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

Chronic Fatigue Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00252629
• Other study ID #: RCD-001-05S
• Status: Completed
• Phase: N/A
• First received: November 9, 2005
• Last updated: December 10, 2014
• Start date: November 2005
• Est. completion date: November 2010

Study information

• Verified date: December 2014
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: November 2010
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 32 Years to 52 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Apnea, Sleep
• Chronic Fatigue Syndrome
• Fatigue Syndrome, Chronic
• Sleep Apnea Syndromes
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
United States	VA Medical Center, Northport	Northport	New York

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	3 weeks treatment with either therapeutic or sham CPAP	No
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.	On a full night polysomnogram	No
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	3 weeks of treatment on either therapeutic or sham nasal CPAP	No
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.	3 weeks treatment with either therapeutic or sham CPAP	No