Respiratory and Autonomic Plasticity Following Intermittent Hypoxia (RAP-IH)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00860743
First received: March 10, 2009
Last updated: September 30, 2013
Last verified: September 2013
  Purpose

The prevalence of obstructive sleep apnea is high in the Veteran population. If not treated promptly, sleep apnea may result in daytime fatigue which may lead to increased prevalence of accidents while driving or in the workplace. Recent large scale epidemiological studies have shown that the prevalence of excessive daytime sleepiness increases in individuals who suffer from obstructive sleep apnea. Obstructive sleep apnea may also result in the development of hypertension and other cardiovascular disorders. Previous findings have shown that subjects with sleep apnea have a greater risk for developing coronary vascular disease compared to individuals that do not suffer from sleep apnea Thus, a significant amount of evidence suggests that sleep apnea is a major health concern in the Veteran population. Consequently, determining the mechanisms that may impact on the severity of sleep apnea and increase the prevalence of cardiovascular incidents associated with this disorder is important, as is discovering novel treatments.


Condition Intervention Phase
Sleep Apnea Syndromes
Drug: Antioxidant cocktail
Phase 0

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Respiratory and Autonomic Plasticity Following Intermittent Hypoxia

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Ventilation [ Time Frame: Within the same experimental session ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Heart Rate Variability [ Time Frame: Within the same experimental session ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
Study Start Date: September 2009
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Arm 1
We plan to study 10 males and 10 females with moderate obstructive sleep apnea (OSA), and 10 healthy males and 10 healthy females. The males and the females will be matched based on age, race, sex and body mass index. The OSA and control participants will be exposed to intermittent hypoxia and "sham" intermittent hypoxia during wakefulness and sleep.
Arm 2
We plan to study 10 male participants with moderate obstructive sleep apnea (OSA) and 10 male control participants matched for age, race and body mass index. The OSA and control participants will be exposed to intermittent hypoxia during wakefulness and sleep following administration of an antioxidant or a placebo cocktail that will be presented in a randomized fashion.
Drug: Antioxidant cocktail
120 mg of Coenzyme Q10 (orally), 800 mg of Superoxide Dismutase (orally), 400 IU of Vitamin E (orally) before exposure to intermittent hypoxia. Two doses of 1 g of Vitamin C in 50 cc of saline IV (in the vein) before and after exposure to intermittent hypoxia.

Detailed Description:

Approximately 8 % of the Veteran population in the United States suffers from sleep apnea. Consequences of untreated sleep apnea include increased daytime fatigue, hypertension and stroke. Thus, sleep apnea is a major health concern. One of the primary hallmarks of sleep apnea is exposure to intermittent hypoxia (IH) which occurs as a consequence of central or obstructive apneas. Exposure to IH may lead to neural plasticity (i.e. a change in system performance based on prior experience) of the respiratory and autonomic nervous system. One adaptation that has been shown to manifest itself in animals following exposure to IH is long-term facilitation (LTF) of ventilation and sympathetic nervous system activity (SNSA). This phenomenon is characterized by a gradual increase in respiratory motor activity and SNSA during successive periods of normoxia that separate hypoxic episodes and by activity that persists above baseline levels for up to 90 minutes following exposure to IH. Although LTF of minute ventilation has been well established in animals it has not been observed consistently in healthy humans or in individuals with obstructive sleep apnea. Similarly, although a few studies have shown that exposure to IH leads to increases in SNSA in healthy individuals the magnitude of the response has varied significantly. Findings from animal studies suggest that the manifestation of LTF in humans might in part be dependent on a variety of factors, including prior exposure to IH, arousal state (wake vs. sleep) and gender. Thus, the initial aim of our proposal will establish whether LTF can be induced in healthy humans and individuals with obstructive sleep apnea and whether the magnitude of the response is dependent on those factors mentioned above. Moreover, the initial aim will explore whether the presence of LTF of minute ventilation promotes or mitigates apnea severity. Animal studies have also indicated that LTF of respiratory and autonomic activity may in part be induced by increases in oxidative stress. Thus, the second objective of our proposal will explore whether administration of an antioxidant cocktail impacts respiratory and autonomic nervous system plasticity during wakefulness and sleep following IH. Likewise, the second aim will explore whether administration of an antioxidant cocktail alters apnea severity following exposure to IH. Establishing whether LTF of minute ventilation exists in individuals with sleep apnea is important since activation of this phenomenon could impact on apnea severity across the night. Similarly, LTF of SNSA activity and possibly long-term depression (LTD) of parasympathetic nervous system activity (PNSA) could ultimately lead to persistent increases in blood pressure and heart rate. Furthermore, given that exposure to IH may lead to long-term plasticity of respiratory and autonomic activity that are physiologically detrimental, exploring mechanisms that ultimately lead to treatments that may mitigate or prevent the manifestation of this phenomenon are important.

  Eligibility

Ages Eligible for Study:   20 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Characteristics of OSA subject population:

  • Body mass index < 30 kg/m2.
  • 20 to 40 years old.
  • Newly diagnosed never-treated mild to moderate sleep apnea (i.e. 50 > apnea/hypopnea index >10 events per hour - average nocturnal oxygen saturation > 90%).
  • Not pregnant.
  • Free of any other known medical conditions.
  • Not taking any medication.
  • Non-smokers with normal lung function.
  • Minimal alcohol consumption (i.e. no more than the equivalent of a glass of wine/day).

Characteristics of control group population:

  • Body mass index < 30 kg/m2.
  • 20 to 40 years old.
  • Apnea/hypopnea index < 5 events per hour.
  • Not pregnant.
  • Free of any known medical conditions.
  • Not taking any medication.
  • Non-smokers with normal lung function.
  • Minimal alcohol consumption (i.e. no more than the equivalent of a glass of wine/day).

Exclusion Criteria:

  • Anything not in inclusion criteria.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00860743

Locations
United States, Michigan
John D. Dingell VA Medical Center, Detroit
Detroit, Michigan, United States, 48201
Sponsors and Collaborators
Investigators
Principal Investigator: Jason H Mateika, PhD John D. Dingell VA Medical Center, Detroit
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00860743     History of Changes
Other Study ID Numbers: PULM-014-08F, GRANT00507547
Study First Received: March 10, 2009
Last Updated: September 30, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
intermittent hypoxia
ventilatory long-term facilitation
autonomic nervous system plasticity

Additional relevant MeSH terms:
Sleep Apnea Syndromes
Anoxia
Apnea
Respiration Disorders
Respiratory Tract Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 23, 2014