Pilot Test of Apnea and Insomnia Relief for Veterans With Gulf War Illness

Gulf War Illness Clinical Trial

— GWAIR  

Official title:

Pilot Test of Apnea and Insomnia Relief for Veterans With Gulf War Illness

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05137743
• Other study ID #: 21-33521
• Status: Recruiting
• Phase: N/A
• Start date: February 15, 2022
• Est. completion date: June 30, 2026

Study information

• Verified date: November 2023
• Source: University of California, San Francisco
• Contact: Alyssa Indrajaya, BA
• Phone: 415-630-0273
• Email: alyssa.indrajaya[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether a behavioral sleep treatment improves sleep and other Gulf War Illness (GWI) symptoms in Gulf War Veterans with GWI.

Description:

This study is a randomized controlled trial of a behavioral sleep treatment to improve sleep and other symptoms of Gulf War Illness (GWI) in Gulf War (GW) Veterans with GWI, sleep apnea, and insomnia. The treatment is delivered via telehealth (video to home) or telephone. The primary outcome for this study is the severity of Gulf War Illness symptom severity. Other outcomes include sleep-related functioning, insomnia symptom severity, and positive airway pressure (PAP) adherence.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 30, 2026
• Est. primary completion date: February 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 48 Years to 80 Years

Eligibility

Inclusion Criteria:

• Male and female GW Veterans between the ages of 48-80

• Deployed to the "Gulf Theater of operations," as defined by 38 CFR 3.317

• Meets the Kansas GWI and Centers for Disease Control and Prevention (CDC) Chronic Multisymptom Illness (CMI) case definitions. The Kansas GWI definition requires cases to endorse multiple or moderate-to-severe chronic symptoms in at least three of six symptom domains. These include: i) fatigue/sleep problems, ii) somatic pain, iii) neurological cognitive, mood symptoms, iv) gastrointestinal symptoms, v) respiratory symptoms, and vi) skin abnormalities. Veterans will be excluded from being considered Kansas GWI cases, for purposes of the proposed trial, if they report being diagnosed by a physician with medical or psychiatric conditions that would account for their symptoms or interfere with their ability to report their symptoms. Veterans with current or past history of PTSD or depression in the past 5 years will not be excluded from participation if they have not been hospitalized for these conditions. The CDC CMI case definition requires cases to endorse symptoms in at least two of three symptom clusters. These include: i) fatigability (e.g., feeling fatigue for 24 hours or more after exertion), ii) mood/cognitive symptoms (e.g., feeling depressed, irritable, worried, tense or anxious; difficulty thinking or concentrating, problems finding words, or problems getting to or staying asleep). iii) musculoskeletal pain.

• Meet the DSM-5 research diagnostic criteria for insomnia disorder. Unlike other GWI symptoms, we will not require the Veteran's insomnia to have begun during the Gulf War or within one year after leaving the Gulf region. This is because some GWI symptoms may cause veterans to adopt behaviors that lead to sleep problems later. Results from our CBT-I trial in Veterans with GWI suggest that improving sleep also improves non-sleep related symptoms such as fatigue, depression, pain, and psychosocial function. Therefore, we hypothesize that even if insomnia was not one of the original GWI symptoms, improving sleep in veterans with GWI will also improve other GWI-related symptoms.

• Diagnosed with obstructive sleep apnea (OSA) by physician based on polysomnography or evidence of OSA based on an Apnea-Hyponea Index (AHI) or respiratory disturbance index (RDI) that is > or = 5 based on home sleep apnea testing.

• Have access to wireless internet connection at home for remote positive airway pressure (PAP) data capture.

Exclusion Criteria:

• Condition(s) that is/are considered exclusionary for the Kansas GWI criteria. For purposes of this trial, this will include medical or psychiatric conditions diagnosed by a physician/psychiatrist that would account for the Veterans' symptoms or interfere with their ability to report their symptoms. Specific exclusionary criteria include medical conditions such as uncontrolled diabetes, heart disease other than hypertension, stroke, lupus, multiple sclerosis, cancer, liver disease, chronic infection, or serious neurological condition (e.g., dementia, brain injury).

• History of any psychiatric disorder with active psychosis or mania in the past 5 years.

• Severe drug or alcohol use disorder within the past 6 months as assessed by the Structured Clinical Interview for DSM-5 (SCID 5). Veterans with moderate drug or alcohol use disorder will be reviewed on a case-by-case basis.

• Prominent suicidal or homicidal ideation.

• Pregnancy, because insomnia will worsen after 8 weeks.

• Restless Legs Syndrome (RLS) or screening indicative of RLS based on Restless legs syndrome screening questionnaire (RLSSQ).

