Clinical trial NCT00424970: Treatment of High Altitude Polycythemia by Acetazolamide
Official title: Hypoventilation and High Altitude Chronic Polycythemia: Acetazolamide as a Possible Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: High Altitude Polycythemia
Keywords: high altitude
hypoxia
pulmonary hypertension
polycythemia
hypoventilation
Lead sponsor: Association pour la Recherche en Physiologie de l'Environnement
Sponsor class: OTHER
Collaborators: name: University of Paris 13
name: Universidad Peruana Cayetano Heredia
name: Legs Poix
First posted: 2007-01-22
Enrollment: 55
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

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

Primary outcomes:
measure: Hemoglobin concentration
timeFrame: monthly
measure: Hematocrit
timeFrame: monthly
Secondary outcomes:
measure: Systolic pulmonary arterial pressure
timeFrame: before and after 3 months of treatment
measure: Pulmonary vascular resistance
timeFrame: before and after 3 months of treatment
measure: Arterial oxygen saturation at rest
timeFrame: monthly
measure: Clinical score of Chronic Mountain Sickness
timeFrame: monthly
measure: Quality of lofe score
timeFrame: monthly
Other outcomes:
Locations:
city: Lima
country: Peru
facility: University Cayetano Heredia
Study officials:
affiliation: ARPE, University Paris 13
name: Jean-Paul Richalet, MD, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Cayetano Heredia, Lima, Peru
name: Fabiola Leon-Velarde, PHD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.