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Sleep Apnea in Elderly

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ClinicalTrials.gov Identifier: NCT02703220
Recruitment Status : Recruiting
First Posted : March 9, 2016
Last Update Posted : October 17, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

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.

Condition or disease Intervention/treatment Phase
Sleep Apnea Elderly Adults Other: Hyperoxia/oxygen Drug: Acetazolamide Drug: Finasteride Phase 4

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Other
Official Title: Pathophysiology-Guided Therapy for Sleep Apnea in the Elderly
Actual Study Start Date : July 3, 2015
Estimated Primary Completion Date : December 2, 2019
Estimated Study Completion Date : March 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Arm Intervention/treatment
Experimental: Hyperoxia
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.
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

Experimental: Acetazolamide (ACZ)
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.
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.

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




Primary Outcome Measures :
  1. Apneic threshold- a measure of breathing instability [ Time Frame: 2 days to 30 days ]
    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. Cerebrovascular responsiveness to carbon-dioxide [ Time Frame: 7 days ]
    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

  3. Ventilatory responsiveness [ Time Frame: 2 days to 30 days ]
    Hypocapnic ventilatory response; this is calculated as the change in minute ventilation for corresponding changes in PETCO2.

  4. Carbon -dioxide reserve [ Time Frame: 2 days to 30 days ]
    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 :
  1. Apnea hypopnea index [ Time Frame: 2 days to 30 days ]
    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.



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Ages Eligible for Study:   60 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   The Finasteride arm of the study is only applicable for male gender.
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02703220


Contacts
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Contact: Ruchi Rastogi, MSc (313) 576-1000 rrastogi@med.wayne.edu

Locations
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United States, Michigan
John D. Dingell VA Medical Center, Detroit, MI Recruiting
Detroit, Michigan, United States, 48201
Contact: Erin Olgren, PhD MS    313-576-4448    erin.olgren@va.gov   
Principal Investigator: Susmita Chowdhuri, MD         
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Principal Investigator: Susmita Chowdhuri, MD John D. Dingell VA Medical Center, Detroit, MI

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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02703220     History of Changes
Other Study ID Numbers: PULM-008-14F
First Posted: March 9, 2016    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by VA Office of Research and Development:
sleep apnea
chemoresponsiveness
cerebrovascular response
hyperoxia
acetazolamide
finasteride
apneic threshold
carbon-dioxide reserve
Additional relevant MeSH terms:
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Apnea
Sleep Apnea Syndromes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Acetazolamide
Finasteride
Anticonvulsants
Carbonic Anhydrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
5-alpha Reductase Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Urological Agents