The purpose of this study is to determine any sleep disordered breathing in veterans with Gulf War Syndrome (GWS) and compare it to healthy normal asymptomatic Gulf War veterans. This study will also determine the effect of treatment with continuous positive airway pressure on veterans with Gulf War Syndrome.
1. The investigators hypothesize that sleep complaints (insomnia, un-refreshing sleep and daytime fatigue) among GWS patients are related to increased sleep fragmentation secondary to the presence of sleep disordered breathing in GWS patients.
2. The investigators hypothesize that increased collapsibility of the upper airway during sleep with the development of inspiratory flow limitation (IFL) and sleep disordered breathing causes the increased sleep fragmentation in GWS patients.
3. The investigators hypothesize that correction of IFL and sleep disordered breathing in GWS patients will result in an improvement of their sleep quality resulting in an improvement of their sleep complaints and other functional symptoms.
Full Title of Study: “Inspiratory Flow Dynamics During Sleep in Gulf War Syndrome (GWS) and the Effect of Continuous Positive Airway Pressure (CPAP)”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Treatment
- Masking: Single (Participant)
- Study Primary Completion Date: October 2008
Hypothesis 1: To demonstrate that compared to Gulf War Veterans without GWS, GWS patients have decreased total sleep and increased sleep fragmentation due to the presence of sleep disordered breathing
In order to accomplish this goal and subsequent goals, we will assemble two samples of Gulf War veterans. The first will be a sample of male GWS patients and the second will be a sample of male Gulf War veterans without GWS (Gulf War veteran control group).
All of the GWS patients will be registered in the Gulf War Veterans Registry. To avoid referral bias favoring the presence of IFL during sleep and sleep disordered breathing, we will enroll GWS patients by contacting them from the Registry and inviting them to participate. Gulf War veteran controls will be recruited in the same way and by advertisement. Prospective study participants will be screened on several self-report instruments to determine eligibility and assignment to the GWS group or to the Gulf War veteran control group.
Criteria for assignment to the GWS group are scores above the designated clinical cutpoint on each of three instruments measuring , fatigue, pain and cognitive dysfunction.
1. Fatigue during the preceding week will be assessed using the fatigue severity scale, a 10-item instrument measuring the level of disability related to fatigue (increasing disability rated 1-7).
2. Pain during the preceding week will be assessed using a pain visual analog scale (VAS; increasing pain rated 0-10 ).
3. Cognitive dysfunction during the preceding week, increasing difficulty with memory, ability to think, and ability to concentrate will be assessed by VAS (increasing cognitive dysfunction rated 0-10 ).
Conversely, criteria for assignment to the GW Veteran control group will require scores in the non-clinical range on each of those instruments. Every subject will have a full night polysomnogram.
Hypothesis 2: To demonstrate that the presence of IFL and sleep disordered breathing during sleep among GWS patients distinguishes them from Gulf War veterans without GWS
A second sleep study will be used to accomplish this second objective. Using precise methods, we will quantify the prevalence of IFL during sleep in GWS patients and in Gulf War veteran controls. Following completion, each study will be staged using Rechtschaffen and Kales criteria. From each study, 3 three minute periods of continuous NREM sleep (a total of approximately 120 breaths) will be randomly selected and analyzed for the prevalence of flow limited breaths. During the three minute periods, all of the breaths will be analyzed whether they occur during sleep or during brief (< 15 second) arousals.
Hypothesis 3: To demonstrate that relief of IFL during sleep and sleep disordered breathing will result in improvement of the functional symptoms of GWS patients
We will accomplish this utilizing a masked parallel group of sham-control and treatment trial of nasal continuous positive airway pressure (CPAP) in GWS patients. Functional symptoms ( fatigue, pain and cognitive dysfunction) will be assessed using validated, self-report questionnaires and daily ratings of symptoms.
- Other: Nasal CPAP treatment during sleep
- After documenting sleep disordered breathing, GWS subject gets randomized to receive either a therapeutic nasal CPAP or a sham nasal CPAP treatment during sleep, GWS symptoms ( fatigue, pain, and cognitive dysfunction) were assessed by a baseline questionnaires and at 3 week period whether on sham or therapeutic CPAP. The change of symptoms in each group will be compared.
Arms, Groups and Cohorts
- Active Comparator: Therapeutic nasal CPAP
- Comparing change of veterans reported outcomes before and after 3 weeks treatment of therapeutic nasal CPAP with the change on sham nasal CPAP.
- Sham Comparator: Sham nasal CPAP
- Comparing change of symptoms and veterans reported outcomes before and after treatment of 3 weeks on sham nasal CPAP with the change on therapeutic nasal CPAP
Clinical Trial Outcome Measures
- Change of Fatigue Symptom
- Time Frame: 3 weeks treatment with either therapeutic or sham CPAP
- Fatigue- increasing impact was rated 1-7 using the fatigue severity scale on days 1 and 7 averaged, where 1= no fatigue and 7= severe fatigue.
- The Prevalence of Inspiratory Flow Limitation (IFL) During Sleep in GWS.
- Time Frame: On a full night polysomnogram
- IFL was determined by plotting inspiratory flow against supra-glottic pressure for each breath sampled during continuous stage 2 sleep on a full night polysomnogram on both veterans with GWS and asymptomatic gulf war veterans. We expressed the prevalence of inspiratory flow limitations during sleep as the percentage of flow limited breath in the sample of both GWS and asymptomatic gulf was veterans.
- Change of Pain Complaint
- Time Frame: 3 weeks of treatment on either therapeutic or sham nasal CPAP
- Pain- increased level were rated 0-10 by visual analogue scale, where 0= no pain and 10= severe pain. We compared the change of pain symptom before and after treatment of either 3 weeks on therapeutic nasal CPAP or sham nasal CPAP
- Change of Cognitive Dysfunction
- Time Frame: 3 weeks treatment with either therapeutic or sham CPAP
- Cognition dysfunction- increasing difficulty with memory, ability to think, and ability to concentrate was rated 0-10 daily by visual analogue scale, where 0 no problem and 10=severe problems.
Participating in This Clinical Trial
- First Gulf War veterans with and without the syndrome
- Between 32 and 52 years of age
- No history of current alcoholism nor opiate use
- No history of current active depression nor post-traumatic stress disorder (PTSD)
- History of active alcoholism or opiate drug use
- History of active depression and PTSD
Gender Eligibility: Male
Minimum Age: 32 Years
Maximum Age: 52 Years
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- US Department of Veterans Affairs
- Provider of Information About this Clinical Study
- Overall Official(s)
- Mohammad Amin, MD, Principal Investigator, VA Medical Center, Northport
Citations Reporting on Results
Amin MM, Gold MS, Broderick JE, Gold AR. The effect of nasal continuous positive airway pressure on the symptoms of Gulf War illness. Sleep Breath. 2011 Sep;15(3):579-87. doi: 10.1007/s11325-010-0406-8. Epub 2010 Aug 19.
Amin MM, Belisova Z, Hossain S, Gold MS, Broderick JE, Gold AR. Inspiratory airflow dynamics during sleep in veterans with Gulf War illness: a controlled study. Sleep Breath. 2011 Sep;15(3):333-9. doi: 10.1007/s11325-010-0386-8. Epub 2010 Aug 12.
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