AT1R Blockade and Periodic Breathing During Sleep in Hypoxia

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.

Conditions

• Sleep Disordered Breathing
• Hypoxia
• Respiration; Sleep Disorder
• Chemoreceptor Apnea

Interventions

OTHER

Hyperoxic Hypercapnic Ventilatory Response Test

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.

OTHER

Hypoxic Hypercapnic Ventilatory Response Test

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.

OTHER

Repeated Hypoxic Apneas

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.

OTHER

Hypoxic Sleep Study

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%.

DRUG

Losartan

Losartan, 50mg, BID

DRUG

Placebo

Placebo, 50mg, BID

Sponsors & Collaborators

• University of British Columbia

  lead OTHER

Principal Investigators

• Glen Foster, PhD · University of British Columbia

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-01-01

Primary Completion

2019-08-01

Completion

2019-08-01

Countries

• Canada

Study Locations