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

This study has been completed.
Sponsor:
Collaborators:
Abdias Hurtado, Elizabeth Escudero (Universidad Peruana Cayetano Heredia)
Jackson, Brian, M.S.
Thomas H Maren Foundation
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01187108
First received: August 18, 2010
Last updated: May 13, 2015
Last verified: May 2015
  Purpose

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 Intervention Phase
Erythrocytosis
Mountain Sickness
Drug: N-acetylcysteine
Drug: Acetazolamide
Drug: Placebo pills
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial of N-acetylcysteine and Acetazolamide in Treatment of Chronic Mountain Sickness

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Change from baseline in Hematocrit, or fraction of plasma occupied by cellular elements at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
    Spun hematocrit measured on portable machine


Secondary Outcome Measures:
  • Change from baseline in arterial blood gas values at week 8 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
    Serum hormone that stimulates red blood cell production

  • Change from baseline in serum and urine Cobalt at day 3 [ Time Frame: Baseline and day 3 ] [ Designated as safety issue: No ]
    Will calculate spot clearance of cobalt

  • Change in baseline urine protein at 8 weeks [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: No ]
    Ratio of urine total protein to urine creatinine

  • Change in baseline Chronic mountain sickness score at 8 weeks [ Time Frame: Baseline and week 8 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Days 3, 14, and week 8 ] [ Designated as safety issue: Yes ]
    Electrolytes, specifically monitoring serum potassium to treat serious hypokalemia (serum potassium < 3.0 meQ/L).


Enrollment: 85
Study Start Date: June 2013
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Given in gel capsules
Drug: Acetazolamide
Acetazolamide 250 mg oral once daily
Other Name: Given in gel capsules

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01187108

Locations
Peru
Chronic mountain sickness clinic
Cerro de Pasco, Pasco, Peru
Sponsors and Collaborators
University of Colorado, Denver
Abdias Hurtado, Elizabeth Escudero (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
  More Information

Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01187108     History of Changes
Other Study ID Numbers: 10-0078
Study First Received: August 18, 2010
Last Updated: May 13, 2015
Health Authority: United States: Institutional Review Board
Peru: Universidad Peruana Cayetano Heredia

Keywords provided by University of Colorado, Denver:
Cobalt
Excessive Erythrocytosis
Monge's Disease
Acetazolamide
N-acetylcysteine
Altitude Sickness
Chronic Mountain Sickness

Additional relevant MeSH terms:
Altitude Sickness
Lead Poisoning
Polycythemia
Chemically-Induced Disorders
Hematologic Diseases
Poisoning
Respiration Disorders
Respiratory Tract Diseases
Acetazolamide
Acetylcysteine
N-monoacetylcystine
Anti-Infective Agents
Anticonvulsants
Antidotes
Antioxidants
Antiviral Agents
Carbonic Anhydrase Inhibitors
Cardiovascular Agents
Central Nervous System Agents
Diuretics
Enzyme Inhibitors
Expectorants
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015