- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00860743
Respiratory and Autonomic Plasticity Following Intermittent Hypoxia (RAP-IH)
September 29, 2017 updated by: VA Office of Research and Development
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
63
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Michigan
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Detroit, Michigan, United States, 48201
- John D. Dingell VA Medical Center, Detroit
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years to 40 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
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Experimental: ANTIOXIDANT COCKTAIL
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.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ventilation (Aim 1)
Time Frame: Within the same experimental session
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Ventilation was measured before and after exposure to intermittent hypoxia in males and females.
Ventilation was measured using a pneumotachograph, which is a flow measuring device.
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Within the same experimental session
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Heart Rate Variability (Aim 2)
Time Frame: Within the same experimental session
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Heart rate variability (HRV) was measured before and after exposure to intermittent hypoxia following administration of a placebo or antioxidant cocktail.
Heart rate variability refers to beat-to-beat alterations in heart rate.
Under resting conditions, the electrocardiogram of healthy individuals reveals periodic variation in R-R intervals.
To measure HRV, R-R interval data are presented in a graph, in which the y-axis plots the R-R intervals (ms2), and the x-axis the total number of beats.
Spectral analysis of the graph transforms the signal from time to frequency on the x-axis (Hz), by representing the signal as a combination of sine and cosine waves, with different amplitudes and frequencies.
The approach uses Fourier transforms.
The heart rate spectrum contains a high frequency (0.15-0.4 Hz) component, which is synchronous with respiration and a low frequency (0.04 to 0.15 Hz) component that appears to be mediated by both the vagus and cardiac sympathetic nerves.
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Within the same experimental session
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Jason H Mateika, PhD MS BS, John D. Dingell VA Medical Center, Detroit
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Mateika JH, Syed Z. Intermittent hypoxia, respiratory plasticity and sleep apnea in humans: present knowledge and future investigations. Respir Physiol Neurobiol. 2013 Sep 15;188(3):289-300. doi: 10.1016/j.resp.2013.04.010. Epub 2013 Apr 12.
- Syed Z, Lin HS, Mateika JH. The impact of arousal state, sex, and sleep apnea on the magnitude of progressive augmentation and ventilatory long-term facilitation. J Appl Physiol (1985). 2013 Jan 1;114(1):52-65. doi: 10.1152/japplphysiol.00985.2012. Epub 2012 Nov 8.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2009
Primary Completion (Actual)
September 1, 2013
Study Completion (Actual)
September 1, 2013
Study Registration Dates
First Submitted
March 10, 2009
First Submitted That Met QC Criteria
March 10, 2009
First Posted (Estimate)
March 12, 2009
Study Record Updates
Last Update Posted (Actual)
November 1, 2017
Last Update Submitted That Met QC Criteria
September 29, 2017
Last Verified
September 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Nervous System Diseases
- Respiratory Tract Diseases
- Apnea
- Respiration Disorders
- Sleep Disorders, Intrinsic
- Dyssomnias
- Sleep Wake Disorders
- Signs and Symptoms, Respiratory
- Sleep Apnea Syndromes
- Hypoxia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Protective Agents
- Antioxidants
Other Study ID Numbers
- PULM-014-08F
- GRANT00507547 (Other Grant/Funding Number: VA Merit)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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