• Current enrollment in another clinical trial.

• Traumatic brain injury (TBI) will not be exclusionary for the proposed study unless it impacts cognition to a degree that the Veteran cannot complete treatment or homework assignments (this will be determined on a case-by-case basis at PI and therapists' discretion).

• Starting or ending psychotherapy for a sleep disorder or mental health diagnosis within the last one month.

• Starting or ending an antidepressant, anxiolytic, or sleep medication with the last one month will be excluded. Veterans currently receiving benzodiazepine or benzodiazepine receptor agonists, anticonvulsants, atypical antipsychotic medication, or non-SSRI antidepressant medications such as trazodone will be not be excluded provided that they meet the DSM-5 criteria for insomnia disorder, exhibit evidence of OSA, and will remain on the medication(s) throughout the 6-week treatment period and the 3-month follow-up period.

Related Conditions & MeSH terms

• Gulf War Illness
• Sleep Initiation and Maintenance Disorders

Intervention

Behavioral:
• Apnea and Insomnia Relief (AIR)
This treatment will be offered over six sessions. All appointments will be conducted via telehealth and will last 60 minutes. The main components of the AIR protocol are (a) psychoeducation, (b) motivational interviewing, (c) PAP adherence strategies, and (d) cognitive behavioral therapy for insomnia.
• Sleep Education (SE)
This treatment will be offered over six sessions. All appointments will be conducted via telehealth and will last 60 minutes. Topics covered include the sleep cycle, sleep across the lifespan, sleep and the mind, evening activities and the sleep environment, and daytime activities and sleep.

Locations

Country	Name	City	State
United States	VA Health Care System	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	San Francisco VA Health Care System, United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (1)

Chao LL, Kanady JC, Crocker N, Straus LD, Hlavin J, Metzler TJ, Maguen S, Neylan TC. Cognitive behavioral therapy for insomnia in veterans with gulf war illness: Results from a randomized controlled trial. Life Sci. 2021 Aug 15;279:119147. doi: 10.1016/j.lfs.2021.119147. Epub 2021 Feb 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Gulf War Illness Symptom Severity Index	Due to its novelty, complexity, and variability, no single measure of severity addresses all possible presentations of Gulf War Illness (GWI). Therefore, we used the symptom portion of the Kansas Gulf War Military History and Health Questionnaire to query about fatigue/sleep problems, somatic pain, skin abnormalities, gastrointestinal, respiratory, and neurologic/cognitive/mood symptoms, based on the Kansas GWI and CDC CMI case definition. To assess current GWI symptoms, participants will be asked about the absence (0), presence, and severity (1=mild; 2=moderate; 3=severe) of the symptoms over the past 2 weeks instead of over the past 6-months. Score range: 0-87; higher scores = more symptoms and/or more severe symptoms.	Change from baseline to 1 week post-treatment (after 6 weeks).
Primary	Change in Gulf War Illness Symptom Severity Index	Due to its novelty, complexity, and variability, no single measure of severity addresses all possible presentations of Gulf War Illness (GWI). Therefore, we used the symptom portion of the Kansas Gulf War Military History and Health Questionnaire to query about fatigue/sleep problems, somatic pain, skin abnormalities, gastrointestinal, respiratory, and neurologic/cognitive/mood symptoms, based on the Kansas GWI and CDC CMI case definition. To assess current GWI symptoms, participants will be asked about the absence (0), presence, and severity (1=mild; 2=moderate; 3=severe) of the symptoms over the past 2 weeks instead of over the past 6-months. Score range: 0-87; higher scores = more symptoms and/or more severe symptoms.	Change from baseline to 3 months after treatment ends.
Primary	Change in Positive Airway Pressure (PAP) Adherence	PAP adherence will be measured via PAP device data capture. The average hours of PAP use will be measured from session 1 through post-treatment.	Change from baseline to 1 week post-treatment (after 6 weeks).
Primary	Positive Airway Pressure (PAP) Adherence	PAP adherence will be measured via PAP device data capture. The average hours of PAP use will be measured for 1 week at the follow-up 3 months after treatment ends.	Change from baseline to 3 months after treatment ends.
Secondary	Insomnia Severity Index (ISI)	This seven-item self-report scale assesses severity of insomnia. Responses to items range from 0 to 4. Total scores range from 0 to 28. Higher scores indicate greater symptom severity.	Change from baseline to 1 week post-treatment (after 6 weeks).
Secondary	Insomnia Severity Index (ISI)	This seven-item self-report scale assesses severity of insomnia. Responses to items range from 0 to 4. Total scores range from 0 to 28. Higher scores indicate greater symptom severity.	Change from baseline to 3 months after treatment ends.