Clinical trial NCT00252629: Sleep Disordered Breathing in Gulf War Illness and the Effect of Nasal CPAP Treatment
Official title: Inspiratory Flow Dynamics During Sleep in Gulf War Syndrome (GWS) and the Effect of Continuous Positive Airway Pressure (CPAP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Apnea, Sleep
Chronic Fatigue Syndrome
Keywords: Fatigue
Functional Somatic Syndrome
Gulf War Syndrome
Sleep apnea
Upper Airway Resistance Syndrome
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2005-11-11
Enrollment: 29
Sex: MALE
Minimum age (years): 32
Maximum age (years): 52
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* First Gulf War veterans with and without the syndrome
* Males
* 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)

Exclusion Criteria:

* Females
* History of active alcoholism or opiate drug use
* History of active depression and PTSD

Primary outcomes:
measure: Change of Fatigue Symptom
timeFrame: 3 weeks treatment with either therapeutic or sham CPAP
measure: The Prevalence of Inspiratory Flow Limitation (IFL) During Sleep in GWS.
timeFrame: On a full night polysomnogram
Secondary outcomes:
measure: Change of Pain Complaint
timeFrame: 3 weeks of treatment on either therapeutic or sham nasal CPAP
measure: Change of Cognitive Dysfunction
timeFrame: 3 weeks treatment with either therapeutic or sham CPAP
Other outcomes:
Locations:
city: Northport
country: United States
facility: VA Medical Center, Northport
state: New York
Study officials:
affiliation: VA Medical Center, Northport
name: Mohammad Amin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.