Trial Outcomes & Findings for Cognitive Behavioral Therapy for Insomnia for Gulf War Illness (NCT NCT02782780)

NCT ID: NCT02782780

Last Updated: 2021-02-02

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 165 participants
• Primary outcome timeframe: At baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation
• Results posted on: 2021-02-02

Participant Flow

Study participants were recruited from October 2016 to July 2019 by flyers, on-line recruitment, direct mailings to past GW Veteran participants and those on a list provided by the Department of Defense Manpower Data Reporting Center. Of the 165 participants enrolled/consented, 27 did not undergo/complete the clinical assessment interview, 42 were ineligible after the clinical assessment interview, and 11 did not complete baseline assessment. Therefore, only 85 participants were randomized.

During the first phase of screening, veterans participated in a brief telephone interview to inquire about inclusion/exclusion criteria and to determine probable GWI/CMI and insomnia diagnoses. Only participants who passed the initial telephone eligibility screening were invited to undergo a second round of clinical screening to assess for mental health disorders and other exclusionary conditions (e.g., untreated sleep apnea and restless legs syndrome).

Participant milestones

Measure	Monitor Only Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Overall Study STARTED	46	39
Overall Study COMPLETED	39	32
Overall Study NOT COMPLETED	7	7

Reasons for withdrawal

Measure	Monitor Only Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Overall Study dropped out after randomization.	7	5
Overall Study Protocol Violation	0	2

Baseline Characteristics

Cognitive Behavioral Therapy for Insomnia for Gulf War Illness

Baseline characteristics by cohort

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.	Total n=85 Participants Total of all reporting groups
Age, Continuous	54 years STANDARD_DEVIATION 6 • n=5 Participants	55 years STANDARD_DEVIATION 7 • n=7 Participants	54.1 years STANDARD_DEVIATION 6.3 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	28 Participants n=7 Participants	64 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	25 Participants n=7 Participants	61 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	46 Participants n=5 Participants	39 Participants n=7 Participants	85 Participants n=5 Participants

PRIMARY outcome

Timeframe: At baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: 32 of 39 participants randomized to CBTi completed treatment; only 28 of these participants completed the 6-month follow-up assessment.

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.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Gulf War Illness Symptom Severity Index Baseline	67 score on a scale Interval 53.0 to 78.0	67 score on a scale Interval 58.0 to 82.0
Gulf War Illness Symptom Severity Index Post-treatment	61 score on a scale Interval 50.0 to 78.0	49 score on a scale Interval 44.0 to 62.0
Gulf War Illness Symptom Severity Index 6-month follow-up	—	54 score on a scale Interval 49.0 to 66.0

PRIMARY outcome

Timeframe: At baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: 32 of 39 participants randomized to CBTi completed treatment; only 28 of these participants completed the 6-month follow-up assessment.

The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia in the last month. The dimensions evaluated are: severity of sleep onset, sleep maintenance, and early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by the sleep difficulties. A 5-point Likert scale is used to rate each item (e.g., 0 = no problem; 4 = very severe problem), yielding a total score ranging from 0 to 28. Higher scores indicate more severe insomnia. This outcome will be measured at 8 weeks in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Insomnia Severity Index (ISI) post-treatment	19.0 score on a scale Interval 13.5 to 22.0	10.0 score on a scale Interval 6.0 to 15.0
Insomnia Severity Index (ISI) 6-month follow-up	—	13.0 score on a scale Interval 7.0 to 18.0
Insomnia Severity Index (ISI) Baseline	19.0 score on a scale Interval 16.0 to 24.0	21.0 score on a scale Interval 18.0 to 24.0

SECONDARY outcome

Timeframe: Baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: 32 of 39 participants randomized to CBTi completed treatment; only 28 of these participants completed the 6-month follow-up assessment.

The FSS is a 9-item questionnaire reflecting the consequences of fatigue. It gives a single score (range 0-7, high scores represent high levels of fatigue). A score of 4 has been described as the cutoff for clinical fatigue. This outcome will be measured at baseline, after 8 weeks in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Fatigue Severity Scale (FSS) Baseline	5.06 score on a scale Interval 3.47 to 5.78	5.56 score on a scale Interval 4.67 to 6.28
Fatigue Severity Scale (FSS) Post-treatment	5.11 score on a scale Interval 3.22 to 5.83	3.44 score on a scale Interval 2.89 to 5.03
Fatigue Severity Scale (FSS) 6-month follow-up	—	3.67 score on a scale Interval 2.78 to 5.44

SECONDARY outcome

Timeframe: Baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: 32 of 39 participants randomized to CBTi completed treatment; only 28 of these participants completed the 6-month follow-up assessment.

The BPI is a 17-item self-rating scale assessing demographic data, use of medications, as well as sensory, and reactive components of pain. The BPI measures two domains: pain intensity (severity) and the impact of pain on functioning (interference). The score range for BPI-Severity is 0-10, higher score = more severe/intense pain. The range for BPI-interference is 0-10, higher score = greater impact of pain on function.

