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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.
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Therapeutic nasal CPAP | Active Comparator | Comparing change of veterans reported outcomes before and after 3 weeks treatment of therapeutic nasal CPAP with the change on sham nasal CPAP. |
|
| Sham nasal CPAP | Sham Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nasal CPAP treatment during sleep | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change of Fatigue Symptom | 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. | 3 weeks treatment with either therapeutic or sham CPAP |
| The Prevalence of Inspiratory Flow Limitation (IFL) During Sleep in GWS. | 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. | On a full night polysomnogram |
| Measure | Description | Time Frame |
|---|---|---|
| Change of Pain Complaint | 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 | 3 weeks of treatment on either therapeutic or sham nasal CPAP |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mohammad Amin, MD | VA Medical Center, Northport | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Medical Center, Northport | Northport | New York | 11768 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20717848 | Result | 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. | |
| 20703820 | Result | 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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18 male veterans with GWI and Sleep Disordered Breathing recruited by advertisement, they were splitter into a matched two groups: 9 veterans received active nasal CPAP and 9 veterans received sham nasal CPAP.
Additionally, we recruited asymptomatic 11 male veterans of Gulf war.
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| ID | Title | Description |
|---|---|---|
| FG000 | Therapeutic Nasal CPAP | Nine participants assigned to receive 3 weeks of treatment during sleep with therapeutic nasal CPAP. Using validated questionnaires, fatigue, pain, and cognitive dysfunction were assessed by self-report before and after the three weeks treatment trial. We compared the change of veterans reported outcomes "symptoms change" before and after 3 weeks treatment period on therapeutic nasal CPAP. |
| FG001 | Sham Nasal CPAP | Nine participants assigned to receive 3 weeks of treatment during sleep with sham nasal CPAP. Using validated questionnaires, fatigue, pain, and cognitive dysfunction were assessed by self-report before and after the three weeks treatment trial. We compared the change of veterans reported outcomes "symptoms change" before and after 3 weeks treatment period on sham nasal CPAP. |
| FG002 | Comparison of IFL During Sleep in GWS and Healthy | We recruited 18 male veterans with GWS (same group that were randomized to receive CPAP treatment) and 11 asymptomatic male veterans of the first Gulf war. All veterans had a polysomnography to determine the presence of sleep disordered breathing. We compared the prevalence of Inspiratory Flow Limitation (IFL) during supine stage 2 sleep among both groups. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Therapeutic Nasal CPAP | The occurrence of the following 3 symptoms in a Gulf War veteran beginning after 8/90, lasting at least 6 months and present at the time of screening: fatigue that limits usual activity; musculoskeletal pain involving 2 or more regions of the body; and cognitive symptoms (memory, concentration, or attention difficulties). All 3 symptoms must be unexplained by any clearly defined organic illness. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change of Fatigue Symptom | 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. | Posted | Mean | Standard Error | units on a scale | 3 weeks treatment with either therapeutic or sham CPAP |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Therapeutic Nasal CPAP | Comparing change of veterans reported outcomes ( fatigue, pain and cognitive dysfunction) before and after 3 weeks treatment on therapeutic nasal CPAP with change of symptoms on sham nasal CPAP |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mohammad M. Amin, MD | Northport, VAMC | 6312614400 | 2469 | mohammad.amin2@va.gov |
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| ID | Term |
|---|---|
| D012891 | Sleep Apnea Syndromes |
| D015673 | Fatigue Syndrome, Chronic |
| D005221 | Fatigue |
| D018923 | Persian Gulf Syndrome |
| ID | Term |
|---|---|
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
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|
| Change of Cognitive Dysfunction |
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. |
| 3 weeks treatment with either therapeutic or sham CPAP |
| BG001 | Sham Nasal CPAP | The occurrence of the following 3 symptoms in a Gulf War veteran beginning after 8/90, lasting at least 6 months and present at the time of screening: fatigue that limits usual activity; musculoskeletal pain involving 2 or more regions of the body; and cognitive symptoms (memory, concentration, or attention difficulties). All 3 symptoms must be unexplained by any clearly defined organic illness. |
| BG002 | Healthy Asymptomatic Control | Eleven male veterans of first gulf war were screened for fatigue, pain and cognitive dysfunction by self report instrument. They all score below the clinical thershold and assigned as healthy asymptomatic |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Secondary | Change of Pain Complaint | 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 | Posted | Mean | Standard Deviation | units on a scale | 3 weeks of treatment on either therapeutic or sham nasal CPAP |
|
|
|
|
| Secondary | Change of Cognitive Dysfunction | 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. | Posted | Mean | Standard Deviation | units on a scale | 3 weeks treatment with either therapeutic or sham CPAP |
|
|
|
|
| Primary | The Prevalence of Inspiratory Flow Limitation (IFL) During Sleep in GWS. | 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. | Posted | Mean | Standard Deviation | percentage of flow limited breaths | On a full night polysomnogram |
|
|
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | Sham Nasal CPAP | Comparing change of veterans reported outcomes ( fatigue, pain and cognitive dysfunction) before and after 3 weeks treatment on sham nasal CPAP with change of symptoms on therapeutic nasal CPAP | 0 | 9 | 0 | 9 |
| EG002 | Comparison of IFL During Sleep in GWS and Healthy | We recruited 11 asymptomatic male veterans of the first Gulf war. In addition to our 18 male veterans with GWS (same group that were randomized to receive CPAP treatment). All veterans had a polysomnography to determine the presence of sleep disordered breathing. We compared the prevalence of Inspiratory Flow Limitation (IFL) during supine stage 2 sleep among both groups. | 0 | 11 | 0 | 11 |
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| D020920 |
| Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D004679 | Encephalomyelitis |
| D000090862 | Neuroinflammatory Diseases |
| D009468 | Neuromuscular Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D009784 | Occupational Diseases |
| D000067398 | War-Related Injuries |
| D014947 | Wounds and Injuries |