Effect of Acetazolamide on Sleep Disordered Breathing in Lowlanders Older Than 40 Years at Altitude

Sponsor

University of Zurich (Other)

Overall Status

Completed

CT.gov ID

NCT03536507

Collaborator

National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov (Other)

185

Enrollment

Location

Arms

2.6

Actual Duration (Months)

71.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Randomized, placebo controlled trial evaluating the effect of acetazolamide on sleep disordered breathing in lowlanders older than 40 years travelling from 760 m to 3'100 m.

Condition or Disease	Intervention/Treatment	Phase
Altitude Hypoxia	Drug: ACETAZOLAMIDE oral capsule Drug: Placebo oral capsule	Phase 4

Detailed Description

This is a randomized, placebo-controlled, double-blind parallel trial evaluating the effect of preventive acetazolamide intake on the sleep disordered breathing in lowlanders older than 40 years travelling to altitude. Participants living in the Bishkek area, Kyrgyzstan (760m), will be transferred by car within 4h to the Tuja Ashu high altitude clinic (3'100 m), and stay there for 2 days. Acetazolamide 375mg/day (or placebo), will be administered before departure at 760 m and during the stay at altitude. Outcomes will be assessed during the stay at 3'100 m.

An interim analysis will be carried out when 80 participants will have completed the study or after the first year. The Peto's method will be used and the trial will be stopped when pre-specified futility boundaries were crossed.

Study Design

Study Type:

Interventional

Actual Enrollment :

185 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Effect of Acetazolamide on Sleep Disordered Breathing in Lowlanders Older Than 40 Years at Altitude: A Randomized, Placebo-controlled, Double-blind Parallel Trial

Actual Study Start Date :

May 15, 2018

Actual Primary Completion Date :

Aug 2, 2018

Actual Study Completion Date :

Aug 2, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ACETAZOLAMIDE oral capsule Acetazolamide 375mg/day (capsule @125 mg: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3'100m until the morning after the second night at 3'100m	Drug: ACETAZOLAMIDE oral capsule Administration of 1x125mg acetazolamide in the morning, 2x125mg in the evening, starting 24 hours before departure to 3'100m
Placebo Comparator: PLACEBO oral capsule Placebo (capsules identically looking as acetazolamide capsules: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3'100m until the morning after the second night at 3'100m	Drug: Placebo oral capsule Administration of equally looking placebo capsules in the morning and evening, starting 24 hours before departure to 3'100m

Arm

Intervention/Treatment

Active Comparator: ACETAZOLAMIDE oral capsule

Acetazolamide 375mg/day (capsule @125 mg: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3'100m until the morning after the second night at 3'100m

Drug: ACETAZOLAMIDE oral capsule

Administration of 1x125mg acetazolamide in the morning, 2x125mg in the evening, starting 24 hours before departure to 3'100m

Placebo Comparator: PLACEBO oral capsule

Placebo (capsules identically looking as acetazolamide capsules: 1 in the morning, 2 in the evening), orally. Medication starts 24 hours before ascent to 3'100m until the morning after the second night at 3'100m

Drug: Placebo oral capsule

Administration of equally looking placebo capsules in the morning and evening, starting 24 hours before departure to 3'100m

Outcome Measures

Primary Outcome Measures

Change in nocturnal oxygen desaturation index [night 1 at 760m and night 1 at 3'100 m]
Difference in altitude-induced change in the mean number of cyclic dips in oxygen saturation measured by pulse oximetry between acetazolamide and placebo group

Secondary Outcome Measures

Change in nocturnal oxygen saturation night 1 at 3'100m [night 1 at 760m and night 1 at 3'100 m]
Difference in altitude-induced change in mean nocturnal oxygen saturation measured by pulse oximetry between acetazolamide and placebo group
Change in nocturnal oxygen saturation night 2 at 3'100m [night 1 at 760m and night 2 at 3'100 m]
Difference in altitude-induced change in mean nocturnal oxygen saturation measured by pulse oximetry between acetazolamide and placebo group
Change in nocturnal oxygen desaturation index [night 1 at 760m and night 2 at 3'100 m]
Difference in altitude-induced change in the mean number of cyclic dips in oxygen saturation measured by pulse oximetry between acetazolamide and placebo group
Change in apnea/hypopnea index night 1 at 3'100m [night 1 at 760m and night 1 at 3'100 m]
Difference in altitude-induced change in mean number of apneas/hypopneas per hour between the acetazolamide and placebo group
Change in apnea/hypopnea index night 2 at 3'100m [night 1 at 760m and night 2 at 3'100 m]
Difference in altitude-induced change in mean number of apneas/hypopneas per hour between the acetazolamide and placebo group
Change in subjective sleepiness and sleep quality [Day 1 and 2 at 760m and 3'100m]
Difference in altitude-induced change in subjective sleepiness and sleep quality assessed by a visual analog scale between acetazolamide and placebo group

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy men and women, age 40-75 yrs, without any disease and need of medication.
Born, raised and currently living at low altitude (<800m).
Written informed consent.
Kyrgyz ethnicity

Exclusion Criteria:

Any active respiratory, cardiovascular or other disease requiring regular treatment or being otherwise relevant for tolerance of hypoxia or altitude exposure.
Any condition that may interfere with protocol compliance including current heavy smoking (>20 cigarettes per day or >20 pack-years with active smoking during the last 10 years), regular use of alcohol.
Allergy to acetazolamide and other sulfonamides.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Center of Cardiology and Internal Medicine	Bishkek		Kyrgyzstan	720040

Sponsors and Collaborators

University of Zurich
National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov

Investigators

Study Chair: Konrad E Bloch, MD, University Hospital, Zürich
Study Director: Talant M Sooronbaev, MD, National Center of Cardiology and Internal Medicine, Bishkek, Kyrgyzstan
Principal Investigator: Michael Furian, MSc, University Hospital, Zürich