Predictors of Response to Insomnia Treatments for Gulf War Veterans

Status

Completed

Phases

Unknown

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03208049

Enrollment

Registered

2017-07-05

Start date

2017-08-01

Completion date

2023-05-21

Last updated

2026-01-26

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

Conditions

Insomnia

Keywords

Insomnia, Behavioral Therapy, Cognitive Therapy, Sleep, Gulf War Veterans

Brief summary

The purpose of this study is to evaluate the efficacy and effectiveness of Behavioral Therapy (BT) and Cognitive Therapy (CT) in Gulf War Veterans with insomnia. The Primary Outcome measure is the Insomnia Severity Index (ISI).

Detailed description

The investigators' hypotheses will be tested in a randomized parallel groups design. Randomization will be based on type of treatment assignment: either to BT or CT. After screening and randomization in the 2-week baseline phase, subjects will receive BT or CT in the 8-week treatment phase. There will be no more treatment after this point. All subjects will receive education about basic sleep hygiene as well as information about the science of sleep including sleep stages and sleep regulation. Behavioral Therapy (BT). The subject is prescribed a time in bed. After one week, depending on subject's daily sleep logs and adherence to treatment, the therapist suggests a new time in bed prescription. Napping is neither prescribed nor proscribed. However, if subjects find themselves having difficulty staying awake during the day, they are advised to take a brief (15 to 30 minutes) nap to ensure their safety. Subjects in BT are also provided with information about relevant elements of the science of sleep and healthy sleep practices. Cognitive Therapy (CT). CT is designed to meet three general goals: 1) identify dysfunctional sleep cognitions, 2) challenge the validity of these thoughts, and 3) replace them with more adaptive substitutes. Several specific techniques designed to meet these goals are discussed in materials distributed to subjects. The investigators will continue to monitor progress post-treatment during the follow-up period. The complete package of outcome measures will be repeated at the follow-up session. The investigators will tell subjects the expected benefits of treatment is to continue and/or improve with time and the investigators will also encourage subjects to continue practicing the treatment instructions to maintain their progress after active treatment ends. Subjects will be screened for eligibility via a phone interview and an in-person evaluation. At the in-person evaluation, informed consent will be received and documented. The evaluation will consist of measures of cognitive impairment and depression, sleep disturbance, and medical and psychiatric history. The following measures will be completed at weeks 1, 8, and 32: Insomnia Severity Index (ISI), Beck Depression Inventory (BDI); Beck Anxiety Inventory (BAI), 36-Item Short-Form Health Survey (SF-36), Functional Outcomes of Sleep Questionnaire (FOSQ), Multidimensional Fatigue Inventory (MFI), and Wake After Sleep Onset (WASO).

Interventions

BEHAVIORALBehavioral Therapy (BT)

Behavioral Therapy will regulate time spent in bed based on information collected from sleep diaries during evaluation and treatment. Behavioral therapy is designed to improve sleep quality by matching opportunity for sleep to the amount of average total sleep calculated from sleep diaries. Once the quality of sleep has improved, sleep quantity is gradually increased by slowly increasing sleep opportunity. Stimulus control will strengthen the bed/sleep association by eliminating non-sleep activities from the bedroom.

BEHAVIORALCognitive Therapy (CT)

Cognitive Therapy is designed to identify maladaptive beliefs about sleep, challenge their validity, and replace them with more adaptive thinking patterns. This therapy aims to reduce sleep-related worry, anxiety, and fear. The treatment phase of the study lasts six weeks. During treatment, you will meet with a study therapist for a total of six sessions: once per week for six consecutive weeks. Each session lasts approximately 60 minutes.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

The investigators' hypotheses will be tested in a randomized parallel groups design. Randomization will be based on type of treatment assignment: either to Behavioral Therapy (BT) or to Cognitive Therapy (CT). After screening and randomization in the 2-week baseline phase, subjects will receive BT or CT in the 6-week treatment phase. There will be no more treatment after this point. At the end of the 6-week treatment, subjects will return to repeat the tests.

