pill and Placebo groups.
Time frame: Arrival day to Day 3 after high altitude exposure
Baseline-corrected LLS after high altitude exposure between Suxiao Jiuxin Pill and Placebo groups.
LLS assessments will be conducted before breakfast and before sleep on Day 4 (at sea level) and the days after high altitude exposure. LLS on Day 4 will be used as baseline scores. The difference will be compared in the mean baseline-corrected LLS between Suxiao Jiuxin Pill and Placebo groups.
Time frame: Day 4 at sea level 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.
LLS assessments will be conducted before breakfast and before sleep on days after arrival. The AUC of LLS in the mean LLS score-time profile after arrival will be compared between Suxiao Jiuxin Pill and Placebo groups.
Time frame: 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.
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Moderate and above AMS is defined as LLS score ≥ 6. The difference will be compared in the incidence rates of moderate and above AMS on the next morning of arrival between Suxiao Jiuxin Pill and Placebo groups.
Time frame: The next morning of arrival day at high altitude
Mean AMS Clinical Functional Score after arrival between Suxiao Jiuxin Pill and Placebo groups.
Self-reported AMS Clinical Functional Score is used to evaluate the impact of AMS symptoms on overall function at high altitude. The difference will be compared in the AMS Clinical Functional Scores after arrival between Suxiao Jiuxin Pill and Placebo groups.
Time frame: 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.
Blood oxygen saturation (SpO2) will be tested using a pulse oximetry and measured from the left index finger. SpO2 will be tested for 3 times daily by staff before breakfast, before lunch, and before sleep from Day 4 at sea level to Day 3 after high altitude exposure. The difference will be compared in SpO2 from sea level to high altitude between Suxiao Jiuxin Pill and Placebo groups.
Time frame: 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.
AMS symptoms requiring additional treatment is defined as high-altitude cerebral edema, high-altitude pulmonary edema, and severe AMS symptoms (nausea, vomiting, fatigue, dizziness, etc.). The difference will be compared in the incidence rates of AMS symptoms requiring additional treatment during and after high altitude exposure between Suxiao Jiuxin Pill and Placebo groups.
Time frame: Arrival day to Day 3 after high altitude exposure
Acute Mountain Sickness Symptom Scale and Score after arrival between Suxiao Jiuxin Pill and Placebo groups.
Acute Mountain Sickness Symptom Scale and Score is a scoring system which evaluates symptoms of headache, vomiting, dizziness, nausea, palpitation, shortness of breath, chest tightness, dizziness, insomnia, drowsiness, loss of appetite, abdominal distention, diarrhea, constipation, cyanosis of the lips, numbness of the hands and feet. The Acute Mountain Sickness Symptom Scale and Score assessments will be conducted before breakfast and before sleep from arrival day to Day 3 after high altitude exposure. The difference will be compared in the mean Acute Mountain Sickness Symptom Scale and Score after arrival between Suxiao Jiuxin Pill and Placebo groups.
Time frame: Arrival day to Day 3 after high altitude exposure
Rate of oxygen treatment after arrival between Suxiao Jiuxin Pill and Placebo groups.
Oxygen treatment will be given according to the participants' requirement or care providers' suggestion. The difference will be compared in the rates of oxygen treatment after arrival between Suxiao Jiuxin Pill and Placebo groups.
Time frame: Arrival day to Day 3 after high altitude exposure