This outcome will be measured at baseline, after 8 weeks in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Brief Pain Inventory (BPI) - Pain Interference Baseline	4.29 score on a scale Interval 2.46 to 6.68	5.86 score on a scale Interval 3.79 to 7.29
Brief Pain Inventory (BPI) - Pain Interference Post-treatment	4.57 score on a scale Interval 2.07 to 6.86	4.29 score on a scale Interval 1.57 to 5.57
Brief Pain Inventory (BPI) - Pain Interference 6-month follow-up	—	4.29 score on a scale Interval 1.64 to 6.64

SECONDARY outcome

Timeframe: Baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: 32 of 39 participants randomized to CBTi completed treatment; only 28 of these participants completed the 6-month follow-up assessment.

The BPI is a 17-item self-rating scale assessing demographic data, use of medications, as well as sensory, and reactive components of pain. The BPI measures two domains: pain intensity (severity) and the impact of pain on functioning (interference). The score range for BPI-Severity is 0-10, higher score = more severe/intense pain. The range for BPI-interference is 0-10, higher score = greater impact of pain on function. This outcome will be measured at baseline, after 8 weeks in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Brief Pain Inventory (BPI) - Pain Severity Baseline	4.12 score on a scale Interval 2.88 to 6.75	5.00 score on a scale Interval 3.38 to 6.5
Brief Pain Inventory (BPI) - Pain Severity Post-treatment	4.25 score on a scale Interval 2.88 to 5.75	5.25 score on a scale Interval 3.0 to 5.75
Brief Pain Inventory (BPI) - Pain Severity 6-month follow-up	—	5.00 score on a scale Interval 3.0 to 6.0

SECONDARY outcome

Timeframe: Baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: 32 of 39 participants randomized to CBTi completed treatment; only 28 of these participants completed the 6-month follow-up assessment.

The MASQ is a 38-item self-report measure of cognitive function compared to same age peers across 5 domains (i.e., verbal memory, attention, language, visual memory, visuo-perceptual ability). Score range: 38-190. Higher scores = greater cognitive dysfunction.

This outcome will be measured at baseline, after 8 weeks in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Multiple Abilities Self-Report Questionnaire (MASQ) Baseline	64 score on a scale Interval 39.0 to 77.0	61 score on a scale Interval 44.0 to 76.0
Multiple Abilities Self-Report Questionnaire (MASQ) Post-treatment	68 score on a scale Interval 42.0 to 89.0	55 score on a scale Interval 37.0 to 69.0
Multiple Abilities Self-Report Questionnaire (MASQ) 6-month followup	—	54 score on a scale Interval 44.0 to 77.0

SECONDARY outcome

Timeframe: Baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: 32 of 39 participants randomized to CBTi completed treatment; only 28 of these participants completed the 6-month follow-up assessment.

The HADS will be used to assess anxiety and depressive symptoms. The HADS is widely used in community settings and in primary care and not just in "hospitals." The range for HADS-anxiety measure is 0-21. Higher scores = more anxiety.

This outcome will be measured at baseline, after 8 weeks in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Hospital Anxiety and Depression Scale (HADS), Anxiety Baseline	10.5 score on a scale Interval 6.2 to 13.8	12.5 score on a scale Interval 9.2 to 14.0
Hospital Anxiety and Depression Scale (HADS), Anxiety Post-treatment	11.0 score on a scale Interval 7.0 to 15.5	8.0 score on a scale Interval 5.0 to 11.0
Hospital Anxiety and Depression Scale (HADS), Anxiety 6-month follow-up	—	9.0 score on a scale Interval 6.5 to 11.0

SECONDARY outcome

Timeframe: Baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: Only 28 participants completed the 6-month assessments.

The HADS will be used to assess anxiety and depressive symptoms. The HADS is widely used in community settings and in primary care and not just in "hospitals." The range for HADS-depression measure is 0-21. Higher scores = more anxiety.

This outcome will be measured at baseline, after 8 weeks in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Hospital Anxiety and Depression Scale (HADS), Depression Baseline	9.0 score on a scale Interval 5.2 to 11.8	9.5 score on a scale Interval 7.0 to 12.0
Hospital Anxiety and Depression Scale (HADS), Depression Post-treatment	9.0 score on a scale Interval 5.5 to 11.0	4.0 score on a scale Interval 2.0 to 8.0
Hospital Anxiety and Depression Scale (HADS), Depression 6-month follow-up	—	6.0 score on a scale Interval 3.0 to 9.0

SECONDARY outcome

Timeframe: Baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: Only 28 of the participants randomized to CBTi completed the 6-month follow-up assessment.