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female Gulf War Veterans of any racial or ethnic group * Independent Living (not in nursing home or VA Extended Care facility) * Subjective complaint of insomnia on the Insomnia Severity Index (ISI) greater than or equal to 10 * Subjects with PTSD will be included in this study as long as they do not meet criteria for depression described below * Stable (3 weeks) CNS active medications that could significantly impact sleep or alertness * Stable adult onset diabetes, controlled with insulin, oral medications or diet is acceptable * Access to a device with video capabilities and ability to have the video on during study visits.

Exclusion criteria

Sleep-Related * Excessive caffeine consumption (4 or more cups of coffee per day) and unable to reduce to 3 cups or less a day before lunch a day for 3 weeks prior to treatment * Subjects will be initially screened by the Berlin Questionnaire (for sleep apnea) * Those with responses suggestive of high risk for sleep apnea will be referred to Pulmonary Medicine for standard clinical screening including polysomnography * Those where apnea is primarily responsible for their sleep complaints will be excluded * Subjects working a rotating shift or an unconventional daytime shift (ending after 1830h) will be ineligible Neuropsychiatric * Hamilton Depression Scale (HDRS 24) and classified as high risk on the Columbia Suicide Severity Rating Scale (C-SSRS) in the past month * Individuals are considered high risk if they have endorsement of either of the following on the C-SSRS: * A positive endorsement, relative to the past 30 days, in the "Suicide Thoughts" section of item #4 (Have you had these thoughts and had some intention of acting on them) or item #5 (Have you started to work out or worked out the details of how to kill yourself? Do you intend to carry out this plan? * A positive endorsement, relative to the past 90 days, in the "Suicide Behavior" section of item #6 (Have you ever done anything, started to do anything, or prepared to do anything to end your life?) * Current or lifetime history of a psychiatric disorder with primary psychotic features * Current or lifetime bipolar disorder; prominent suicidal or homicidal ideation * Current exposure to trauma, or exposure to trauma in the past 3 months * Current or within the past 30 days: drug abuse or dependence (except nicotine) * Current or expected cognitive behavior therapy for another condition (e.g.,: depression) * Excessive alcohol consumption of \>14 drinks per week or \> 4 drinks per occasion * Presence of any acute or unstable psychiatric condition(s) that requires referral for treatment * Montreal Cognitive Assessment (MOCA) \< 20 or Montreal Cognitive Assessment Blind (MOCA-Blind) \< 15 Medical * Acute or unstable chronic illness, including but not limited to: * Uncontrolled thyroid disease * Kidney disease * Prostate or bladder conditions causing excessively frequent urination (\> 3 times per night) * Medically unstable congestive heart failure * Angina * Other severe cardiac illness as defined by treatment regimen changes in the prior 3 months * Stroke with serious sequelae * Cancer if \< 1 year since end of treatment * Asthma * Emphysema * Other severe respiratory diseases uncontrolled with medications * Neurological disorders such as Alzheimer's disease, Parkinson's disease, and/or unstable epilepsy as defined by treatment regimen changes in the prior 3 months * Unstable adult-onset diabetes will be excluded

Design outcomes

Primary

Measure	Time frame	Description
Insomnia Severity Index (ISI)	Week 1, Week 8, and Week 32	Measure Description: This seven-item questionnaire asks respondents to rate the nature and symptoms of their sleep problems using a Likert scale. Questions relate to subjective qualities of sleep, including the severity of symptoms, the satisfaction with sleep patterns, the degree to which insomnia interferes with daily functioning, how noticeable the respondent feels his or her insomnia is to others, and the overall level of distress created by the sleep problem. Responses can range from zero to 4, where higher scores indicate more acute symptoms of insomnia; thus, the total score range is zero to 28.

