Sleep Apnea in Elderly

Sleep Apnea Clinical Trial

Official title:

Pathophysiology-Guided Therapy for Sleep Apnea in the Elderly

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02703220
• Other study ID #: PULM-008-14F
• Status: Recruiting
• Phase: Phase 4
• Start date: July 3, 2015
• Est. completion date: June 30, 2024

Study information

• Verified date: August 2023
• Source: VA Office of Research and Development
• Contact: Ruchi Rastogi, MSc
• Phone: (313) 576-1000
• Email: ruchi.rastogi[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years to 89 Years

Eligibility

Inclusion Criteria:

• Adults who are 60 years old and older, with mild to moderate sleep apnea with AHI >/=5 to 20/hr with central, obstructive, mixed apneas and hypopneas.

• For the finasteride protocol elderly men with above criteria will be enrolled.

Exclusion Criteria:

• Patients with severe sleep apnea (AHI>20/hr)

• Patients with history of prostate cancer

• Males with hypogonadism

• History of cardiac disease, including myocardial infarction

• Bypass surgery

• Atrial and ventricular tachy-bradycardias

• Systolic congestive heart failure and Cheyne-Stokes respiration

• Current unstable angina

• Stroke

• Schizophrenia

• Untreated hypothyroidism

• Seizure disorder

• Preexisting renal failure and liver disorders

• Failure to give informed consent.

• Patients with significant pulmonary diseases by history and abnormal pulmonary function testing, including moderate obstructive/restrictive lung/chest wall disorders with resting oxygen saturation of <96% or on supplemental oxygen

• Patients on certain medications including:

• study drugs

• sympathomimetics/parasympathomimetics or their respective blockers

• narcotics

• antidepressants

• anti-psychotic agents

• other central nervous system (CNS) altering medications

• current alcohol, tobacco or recreational drug use

• Patients with BMI>34kg/m2 will be excluded to avoid the effects of morbid obesity on pulmonary mechanics and ventilatory control

• Elderly with unstable gait or mobility issues that may preclude safe participation

• Individuals with allergy to finasteride or acetazolamide will be excluded from the specific protocol

• Pregnant women

Related Conditions & MeSH terms

• Apnea
• Elderly Adults
• Sleep Apnea
• Sleep Apnea Syndromes

Intervention

Other:
• Hyperoxia/oxygen
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

Drug:
• Acetazolamide
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.
• Finasteride
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).

Locations

Country	Name	City	State
United States	John D. Dingell VA Medical Center, Detroit, MI	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (1)

Rastogi R, Badr MS, Ahmed A, Chowdhuri S. Amelioration of sleep-disordered breathing with supplemental oxygen in older adults. J Appl Physiol (1985). 2020 Dec 1;129(6):1441-1450. doi: 10.1152/japplphysiol.00253.2020. Epub 2020 Sep 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Apneic 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.	2 days to 30 days
Primary	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	7 days
Primary	Ventilatory responsiveness	Hypocapnic ventilatory response; this is calculated as the change in minute ventilation for corresponding changes in PETCO2.	2 days to 30 days
Primary	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.	2 days to 30 days
Secondary	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.	2 days to 30 days