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Sleep Disordered Breathing in Gulf War Illness and the Effect of Nasal CPAP Treatment

Inspiratory Flow Dynamics During Sleep in Gulf War Syndrome (GWS) and the Effect of Continuous Positive Airway Pressure (CPAP)

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00252629
Enrollment
29
Registered
2005-11-11
Start date
2005-11-30
Completion date
2010-11-30
Last updated
2014-12-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Apnea, Sleep, Chronic Fatigue Syndrome

Keywords

Fatigue, Functional Somatic Syndrome, Gulf War Syndrome, Sleep apnea, Upper Airway Resistance Syndrome

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.

Interventions

OTHERNasal 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.

Sponsors

US Department of Veterans Affairs
Lead SponsorFED

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)

Eligibility

Sex/Gender
MALE
Age
32 Years to 52 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Change of Fatigue Symptom3 weeks treatment with either therapeutic or sham CPAPFatigue- 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.On a full night polysomnogramIFL 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.

Secondary

MeasureTime frameDescription
Change of Pain Complaint3 weeks of treatment on either therapeutic or sham nasal CPAPPain- 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 Dysfunction3 weeks treatment with either therapeutic or sham CPAPCognition 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.

Countries

United States

Participant flow

Recruitment details

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.

Participants by arm

ArmCount
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.
9
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.
9
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
11
Total29

Baseline characteristics

CharacteristicTherapeutic Nasal CPAPSham Nasal CPAPHealthy Asymptomatic ControlTotal
Age, Continuous41.4 years
STANDARD_DEVIATION 4.1
42.9 years
STANDARD_DEVIATION 3.1
41 years
STANDARD_DEVIATION 6.6
42.2 years
STANDARD_DEVIATION 0.7
Sex: Female, Male
Female
0 Participants0 Participants0 Participants0 Participants
Sex: Female, Male
Male
9 Participants9 Participants11 Participants29 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
0 / 90 / 90 / 11
serious
Total, serious adverse events
0 / 90 / 90 / 11

Outcome results

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.

Time frame: 3 weeks treatment with either therapeutic or sham CPAP

ArmMeasureValue (MEAN)Dispersion
Therapeutic Nasal CPAPChange of Fatigue Symptom2.1 units on a scaleStandard Error 0.9
Sham Nasal CPAPChange of Fatigue Symptom0.2 units on a scaleStandard Error 1
Comparison: The change of fatigue complaint from baseline (before treatment) to post treatment ( after 3 weeks treatment) on either therapeutic CPAP or sham CPAP was compared with student t-test.p-value: 0.0002t-test, 2 sided
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.

Time frame: On a full night polysomnogram

ArmMeasureValue (MEAN)Dispersion
Therapeutic Nasal CPAPThe Prevalence of Inspiratory Flow Limitation (IFL) During Sleep in GWS.96 percentage of flow limited breathsStandard Deviation 5
Sham Nasal CPAPThe Prevalence of Inspiratory Flow Limitation (IFL) During Sleep in GWS.36 percentage of flow limited breathsStandard Deviation 25
Comparison: The p value was based on t-testp-value: 0.0001t-test, 2 sided
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.

Time frame: 3 weeks treatment with either therapeutic or sham CPAP

ArmMeasureValue (MEAN)Dispersion
Therapeutic Nasal CPAPChange of Cognitive Dysfunction2.0 units on a scaleStandard Deviation 1.7
Sham Nasal CPAPChange of Cognitive Dysfunction0.4 units on a scaleStandard Deviation 1
Comparison: The change of cognitive dysfunction complaint from baseline (before treatment) to post treatment ( after 3 weeks treatment) on either therapeutic CPAP or sham CPAP was compared with student t-test.p-value: 0.004t-test, 2 sided
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

Time frame: 3 weeks of treatment on either therapeutic or sham nasal CPAP

ArmMeasureValue (MEAN)Dispersion
Therapeutic Nasal CPAPChange of Pain Complaint2.0 units on a scaleStandard Deviation 0.9
Sham Nasal CPAPChange of Pain Complaint0.4 units on a scaleStandard Deviation 1.2
Comparison: The change of pain symptom from baseline (before treatment) to post treatment ( after 3 weeks treatment) on either therapeutic CPAP or sham CPAP was compared with student t-test.p-value: 0.0008t-test, 2 sided

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026