Study of Cobalt's Role in Excessive Erythrocytosis Among High Altitude Dwellers in Cerro de Pasco, Peru

Study Overview
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Brief Summary
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Chronic mountain sickness is characterized by excessive red blood cell production which causes sludging of the vascular system. This high viscosity blood causes heart failure, cognitive dysfunction, and strokes. The investigators hypothesize that cobalt which has been previously been shown to be an environmental pollutant worsens the overproduction of red blood cells. The investigators plan to conduct a 6 week trial in which acetazolamide (already shown to improve chronic mountain sickness) and N-acetylcysteine (a drug that removes cobalt from the blood) are evaluated in their potential to improve chronic mountain sickness.

Official Title
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Randomized Controlled Trial of N-acetylcysteine and Acetazolamide in Treatment of Chronic Mountain Sickness

Conditions
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Erythrocytosis, Mountain Sickness

Intervention / Treatment
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* Drug: N-acetylcysteine
* Drug: Acetazolamide
* Drug: Placebo pills


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males over 17 years of age Hematocrit > 70% Chronic Mountain Sickness score (CMS) > 6 Able to give informed consent and follow instructions in written Spanish Exclusion Criteria: CMS > 15 Underlying lung disease, smoking, or oxygen therapy Asthma (bronchospasm can be caused by N-acetylcysteine) Phlebotomy in last 3 months h/o adverse reaction to acetazolamide or N-acetylcysteine

Ages Eligible for Study
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Minimum Age: 18 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo pills<br> | Drug: Placebo pills<br>* 1 (or 2 in the placebo group) empty gel capsules<br>|
| Active Comparator: Acetazolamide alone<br> | Drug: Acetazolamide<br>* Acetazolamide 250 mg oral once daily<br>* Other names: Given in gel capsules;Drug: Placebo pills<br>* 1 (or 2 in the placebo group) empty gel capsules<br>|
| Active Comparator: N-acetylcysteine alone<br> | Drug: N-acetylcysteine<br>* NAC 600 mg oral once daily<br>* Other names: Given in gel capsules;Drug: Placebo pills<br>* 1 (or 2 in the placebo group) empty gel capsules<br>|
| Active Comparator: Combination of N-acetylcysteine and acetazolamide<br> | Drug: N-acetylcysteine<br>* NAC 600 mg oral once daily<br>* Other names: Given in gel capsules;Drug: Acetazolamide<br>* Acetazolamide 250 mg oral once daily<br>* Other names: Given in gel capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Hematocrit, or fraction of plasma occupied by cellular elements at week 8 | Spun hematocrit measured on portable machine | Baseline and week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in arterial blood gas values at week 8 | Analyzed using portable machine. The values analyzed include serum pH, partial pressure of carbon dioxide, partial pressure of oxygen, and serum bicarbonate. | Baseline and week 8 | 
| Change from baseline Erythropoietin at week 8 | Serum hormone that stimulates red blood cell production | Baseline and week 8 | 
| Change from baseline in serum and urine Cobalt at day 3 | Will calculate spot clearance of cobalt | Baseline and day 3 | 
| Change in baseline urine protein at 8 weeks | Ratio of urine total protein to urine creatinine | Baseline and week 8 | 
| Change in baseline Chronic mountain sickness score at 8 weeks | Chronic Mountain Sickness Score Absent Mild Moderate Severe Headache 0 +1 +2 +3 Dizziness 0 +1 +2 +3 Failing Memory 0 +1 +2 +3 Fatigue 0 +1 +2 +3 Breathlessness 0 +1 +2 +3 Sleep disturbances 0 +1 +2 +3 Tinnitus 0 +1 +2 +3 Anorexia 0 +1 +2 +3 Cyanosis of lips, face, or fingers 0 +1 +2 +3 Hyperemia or prominent capillaries conjunctivae or laryngopharynx 0 +1 +2 +3 | Baseline and week 8 | 
| Changes in baseline Serum electrolytes at day 3, 14 and week 8 | Electrolytes, specifically monitoring serum potassium to treat serious hypokalemia (serum potassium < 3.0 meQ/L). | Baseline and Days 3, 14, and week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cobalt, Excessive Erythrocytosis, Monge's Disease, Acetazolamide, N-acetylcysteine, Altitude Sickness, Chronic Mountain Sickness