Treatment of Chronic Mountain Sickness

Study Overview
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Brief Summary
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This study aims to assess the effect of two drugs for the treatment of chronic mountain sickness in highlanders.

Detailed Description
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About 100 million individuals reside at high altitude (>2500m) worldwide, with the largest populations of highlanders being found in South America (Andean), central Asia (Tibetan and Sherpa) and East Africa (Ethiopian). Despite unique adaptations to hypoxia in these populations, chronic mountain sickness (CMS) is a clinical syndrome which is observed in 5-33% of individuals residing permanently at high altitude.Several pharmacological approaches have been proposed in the treatment of EE and CMS. However, few studies show sufficient clinical evidence for safety and efficacy in CMS treatment and most highlanders with CMS remain untreated. The present project aims to better characterize chronic hypoxic responses in highlanders and to evaluate the interest of acetazolamide and statins as potential treatments for chronic mountain sickness.

Official Title
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Acetazolamide and Statins for the Treatment of Chronic Mountain Sickness in Highlanders: A Randomized Controlled Trial

Conditions
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Hypoxia, Altitude

Intervention / Treatment
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* Drug: Acetazolamide
* Drug: Atorvastatin
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Age between 18 and 55 yrs Body mass index <30kg/m² Born at >3500 m, living for >3 years at the local high altitude No diagnosis of cardiorespiratory, metabolic or neurological diseases No drug intake No smoker Chronic mountain sickness score ≥6 Exclusion Criteria: Diagnosis of cardiorespiratory, metabolic and neurological diseases Systolic > 130 mmHg and/or diastolic > 85 mmHg blood pressure Drug intake Smoker Chronic mountain sickness score <6

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetazolamide<br>Oral acetazolamide (250 mg/day) intake for 9 months | Drug: Acetazolamide<br>* Daily acetazolamide pill intake<br>* Other names: Diamox;|
| Experimental: Atorvastatin<br>Oral atorvastatin (40 mg/day) intake for 9 months | Drug: Atorvastatin<br>* Daily atorvastatin pill intake<br>|
| Placebo Comparator: Placebo<br>Oral placebo pill (daily) intake for 9 months | Drug: Placebo oral tablet<br>* Daily placebo pill intake<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hematocrit | Change in blood hematocrit value in percentage | Change from before to after 9 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic mountain sickness score | Chronic mountain sickness score (between 0 and 24, the higher the score the more severe the sickness) according to the available international scoring system | Change from before to after 9 months of treatment | 
| Macrovascular reactivity | Post-ischemia brachial artery dilation in % | Change from before to after 9 months of treatment | 
| Microvascular reactivity | Hyperthermic microvascular dilation in % | Change from before to after 9 months of treatment | 
| Hemoglobin mass | Total blood hemoglobin mass in mg | Change from before to after 9 months of treatment | 
| Pulmonary arterial pressure | Systolic and mean pulmonary arterial pressure in mmHg | Change from before to after 9 months of treatment | 
| Blood pressure | 24-hour systolic and diastolic blood pressure | Change from before to after 9 months of treatment | 
| Sleep recording | Hypopnea-apnea index reported in number of events per hour | Change from before to after 9 months of treatment |