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

NCT01187108 | Completed Phase 1 DMC

• 1 other identifier: 10-0078
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

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.

Conditions

Erythrocytosis; Mountain Sickness

Keywords

Cobalt; Excessive Erythrocytosis; Monge's Disease; Acetazolamide; N-acetylcysteine; Altitude Sickness; Chronic Mountain Sickness

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change from baseline in arterial blood gas values at week 8

  Baseline and week 8

• Change from baseline Erythropoietin at week 8

  Baseline and week 8

• Change from baseline in serum and urine Cobalt at day 3

  Baseline and day 3

• Change in baseline urine protein at 8 weeks

  Baseline and week 8

• Change in baseline Chronic mountain sickness score at 8 weeks

  Baseline and week 8

Study Arms (4)

Placebo pills

PLACEBO COMPARATOR

Drug: Placebo pills

Acetazolamide alone

ACTIVE COMPARATOR

Drug: Acetazolamide; Drug: Placebo pills

N-acetylcysteine alone

ACTIVE COMPARATOR

Drug: N-acetylcysteine; Drug: Placebo pills

Combination of N-acetylcysteine and acetazolamide

ACTIVE COMPARATOR

Drug: N-acetylcysteine; Drug: Acetazolamide

Interventions

N-acetylcysteine DRUG

NAC 600 mg oral once daily

Also known as: Given in gel capsules

Combination of N-acetylcysteine and acetazolamide; N-acetylcysteine alone

Acetazolamide DRUG

Acetazolamide 250 mg oral once daily

Also known as: Given in gel capsules

Acetazolamide alone; Combination of N-acetylcysteine and acetazolamide

Placebo pills DRUG

1 (or 2 in the placebo group) empty gel capsules

Acetazolamide alone; N-acetylcysteine alone; Placebo pills

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Chronic mountain sickness clinic

Cerro de Pasco, Departamento de Pasco, Peru

Location

Related Publications (3)

• 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. doi: 10.1016/s0140-6736(02)07594-3.

  PMID: 11844517 BACKGROUND

• 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. doi: 10.1053/ajkd.2002.33380.

  PMID: 12046023 BACKGROUND

• Richalet JP, Rivera-Ch M, Maignan M, Privat C, Pham I, Macarlupu JL, Petitjean O, Leon-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.

  PMID: 18388356 BACKGROUND

MeSH Terms

Conditions

Polycythemia; Altitude Sickness

Interventions

Acetylcysteine; Gels; Acetazolamide

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Thiadiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Richard Johnson, MD

  University of Colorado Denver Health Sciences Center

  PRINCIPAL INVESTIGATOR

• Abdias Hurtado, MD

  Universidad Peruana Cayetano Heredia

  PRINCIPAL INVESTIGATOR

• Richard Fuquay, MD

  University of Colorado Denver Health Sciences Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2010
• First Posted: August 23, 2010
• Study Start: June 1, 2013
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: May 15, 2015

Record last verified: 2015-05

Locations

PE (1)