The PSQI is a self-report measure that provides a subjective assessment of sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sedative-hypnotics, and daytime energy. This index is widely used and has been validated by polysomnography. The score range for the PSQI is 0 to 21, with the higher scores indicating worse sleep quality.This outcome will be measured at baseline, after 8 weeks in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Pittsburgh Sleep Quality Index (PSQI) Baseline	12.0 score on a scale Interval 9.2 to 14.8	11.0 score on a scale Interval 9.0 to 15.0
Pittsburgh Sleep Quality Index (PSQI) Post-treatment	11.0 score on a scale Interval 8.5 to 13.0	8.0 score on a scale Interval 3.0 to 9.0
Pittsburgh Sleep Quality Index (PSQI) 6-month follow-up	—	7.0 score on a scale Interval 5.0 to 10.5

SECONDARY outcome

Timeframe: Baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: Only 28 of the participants randomized to CBTi completed the 6-month assessment.

Sleep Efficiency, as determined by self-reported sleep diary, is the total sleep time (TST) divided by the time in bed, multiplied by 100. Good sleepers have high sleep efficiency because they are asleep the majority of time they spend in bed. Insomniacs tend to have low sleep efficiency because they spend a lot of time awake while they are in bed (tossing and turning).

This outcome will be measured at baseline, after 8 weeks in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Sleep Efficiency (SE) Baseline	82 percent Interval 74.0 to 89.0	83 percent Interval 74.0 to 88.0
Sleep Efficiency (SE) Post-treatment	78 percent Interval 73.0 to 89.0	94 percent Interval 90.0 to 95.0
Sleep Efficiency (SE) 6-month follow-up	—	91 percent Interval 89.0 to 94.0

SECONDARY outcome

Timeframe: Baseline and after 8 weeks of study participation in all subjects; in subjects randomized to CBTi, 6 months after study participation

Population: Only 28 of the participants randomized to CBTi completed the 6-month follow-up assessment.

Wake After Sleep Onset is the amount of time that a person is awake time during the night, as recorded in a self-report sleep diary. Insomniacs tend to have greater WASO than good sleepers because they wake up a lot in the middle of the might.

This outcome will be measured at baseline, post-treatment in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Minutes of Wake After Sleep Onset (WASO) Baseline	25 minutes Interval 11.0 to 43.0	31 minutes Interval 19.0 to 53.0
Minutes of Wake After Sleep Onset (WASO) Post-treatment	33 minutes Interval 18.0 to 57.0	7 minutes Interval 4.0 to 22.0
Minutes of Wake After Sleep Onset (WASO) 6-month follow-up	—	20 minutes Interval 11.0 to 27.0

SECONDARY outcome

Timeframe: Baseline, after 8 weeks of study participation in all subjects, in subjects randomized to CBTi, 6 months after study participation

Population: Only 28 participants randomized to CBTi completed the 6-month follow-up.

Sleep latency (SL) is the amount of time that it takes someone to fall asleep. Participants will be asked to estimate this time in their sleep diaries. Good sleepers tend to have low sleep latencies because they can fall asleep quickly. Insomniacs tend to have longer sleep latencies because it takes them a long time to fall asleep.

This outcome will be measured at baseline, after 8 weeks in both the CBTi and monitor-only groups and at 6 months in subjects randomized to CBTi.

Outcome measures

Measure	Monitor Only n=46 Participants Study participants who are randomized to the Monitor Only (MO) control group will be followed for 8 weeks of usual care (i.e., they will be advised to continue doing whatever they were doing to manage their GWI and insomnia symptoms without change dosage or frequency of treatment). Participants randomized to the Monitor Only condition will have the option of receiving CBTi delivered by telephone, at no cost to them, upon completion of post-study procedures.	CBTi n=39 Participants CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep as well as to work with the patient toward altering sleep habits to increase sleep propensity and regularity. Specifically, participants will receive 8 weekly individual sessions of CBTi according to the VA CBTi protocol. The investigators will follow the semi-structured approach to treatment described in the VA CBTi protocol, which allows the case conceptualization to drive the order in which treatment components are introduced. Cognitive Behavioral Therapy for Insomnia (CBTi): CBTi is a multicomponent treatment that seeks to teach patients about sleep and the factors that affect sleep (e.g., homeostatic regulation, circadian rhythm, age, social and work schedule) and to work with the patients toward minimizing unwanted arousal at bedtime and altering sleep habits to increase sleep propensity and regularity. The intervention is 8-weeks long.
Sleep Latency (SL) Baseline	22 minutes Interval 15.0 to 44.0	22 minutes Interval 13.0 to 34.0
Sleep Latency (SL) Post-treatment	24 minutes Interval 14.0 to 46.0	10 minutes Interval 7.0 to 12.0
Sleep Latency (SL) 6-month follow-up	—	12 minutes Interval 7.0 to 16.0

Adverse Events

Monitor Only

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

CBTi

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Linda Chao

San Francisco VA Health Care System

Phone: 415-221-4810

Email: linda.chao@va.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place