AT1R Blockade and Periodic Breathing During Sleep in Hypoxia
Effect of Angiotensin Receptor Blockers on Periodic Breathing During Sleep in Hypoxia
1 other identifier
interventional
14
1 country
1
Brief Summary
Sleep disordered breathing (SDB) is characterized by regular periods of no breathing (apnea) or low levels of breathing (hypopnea) and leads to repeated periods of low oxygenation, termed intermittent hypoxia that causes fluctuations in blood oxygen levels. This leads to increased peripheral chemoreflex sensitivity that is thought to occur through the stimulation of angiotensin-II, type-I receptors (AT1R) that are expressed primarily on glomus cells within the peripheral chemoreflex and ultimately results in long lasting hypertension. The goal of this study is to determine if AT1R receptor blockade can prevent the increase in chemoreflex sensitivity following one night of hypoxia and improve the severity of SDB.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_4
Started Jan 2018
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 1, 2017
CompletedFirst Posted
Study publicly available on registry
November 8, 2017
CompletedStudy Start
First participant enrolled
January 1, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2019
CompletedSeptember 4, 2020
September 1, 2020
1.6 years
November 1, 2017
September 2, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
apnea-hypopnea index
the number of apnea and hypopneas per hour during sleep in hypoxia
8 hours
Secondary Outcomes (6)
Average oxygen saturation
8 hours
Hyperoxic Hypercapnic Ventilatory Response
0 and 8 hours
Hypoxic Hypercapnic Ventilatory Response
0 and 8 hours
Change in systolic and diastolic blood pressure during breath-hold
0 and 8 hours
Hyperoxic Hypercapnic Cerebral Blood Flow Response
0 and 8 hours
- +1 more secondary outcomes
Study Arms (2)
Placebo
PLACEBO COMPARATORParticipants will ingest microcrystalline cellulose by mouth on two consecutive days. The first tablet will be consumed on day 1 at 0700 hrs. The second tablet will be consumed at 1900 hrs and the final tablet will be consumed at 0700hrs on day 2. Participants will undergo a Hyperoxic Hypercapnic Ventilatory Response Test, a Hypoxic Hypercapnic Ventilatory Response Test, and Repeated Hypoxic Apneas before and after a Hypoxic Sleep Study.
Losartan
EXPERIMENTALParticipants will ingest 50 mg of losartan, an angiotensin receptor blocker, by mouth on two consecutive days. The first tablet will be consumed on day 1 at 0700 hrs. The second tablet will be consumed at 1900 hrs and the final tablet will be consumed at 0700hrs on day 2. Participants will undergo a Hyperoxic Hypercapnic Ventilatory Response Test, a Hypoxic Hypercapnic Ventilatory Response Test, and Repeated Hypoxic Apneas before and after a Hypoxic Sleep Study.
Interventions
End-tidal PO2 will be clamped at 300 mmHg while end-tidal PCO2 will be increased in three minutes stages from baseline to +2, +4, and +6 mmHg.
End-tidal PO2 will be clamped at normoxic levels while end-tidal PCO2 will be increased in three minutes stages from baseline to +2, +4, and +6 mmHg.
Six hypoxic apnea cycles will be performed. One apneic cycle involves breathing 2-3 breaths of 100% Nitrogen and breath-holding for 20s followed by room air breathing.
Participants will be instrumented with a sleep monitoring system and will sleep in a normobaric hypoxic chamber with a fraction of inspired oxygen of 13.5%.
Eligibility Criteria
You may qualify if:
- normotensive
- forced expiratory volume in 1s : forced vital capacity ratio \> 0.75
- no medical history of cardiovascular and respiratory disease
- not taking medications other than oral contraceptives
- free from sleep apnea
- body mass index less than 30 kg/m2
You may not qualify if:
- history of hypertension
- known impaired renal function
- liver disease
- heart failure
- myocardial infarction
- coronary artery disease
- smoked within the past year
- apnea hypopnea index \> 5 events per hour
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of British Columbia
Kelowna, British Columbia, V1V 1V7, Canada
Related Publications (1)
Brown CV, Boulet LM, Vermeulen TD, Sands SA, Wilson RJA, Ayas NT, Floras JS, Foster GE. Angiotensin II-Type I Receptor Antagonism Does Not Influence the Chemoreceptor Reflex or Hypoxia-Induced Central Sleep Apnea in Men. Front Neurosci. 2020 Apr 28;14:382. doi: 10.3389/fnins.2020.00382. eCollection 2020.
PMID: 32410951RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Glen Foster, PhD
University of British Columbia
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
November 1, 2017
First Posted
November 8, 2017
Study Start
January 1, 2018
Primary Completion
August 1, 2019
Study Completion
August 1, 2019
Last Updated
September 4, 2020
Record last verified: 2020-09