Sleep-disordered breathing (SDB or sleep apnea) is very common among elderly Veterans and leads to increased morbidity and mortality in this population. The proposal aims to identity whether oxygen, finasteride and acetazolamide can be effective in reducing unstable breathing and eliminating sleep apnea in the elderly via different mechanisms. This proposal will enhance the investigators' understanding of the pathways that contribute to the development of sleep apnea in the elderly. The investigators expect that the results obtained from this study will positively impact the health of Veterans by identifying new treatment modalities for sleep apnea. A cumulative effect of the investigators' research will fulfill the long-term goal of improving the quality of life of elderly Veterans suffering from sleep apnea and its potential life-threatening complications.
Sleep apnea-hypopnea syndrome (SAHS) has a high prevalence and is associated with adverse cardiovascular consequences in elderly Veterans. Positive airway pressure therapy is deemed cumbersome and often associated with non-adherence to therapy. This proposal will investigate whether alternative therapies can be developed by modulating specific physiologic mechanisms of ventilatory control. Specifically, the investigators will study whether interventions with sustained hyperoxia (Aim 1), finasteride (Aim 2) and acetazolamide (Aim 3) will reduce breathing instability during sleep by reducing chemoresponsiveness and/or increasing cerebrovascular reactivity (CVR) in order to alleviate sleep disordered breathing in the elderly with sleep apnea. The proposed aims will also allow us to delineate key mechanisms of breathing instability in the elderly. The investigators envision that the results obtained from this project will ultimately allow us to develop novel alternative therapies for sleep apnea in the elderly. We will also compare CVR in young vs older adults
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
100
The ventilatory effects of brief hyperoxia will be assessed by analyzing control breaths on room air immediately preceding the hyperoxic exposure, and comparing with the primary end-point, nadir minute ventilation breath, immediately following the brief hyperoxic exposure
Participants with sleep apnea will ingest capsules containing either placebo or acetazolamide 500 mg twice a day for 5 days. On the final 2 consecutive nights while still on ACZ, the investigators will perform i) physiology tests and ii) in-lab follow-up PSG.
Elderly males with sleep apnea and adequate testosterone levels will ingest placebo vs finasteride, at 5 mg a day for 1 month (mo). After 1 mo, while still on the drug, on the final 2 consecutive nights, the investigators will perform i) physiology tests and ii) in-lab follow-up PSG. Blood tests will be performed to check sex hormone levels. A washout period of 1 month prior to cross-over to the alternate arm (placebo).
John D. Dingell VA Medical Center, Detroit, MI
Detroit, Michigan, United States
RECRUITINGApneic threshold- a measure of breathing instability
Measures of breathing instability including: Apneic threshold: this is the end-tidal Co2 at which a central apnea closes to a hypopnea is produced.
Time frame: 2 days to 30 days
Cerebrovascular responsiveness to carbon-dioxide
Cerebrovascular response to different levels of CO2: this is a measure of the response of the cerebral blood flow to changes in carbon dioxide levels and is used as a measure of ventilatory control of breathing
Time frame: 7 days
Ventilatory responsiveness
Hypocapnic ventilatory response; this is calculated as the change in minute ventilation for corresponding changes in PETCO2.
Time frame: 2 days to 30 days
Carbon -dioxide reserve
This is a derived measure. This is calculated as the difference between the apneic threshold PETCO2 (given above) and the control PETCO2.
Time frame: 2 days to 30 days
Apnea hypopnea index
Apnea hypopnea index- is a measure of severity of sleep apnea - this is calculated as the total number of apneas and hypopneas recorded during a sleep study divided by the total sleep time during the sleep study.
Time frame: 2 days to 30 days
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