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Sleep Apnea in Elderly

Primary Purpose

Sleep Apnea, Elderly Adults

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Hyperoxia/oxygen

Acetazolamide

Finasteride

About this trial

This is an interventional other trial for Sleep Apnea focused on measuring sleep apnea, chemoresponsiveness, cerebrovascular response, hyperoxia, acetazolamide, finasteride, apneic threshold, carbon-dioxide reserve

Eligibility Criteria

60 Years - 89 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

John D. Dingell VA Medical Center, Detroit, MIRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Hyperoxia

Acetazolamide (ACZ)

Finasteride

Arm Description

Determine the effect of sustained hyperoxia overnight vs room air overnight on ventilatory control during sleep, including the apneic threshold, carbon-dioxide reserve and chemosensitivity measured via pressure support ventilation (PSV) during (non-rapid eye movement sleep) NREM sleep.

Determine the effect of acetazolamide on cerebrovascular responsiveness to CO2 during wake and sleep. Participants will receive oral ACZ therapy for 7 days prior to the experimental night, on the night of the study and the subsequent night when polysomnography (PSG) will be performed.

Determine the effect of oral finasteride therapy vs placebo for 1 month on SDB and the AT and chemosensitivity during NREM sleep.

Outcomes

Primary Outcome Measures

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.

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

Ventilatory responsiveness

Hypocapnic ventilatory response; this is calculated as the change in minute ventilation for corresponding changes in PETCO2.

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02703220

First Posted

January 29, 2016

Last Updated

August 16, 2023

Sponsor

VA Office of Research and Development

1. Study Identification

Unique Protocol Identification Number

NCT02703220

Brief Title

Sleep Apnea in Elderly

Official Title

Pathophysiology-Guided Therapy for Sleep Apnea in the Elderly

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 3, 2015 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

VA Office of Research and Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sleep Apnea, Elderly Adults

Keywords

sleep apnea, chemoresponsiveness, cerebrovascular response, hyperoxia, acetazolamide, finasteride, apneic threshold, carbon-dioxide reserve

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

Participant

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Hyperoxia

Arm Type

Experimental

Arm Description

Arm Title

Acetazolamide (ACZ)

Arm Type

Experimental

Arm Description

Arm Title

Finasteride

Arm Type

Experimental

Arm Description

Determine the effect of oral finasteride therapy vs placebo for 1 month on SDB and the AT and chemosensitivity during NREM sleep.

Intervention Type

Other

Intervention Name(s)

Hyperoxia/oxygen

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Acetazolamide

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Finasteride

Intervention Description

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).

Primary Outcome Measure Information:

Title

Apneic threshold- a measure of breathing instability

Description

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

Title

Cerebrovascular responsiveness to carbon-dioxide

Description

Time Frame

7 days

Title

Ventilatory responsiveness

Description

Hypocapnic ventilatory response; this is calculated as the change in minute ventilation for corresponding changes in PETCO2.

Time Frame

2 days to 30 days

Title

Carbon -dioxide reserve

Description

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

Secondary Outcome Measure Information:

Title

Apnea hypopnea index

Description

Time Frame

2 days to 30 days

10. Eligibility

Sex

All

Gender Based

Yes

Gender Eligibility Description

The Finasteride arm of the study is only applicable for male gender.

Minimum Age & Unit of Time

60 Years

Maximum Age & Unit of Time

89 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ruchi Rastogi, MSc

Phone

(313) 576-1000

ruchi.rastogi@va.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Susmita Chowdhuri, MD

Organizational Affiliation

John D. Dingell VA Medical Center, Detroit, MI

Official's Role

Principal Investigator

Facility Information:

Facility Name

John D. Dingell VA Medical Center, Detroit, MI

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201-1916

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Edi Levi, MD

Phone

313-576-4451

edi.levi@va.gov

First Name & Middle Initial & Last Name & Degree

Susmita Chowdhuri, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32969781

Citation

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.

Results Reference

result

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Sleep Apnea in Elderly

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