Determinants of Age Related Breathing Instability During Non-Rapid-Eye-Movement (NREM) Sleep

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Department of Veterans Affairs
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00732199
First received: August 7, 2008
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

The purpose for our research protocol is to examine the role of breathing control mechanisms that determine the development of sleep-disordered breathing in the elderly. This proposal will focus on key factors that contribute to the control of ventilation in healthy individuals and in subjects with sleep-disordered breathing. We will study the age-specific changes in both normal persons and sleep individuals with sleep apnea.


Condition Intervention
Sleep Apnea
Age
Other: hyperventilation and episodic hypoxia

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Determinants of Age-specific Breathing Instability During Sleep

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Apneic threshold [ Time Frame: 4-6 wks for each participant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Long-term facilitation [ Time Frame: 4-6 wks for each participant ] [ Designated as safety issue: No ]
  • Upper airway resistance [ Time Frame: 4-6 wks for each participant ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: October 2008
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm 1
Young adults, age 18-40 yrs
Other: hyperventilation and episodic hypoxia
noninvasive hyperventilation to determine apneic threshold; episodic hypoxia to determine long term facilitation
Experimental: Arm 2
Older adults, age >40-65yrs
Other: hyperventilation and episodic hypoxia
noninvasive hyperventilation to determine apneic threshold; episodic hypoxia to determine long term facilitation

Detailed Description:

Sleep apnea-hypopnea syndrome (SAS) is a relatively common disorder in the US population with significant adverse health consequences. Despite the high prevalence of SAS in elderly individuals, the underlying mechanisms have remained elusive. Specifically, we do not know whether the high prevalence of sleep apnea in older adults is due to increased central breathing instability. This proposal focuses on investigating age-specific differences in the susceptibility to central breathing instability in healthy individuals as well as individuals with sleep apnea.

This project will investigate the following specific objectives:

  • Determine age-specific changes in the hypocapnic apneic threshold during sleep in

    • elderly vs young individuals without sleep apnea
    • elderly vs young individuals with sleep apnea.
  • Determine age-specific changes in long-term facilitation during sleep in

    • elderly versus young individuals without sleep apnea
    • elderly vs young individuals with sleep apnea.
  • We will investigate the susceptibility to central breathing instability by mechanically ventilating the subjects during NREM sleep using pressure support ventilation. We will compare the hypocapnic apneic threshold in old (age>60-65 years) and young (age 18-40years) individuals who are healthy as well as in those with sleep-disordered breathing. We will also measure the parameters over a continuum of age from 18 to 89y.
  • We will investigate whether there is a difference in the susceptibility to long term facilitation of genioglossus activity and ventilation between young and old healthy individuals in response to episodic hypoxia, while maintaining isocapnia. We will conduct similar experiments in young and old individuals with sleep apnea.

Sleep apnea is very common in older veterans and is associated with significant cardiovascular complications. Greater insight into the pathogenesis will have a positive impact on the health of veterans suffering from this condition. This proposal will further our understanding of the pathogenesis of breathing instability leading to sleep-disordered breathing during sleep. Thus, we anticipate our findings will provide a basis for new approaches to prevention and management of SAS in veterans.

  Eligibility

Ages Eligible for Study:   18 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Normal subjects without sleep apnea (controls) and individuals with sleep apnea.

Exclusion Criteria:

  • Pregnancy,
  • history of active coronary artery disease-including stable and unstable angina,
  • myocardial infarction,
  • history of congestive heart failure,
  • stroke, who have excessive daytime sleepiness with Epworth Sleepiness Scale of >15 will not be included in the study
  • patient with OSA who
  • depression,
  • schizophrenia,
  • untreated hypothyroidism,
  • diabetes on insulin,
  • seizure disorder,
  • intrinsic renal and liver disorders,
  • failure to give informed consent,
  • patients with evidence of pulmonary diseases based on history and abnormal pulmonary function testing, including obstructive (ratio of predicted forced expiratory volume to forced vital capacity, <80% predicted) or restrictive lung disorders (total lung capacity <80% predicted) with resting oxygen saturation of <96% and kyphoscoliosis (chest wall deformities) will be excluded,
  • patients on certain medications including, opiates derivatives, stimulants, antidepressants, tranquilizers, anti-psychotic agents, theophylline and other central nervous system altering medications will be ineligible,
  • history of alcohol or recreational drug use will also serve as grounds for exclusion,
  • patients with body mass index (BMI) >34kg/m2 will be excluded,
  • subjects with sleep apnea are already using continuous positive airway pressure for more than 7 days as therapy will not be eligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00732199

Contacts
Contact: Susmita Chowdhuri, MD (313) 576-1000 ext 63685 schowdh@med.wayne.edu
Contact: Sukanya Pranathiageswaran, MS (313) 576-3548 spranath@med.wayne.edu

Locations
United States, Michigan
John D. Dingell VA Medical Center, Detroit Recruiting
Detroit, Michigan, United States, 48201
Contact: Robert F Molitoris, DDS    313-576-1000 ext 64474    Robert.Molitoris@va.gov   
Principal Investigator: Susmita Chowdhuri, MD         
Sponsors and Collaborators
Investigators
Principal Investigator: Susmita Chowdhuri, MD John D. Dingell VA Medical Center, Detroit
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00732199     History of Changes
Other Study ID Numbers: CDA-2-019-07F
Study First Received: August 7, 2008
Last Updated: March 4, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Sleep apnea syndromes
central apnea
hypoxia
aging

Additional relevant MeSH terms:
Apnea
Sleep Apnea Syndromes
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases

ClinicalTrials.gov processed this record on July 23, 2014