Treatment of High Altitude Polycythemia by Acetazolamide

Hypoventilation and High Altitude Chronic Polycythemia: Acetazolamide as a Possible Treatment

The prevalence of High Altitude Polycythemia (or Chronic Mountain Sickness) is between 8 and 15% in the high altitude regions of South America. There is no pharmacological treatment available. After a first preliminary study in 2003 demonstrating the beneficial effects of acetazolamide in reducing hematocrit in these patients, after 3 weeks of treatment, we want to confirm this effect and implement a treatment protocol of 3 month-duration.

Study Overview

• Status: Completed
• Conditions: High Altitude Polycythemia
• Intervention / Treatment: Drug: acetazolamide

Detailed Description

Chronic mountain sickness (CMS) is characterized by an excessive number of red cells in the blood of persons living permanently above the altitude of 2,500m. The symptoms of this very incapacitating disease are : headaches, chronic asthenia, digestive troubles, sleep disturbances. The hemoglobin concentration is higher than 21 g/dl of blood. In addition, patients show a pulmonary hypertension of variable degree, as well as a systemic hypertension.

This disease affects essentially males, but women are also concerned after menopause. The evolution of the disease is always very dramatic, towards a cardiac failure and cerebral vascular stroke. The prevalence is between 8% and 15% on the Andean Altiplano . No pharmacological treatment is available.

A preliminary study was performed (Richalet et al. AJRCCM, 2005) that demonstrated the efficiency of acetazolamide (a carbonic anhydrase inhibitor) in reducing the hematocrit and the erythropoetin concentration,and increasing nocturnal oxygen saturation in patients suffering from CMS, after 3 weeks of treatment.

We plan to perform a double-blinded placebo-controlled study to evaluate the efficiency of a 3-month treatment with daily 250 mg acetazolamide to reduce the hematocrit and hemoglobin concentrations and ameliorate the clinical symptoms of 55 patients suffering from CMS and living at high altitude (Cerro de Pasco, Peru).

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 4

Contacts and Locations

Study Locations

• Peru
  • Lima, Peru, 100
    • University Cayetano Heredia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• patients with Chronic mountain sickness and Hb > 21g/dl

Exclusion Criteria:

• patients smokers
• patients with respiratory or cardiovascular or renal disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: acetazolamide; acetazolamide 250mg /day oral administration, for 6 months	Drug: acetazolamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Hemoglobin concentration	monthly
Hematocrit	monthly

Secondary Outcome Measures

Outcome Measure	Time Frame
Systolic pulmonary arterial pressure	before and after 3 months of treatment
Pulmonary vascular resistance	before and after 3 months of treatment
Arterial oxygen saturation at rest	monthly
Clinical score of Chronic Mountain Sickness	monthly
Quality of lofe score	monthly

Collaborators and Investigators

• Sponsor: Association pour la Recherche en Physiologie de l'Environnement
• Collaborators: Universidad Peruana Cayetano Heredia; University of Paris 13; Legs Poix
• Investigators: Principal Investigator: Jean-Paul Richalet, MD, PHD, ARPE, University Paris 13; Study Director: Fabiola Leon-Velarde, PHD, University Cayetano Heredia, Lima, Peru

Publications and helpful links

General Publications

• Richalet JP, Rivera M, Bouchet P, Chirinos E, Onnen I, Petitjean O, Bienvenu A, Lasne F, Moutereau S, Leon-Velarde F. Acetazolamide: a treatment for chronic mountain sickness. Am J Respir Crit Care Med. 2005 Dec 1;172(11):1427-33. doi: 10.1164/rccm.200505-807OC. Epub 2005 Aug 26.
• Maignan M, Rivera-Ch M, Privat C, Leon-Velarde F, Richalet JP, Pham I. Pulmonary pressure and cardiac function in chronic mountain sickness patients. Chest. 2009 Feb;135(2):499-504. doi: 10.1378/chest.08-1094. Epub 2008 Aug 21.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Study Completion (Actual): November 1, 2007

Study Registration Dates

• First Submitted: January 19, 2007
• First Submitted That Met QC Criteria: January 19, 2007
• First Posted (Estimate): January 22, 2007

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: pulmonary hypertension; hypoxia; high altitude; hypoventilation; polycythemia
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Hematologic Diseases; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Altitude Sickness; Hypoventilation; Polycythemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: APCA06; Legs Poix 999