Secondary

Measure	Time frame	Description
Beck Depression Index (BDI)	Week 1, Week 8, and Week 32	The Beck Depression Index (BDI) is a formative assessment and rating scale of depression. This self-report inventory, or 21-item questionnaire uses a Likert scale that measures the scale quality of magnitude of depression. Responses can range from zero to 3, where higher scores indicate more acute symptoms of depression; thus, the total score range is zero to 63.
Beck Anxiety Index (BAI)	Week 1, Week 8, and Week 32	The Beck Anxiety Index (BAI) is a formative assessment and rating scale of anxiety. This self-report inventory, or 21-item questionnaire uses a Likert scale that measures the scale quality of magnitude of anxiety. Responses can range from zero to 3, where higher scores indicate more acute symptoms of depression; thus, the total score range is zero to 63.
SF 36-Item Health Survey 1.0 (SF-36)	Week 1, Week 8, and Week 32	The 36-Item Short-Form Health Survey (SF-36) is a self-reported patient survey that measures health status and quality of life (QoL). It is used in a variety of settings, including clinical practice, research, and health policy evaluations. To score the SF-36, scales are standardized to obtain a score ranging from 0 to 100. Higher scores indicate better health status,
Functional Outcomes of Sleep Questionnaire (FOSQ)	Week 1, Week 8, and Week 32	The Functional Outcomes of Sleep Questionnaire (FOSQ) is a self-report tool that assesses how sleepiness affects a person's ability to perform daily activities. The score range is 5 to 20, with higher scores indicating better functioning.
Multidimensional Fatigue Inventory (MFI)	Week 1, Week 8, and Week 32	The Multidimensional Fatigue Inventory (MFI), scores each item on a 5-point Likert scale. The total score for each of the five fatigue dimensions (general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue) is calculated by summing the relevant items, resulting in a range of 20 to 100, where a higher score signifies more severe fatigue.
Wake After Sleep Onset (WASO)	Week 1, Week 8, and Week 32	WASO refers to the total amount of time a person spends awake after initially falling asleep and before finally waking up in the morning, essentially measuring the duration of wakefulness periods that occur once sleep has begun; a high WASO indicates fragmented sleep and can be a sign of a sleep disorder like insomnia. WASO will be reported in minutes.

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORJerome A Yesavage, MD

VA Palo Alto Health Care System, Palo Alto, CA

Participant flow

Participants by arm

Arm	Count
Behavioral Therapy (BT) Behavioral Therapy (BT). The subject is prescribed a time in bed. After one week, depending on subject's daily sleep logs and adherence to treatment, the therapist suggests a new time in bed prescription. Napping is neither prescribed nor proscribed. However, if subjects find themselves having difficulty staying awake during the day, they are advised to take a brief (15 to 30 minutes) nap to ensure their safety. Subjects in BT are also provided with information about relevant elements of the science of sleep and healthy sleep practices.	26
Cognitive Therapy (CT) Cognitive Therapy (CT). The CT treatment module is designed to meet three general goals: 1) identify dysfunctional sleep cognitions, 2) challenge their validity, and 3) replace them with more adaptive substitutes. Several specific techniques designed to meet these goals are discussed in materials distributed to subjects. Similar to BT, subjects in CT are provided with information about relevant elements of the science of sleep and healthy sleep practices.	24
Total	50

Baseline characteristics

Characteristic	Behavioral Therapy (BT)	Cognitive Therapy (CT)	Total
Age, Continuous	58.2 years STANDARD_DEVIATION 9.3	54.8 years STANDARD_DEVIATION 6	56.5 years STANDARD_DEVIATION 8
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	3 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants	21 Participants	46 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Insomnia Severity Index (ISI)	17.0 units on a scale STANDARD_DEVIATION 4.4	18.9 units on a scale STANDARD_DEVIATION 3.7	17.9 units on a scale STANDARD_DEVIATION 4.2
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	11 Participants	13 Participants	24 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	4 Participants	6 Participants
Race (NIH/OMB) White	12 Participants	7 Participants	19 Participants
Region of Enrollment United States	26 Participants	24 Participants	50 Participants
Sex: Female, Male Female	5 Participants	5 Participants	10 Participants
Sex: Female, Male Male	21 Participants	19 Participants	40 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 26	0 / 24
other Total, other adverse events	0 / 26	0 / 24
serious Total, serious adverse events	0 / 26	0 / 24

Outcome results

Primary

Insomnia Severity Index (ISI)

Measure Description: This seven-item questionnaire asks respondents to rate the nature and symptoms of their sleep problems using a Likert scale. Questions relate to subjective qualities of sleep, including the severity of symptoms, the satisfaction with sleep patterns, the degree to which insomnia interferes with daily functioning, how noticeable the respondent feels his or her insomnia is to others, and the overall level of distress created by the sleep problem. Responses can range from zero to 4, where higher scores indicate more acute symptoms of insomnia; thus, the total score range is zero to 28.