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

• ClinicalTrials.gov Identifier: NCT03536507
• Recruitment Status: Completed
• First Posted: May 24, 2018
• Last Update Posted: November 5, 2021
• Sponsor: University of Zurich
• Collaborator: National Center of Cardiology and Internal Medicine named after academician M.Mirrakhimov
• Information provided by (Responsible Party): University of Zurich

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 (Clinical Trial)
• 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: August 2, 2018
• Actual Study Completion Date: August 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

Outcome Measures

Primary Outcome Measures :

1. Change in nocturnal oxygen desaturation index [ Time Frame: 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 :

1. Change in nocturnal oxygen saturation night 1 at 3'100m [ Time Frame: 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
2. Change in nocturnal oxygen saturation night 2 at 3'100m [ Time Frame: 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
3. Change in nocturnal oxygen desaturation index [ Time Frame: 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
4. Change in apnea/hypopnea index night 1 at 3'100m [ Time Frame: 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
5. Change in apnea/hypopnea index night 2 at 3'100m [ Time Frame: 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
6. Change in subjective sleepiness and sleep quality [ Time Frame: 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

• Ages Eligible for Study: 40 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Kyrgyzstan

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

More Information

• Responsible Party: University of Zurich
• ClinicalTrials.gov Identifier: NCT03536507
• Other Study ID Numbers: 2018-01-8/305C
• First Posted: May 24, 2018
• Last Update Posted: November 5, 2021
• Last Verified: November 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Zurich:

healthy participants older than 40 years; sleep disordered breathing; periodic breathing; prevention; acetazolamide

Additional relevant MeSH terms:

Respiratory Aspiration; Sleep Apnea Syndromes; Altitude Sickness; Hypoxia; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Signs and Symptoms, Respiratory; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Acetazolamide; Anticonvulsants; Carbonic Anhydrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Diuretics; Natriuretic Agents; Physiological Effects of Drugs