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

Sponsor

University of Colorado, Denver (Other)

Overall Status

Completed

CT.gov ID

NCT01187108

Collaborator

Universidad Peruana Cayetano Heredia (Other), Jackson, Brian, M.S. (Other), Thomas H Maren Foundation (Other)

Enrollment

Location

Arms

Duration (Months)

28.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Erythrocytosis Mountain Sickness	Drug: N-acetylcysteine Drug: Acetazolamide Drug: Placebo pills	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

85 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2013

Actual Primary Completion Date :

Sep 1, 2013

Actual Study Completion Date :

Sep 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Change from baseline in Hematocrit, or fraction of plasma occupied by cellular elements at week 8 [Baseline and week 8]
Spun hematocrit measured on portable machine

Secondary Outcome Measures

Change from baseline in arterial blood gas values at week 8 [Baseline and week 8]
Analyzed using portable machine. The values analyzed include serum pH, partial pressure of carbon dioxide, partial pressure of oxygen, and serum bicarbonate.
Change from baseline Erythropoietin at week 8 [Baseline and week 8]
Serum hormone that stimulates red blood cell production
Change from baseline in serum and urine Cobalt at day 3 [Baseline and day 3]
Will calculate spot clearance of cobalt
Change in baseline urine protein at 8 weeks [Baseline and week 8]
Ratio of urine total protein to urine creatinine
Change in baseline Chronic mountain sickness score at 8 weeks [Baseline and week 8]
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
Changes in baseline Serum electrolytes at day 3, 14 and week 8 [Baseline and Days 3, 14, and week 8]
Electrolytes, specifically monitoring serum potassium to treat serious hypokalemia (serum potassium < 3.0 meQ/L).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chronic mountain sickness clinic	Cerro de Pasco	Pasco	Peru

Sponsors and Collaborators

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

Investigators

Principal Investigator: Richard Johnson, MD, University of Colorado Denver Health Sciences Center
Principal Investigator: Abdias Hurtado, MD, Universidad Peruana Cayetano Heredia
Study Director: Richard Fuquay, MD, University of Colorado Denver Health Sciences Center