Inhaled Budesonide and Acute Mountain Sickness

Effect of Inhaled Budesonide on the Incidence and Severity of Acute Mountain Sickness at 4559 m

The primary objective of the study is to investigate the effect of inhaled budesonide on the incidence of AMS. The primary study question to ask is:

1. Does inhaled budesonide reduce the incidence of AMS after rapid and active ascent to 4559 m?

In addition, the secondary study questions to ask are:

1. Does inhaled budesonide reduce the severity of AMS after rapid and active ascent to 4559 m?
2. Are the effects of inhaled budesonide on AMS incidence and severity related to its plasma concentration?

Study medication Inhaled budesonide at 2 different concentrations (2 x 200 µg, 2 x 800 µg) versus placebo

Study design

• Prospective, controlled, single-center study on 51 healthy volunteers at 4559 m [Capanna Regina Margherita (Margherita Hut), Italy]
• With regard to the intervention (inhaled budesonide) double-blinded and randomized

Study Overview

• Status: Completed
• Conditions: Acute Mountain Sickness
• Intervention / Treatment: Drug: Budesonide 200; Drug: Budesonide 800; Drug: Placebo

Detailed Description

Primary objective

The primary objective of the study is to investigate the effect of inhaled budesonide on the incidence of AMS. The primary study question to ask is:

1. Does inhaled budesonide reduce the incidence of AMS after rapid and active ascent to 4559 m?

In addition, the secondary study questions to ask are:

1. Does inhaled budesonide reduce the severity of AMS after rapid and active ascent to 4559 m?
2. Are the effects of inhaled budesonide on AMS incidence and severity related to its plasma concentration?

Study medication Inhaled budesonide at 2 different concentrations (2 x 200 µg, 2 x 800 µg) versus placebo

Study design Prospective, controlled, single-center study on 51 healthy volunteers at 4559 m [Capanna Regina Margherita (Margherita Hut), Italy] With regard to the intervention (inhaled budensoide) double-blinded and randomized

Study population 51 healthy volunteers

Study site Prior to the study the pre-investigations will be performed at the University Hospital Salzburg, Austria. The high-altitude part will take place at the Capanna Regina Margherita (Margherita Hut, Italy) at 4559 m.

Interventions and investigations

• Ascend from Alagna (1130 m, Italy) to the Margherita Hut (4559 m) in less than 24 h, with a preceding overnight stay at 3611 m (Gnifetti Hut, Italy).
• Stay at the Margherita Hut for 48 hours
• Randomized inhalation of budesonide at two different concentrations (2 x 200 µg 2 x 800 µg, respectively) or placebo
• Assessment of incidence and severity of acute mountain sickness by use of 2 internationally standardized and well established questionnaires
• Venous (and capillary) blood drawings
• Pulmonary function tests
• Transthoracic echocardiography for assessing pulmonary artery systolic pressure

Number and volume of blood drawings For the study venous blood samples (volume: 20 ml each) will be drawn at 5 different time points (5 x 20 ml = 100 ml). Together with the blood drawing for the pre-investigation (20 ml) a total blood volume of 120 ml will be taken. At the same time points capillary blood samples (1 ml) will be taken from the ear lobe for blood gas analyses (5 x 1 ml = 5 ml in total).

Observational period The study will only start after approval by the ethic committee responsible for the study (ethic committee of the Paracelsus Medical University). If the study is approved it will be performed in July 2016.

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Department of Anesthesiology, University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Good physical condition
• No relevant pathologies revealed by the pre-investigation prior to the study
• Written informed consent to participate in the study
• Permanent residency below 1000 m
• Males and females are included without prioritization

Exclusion Criteria:

• Acute and chronic lung diseases
• Conventional systolic blood pressure (average of two measurements) ≥150 mmHg and conventional diastolic blood pressure ≥95 mmHg in untreated or treated subjects
• Cardiovascular diseases other than hypertension (coronary heart disease, heart failure, atrial fibrillation, peripheral artery disease)
• Chronic headache / migraine
• Diabetes mellitus
• Smoking (>6 cigarettes/day) or equivalent nicotine substitutes
• Alcohol (>30 g/d) or drug abuse
• Obesity (Body Mass Index >30)
• Other conditions deemed relevant by the investigator (including liver disease, renal disease)
• Sojourn >2000 m within the last 4 weeks before the 1st study day
• Drug intake within the last 2 moth before the 1st study day if the drug intake could affect the data quality or the safety of the participants
• Blood donation within the last 2 month before the 1st study day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: budesonide 200; inhaled budesonide 200 µg bid	Drug: Budesonide 200; 200 µg inhaled at 7:00 a.m. and 7 p.m.; Other Names: Pulmicort Turbohaler
Experimental: budesonide 800; inhaled budesonide 800 µg bid	Drug: Budesonide 800; 800 µg inhaled at 7:00 a.m. and 7 p.m.; Other Names: Pulmicort Turbohaler
Placebo Comparator: placebo; inhaled placebo bid	Drug: Placebo; Placebo Inhalation at 7:00 a.m. and 7 p.m.; Other Names: Lactose-Monohydrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute mountain sickness	AMS scores positive	48 hrs at 4559 m

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of acute mountain sickness	Height of AMS scores	48 hrs at 4559 m

Collaborators and Investigators

• Sponsor: Salzburger Landeskliniken
• Collaborators: University Hospital Heidelberg
• Investigators: Principal Investigator: Marc M Berger, MD, Department of Anesthesiology, University Hospital Salzburg

Publications and helpful links

General Publications

• Berger MM, Macholz F, Sareban M, Schmidt P, Fried S, Dankl D, Niebauer J, Bartsch P, Mairbaurl H. Inhaled budesonide does not prevent acute mountain sickness after rapid ascent to 4559 m. Eur Respir J. 2017 Sep 10;50(3):1700982. doi: 10.1183/13993003.00982-2017. Print 2017 Sep. No abstract available.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 20, 2016
• First Posted (Estimate): June 23, 2016

Study Record Updates

• Last Update Posted (Estimate): October 14, 2016
• Last Update Submitted That Met QC Criteria: October 13, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: hypoxia; budesonide; High Altitude
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Altitude Sickness; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Budesonide
• Other Study ID Numbers: M2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No