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

Mountain Sickness Clinical Trial

— CoCMS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01187108
• Other study ID #: 10-0078
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 18, 2010
• Last updated: May 13, 2015
• Start date: June 2013
• Est. completion date: September 2013

Study information

• Verified date: May 2015
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardPeru: Universidad Peruana Cayetano Heredia
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Altitude Sickness
• Erythrocytosis
• Mountain Sickness
• Polycythemia

Intervention

Drug:
• N-acetylcysteine
NAC 600 mg oral once daily
• Acetazolamide
Acetazolamide 250 mg oral once daily
• Placebo pills
1 (or 2 in the placebo group) empty gel capsules

Locations

Country	Name	City	State
Peru	Chronic mountain sickness clinic	Cerro de Pasco	Pasco

Sponsors (4)

Lead Sponsor	Collaborator
University of Colorado, Denver	Jackson, Brian, M.S., Thomas H Maren Foundation, Universidad Peruana Cayetano Heredia

Country where clinical trial is conducted

Peru, 

References & Publications (3)

Jefferson JA, Escudero E, Hurtado ME, Kelly JP, Swenson ER, Wener MH, Burnier M, Maillard M, Schreiner GF, Schoene RB, Hurtado A, Johnson RJ. Hyperuricemia, hypertension, and proteinuria associated with high-altitude polycythemia. Am J Kidney Dis. 2002 Jun;39(6):1135-42. — View Citation

Jefferson JA, Escudero E, Hurtado ME, Pando J, Tapia R, Swenson ER, Prchal J, Schreiner GF, Schoene RB, Hurtado A, Johnson RJ. Excessive erythrocytosis, chronic mountain sickness, and serum cobalt levels. Lancet. 2002 Feb 2;359(9304):407-8. — View Citation

Richalet JP, Rivera-Ch M, Maignan M, Privat C, Pham I, Macarlupu JL, Petitjean O, León-Velarde F. Acetazolamide for Monge's disease: efficiency and tolerance of 6-month treatment. Am J Respir Crit Care Med. 2008 Jun 15;177(12):1370-6. doi: 10.1164/rccm.200802-196OC. Epub 2008 Apr 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Change from baseline Erythropoietin at week 8	Serum hormone that stimulates red blood cell production	Baseline and week 8	No
Secondary	Change from baseline in serum and urine Cobalt at day 3	Will calculate spot clearance of cobalt	Baseline and day 3	No
Secondary	Change in baseline urine protein at 8 weeks	Ratio of urine total protein to urine creatinine	Baseline and week 8	No
Secondary	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	Yes
Secondary	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	Yes