Clinical trial NCT03208049: Predictors of Response to Insomnia Treatments for Gulf War Veterans
Official title: Predictors of Response to Insomnia Treatments for Gulf War Veterans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insomnia
Keywords: Insomnia
Behavioral Therapy
Cognitive Therapy
Sleep
Gulf War Veterans
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2017-07-05
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Insomnia Severity Index (ISI)
timeFrame: Week 1, Week 8, and Week 32
Secondary outcomes:
measure: Beck Depression Index (BDI)
timeFrame: Week 1, Week 8, and Week 32
measure: Beck Anxiety Index (BAI)
timeFrame: Week 1, Week 8, and Week 32
measure: SF 36-Item Health Survey 1.0 (SF-36)
timeFrame: Week 1, Week 8, and Week 32
measure: Functional Outcomes of Sleep Questionnaire (FOSQ)
timeFrame: Week 1, Week 8, and Week 32
measure: Multidimensional Fatigue Inventory (MFI)
timeFrame: Week 1, Week 8, and Week 32
measure: Wake After Sleep Onset (WASO)
timeFrame: Week 1, Week 8, and Week 32
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: VA Palo Alto Health Care System, Palo Alto, CA
state: California
city: Washington
country: United States
facility: Washington DC VA Medical Center, Washington, DC
state: District of Columbia
city: East Orange
country: United States
facility: East Orange Campus of the VA New Jersey Health Care System, East Orange, NJ
state: New Jersey
Study officials:
affiliation: VA Palo Alto Health Care System, Palo Alto, CA
name: Jerome A Yesavage, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tao Y, Peters ME, Drye LT, Devanand DP, Mintzer JE, Pollock BG, Porsteinsson AP, Rosenberg PB, Schneider LS, Shade DM, Weintraub D, Yesavage J, Lyketsos CG, Munro CA. Sex Differences in the Neuropsychiatric Symptoms of Patients With Alzheimer's Disease. Am J Alzheimers Dis Other Demen. 2018 Nov;33(7):450-457. doi: 10.1177/1533317518783278. Epub 2018 Jul 3.
citation: Yesavage JA, Fairchild JK, Mi Z, Biswas K, Davis-Karim A, Phibbs CS, Forman SD, Thase M, Williams LM, Etkin A, O'Hara R, Georgette G, Beale T, Huang GD, Noda A, George MS; VA Cooperative Studies Program Study Team. Effect of Repetitive Transcranial Magnetic Stimulation on Treatment-Resistant Major Depression in US Veterans: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Sep 1;75(9):884-893. doi: 10.1001/jamapsychiatry.2018.1483.
citation: McNerney MW, Sheng T, Nechvatal JM, Lee AG, Lyons DM, Soman S, Liao CP, O'Hara R, Hallmayer J, Taylor J, Ashford JW, Yesavage J, Adamson MM. Integration of neural and epigenetic contributions to posttraumatic stress symptoms: The role of hippocampal volume and glucocorticoid receptor gene methylation. PLoS One. 2018 Feb 7;13(2):e0192222. doi: 10.1371/journal.pone.0192222. eCollection 2018.
citation: Hantke N, Adamson MM, Noda A, Lazzeroni LC, Beaudreau SA, Yutsis M, Fairchild JK, Kinoshita LM, Kong J, Sheng T, Waltzman D, Ashford JW, Yesavage JA. Posttraumatic Stress Disorder-Associated Cognitive Deficits on the Repeatable Battery for the Assessment of Neuropsychological Status in a Veteran Population. Fed Pract. 2021 Jan;38(1):28-34. doi: 10.12788/fp.0083.