Clinical trial NCT02811016: Inhaled Budesonide and Acute Mountain Sickness
Official title: Effect of Inhaled Budesonide on the Incidence and Severity of Acute Mountain Sickness at 4559 m
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Mountain Sickness
Keywords: High Altitude
budesonide
hypoxia
Lead sponsor: Salzburger Landeskliniken
Sponsor class: OTHER
Collaborators: name: University Hospital Heidelberg
First posted: 2016-06-23
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of acute mountain sickness
timeFrame: 48 hrs at 4559 m
Secondary outcomes:
measure: Severity of acute mountain sickness
timeFrame: 48 hrs at 4559 m
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: Department of Anesthesiology, University Hospital
Study officials:
affiliation: Department of Anesthesiology, University Hospital Salzburg
name: Marc M Berger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.