Predictors of Response to Insomnia Treatments for Gulf War Veterans
| Status: | Recruiting |
|---|---|
| Conditions: | Insomnia Sleep Studies |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 20 - Any |
| Updated: | 12/2/2018 |
| Start Date: | August 1, 2017 |
| End Date: | July 31, 2021 |
| Contact: | Andrea Goldstein, PhD |
| Email: | Andrea.Goldstein2@va.gov |
| Phone: | (650) 493-5000 |
The purpose of this study is to evaluate the efficacy and effectiveness of sleep restriction
(SR) and cognitive therapy (CT) in Gulf War Veterans with insomnia.
The primary hypothesis is that the efficacy of these treatments will depend upon an
individual subject's baseline characteristics. For SR we expect that baseline measures of
"excessive time spent in bed" may predict response and for CT we expect that baseline
measures of cognitive arousal and pain may predict response. Exploratory analyses using
signal detection techniques will systematically compare and contrast the potential usefulness
of a number of additional potential moderator measures.
Insomnia is a serious health problem in Gulf War Veterans that is often associated with
extensive prescription of sleeping medications. Although safer, even the latest "sleeping
pills" can lead to cognitive impairment and risk of abuse. Thus non-pharmacological
treatments for insomnia have been pursued as alternatives to medications. Cognitive Behavior
Therapy for Insomnia (CBT-I) is the term widely used to describe therapies that combine
behavioral and cognitive therapies for insomnia. The combined CBT-I approach has
well-documented efficacy. Between 2012 and 2014 over 650 VA mental health clinicians have
received extensive training in CBT-I. Although CBT-I is efficacious, the optimal target
populations for its major components has not yet been well-defined for Gulf War Veterans. We
propose to address this gap and develop tools for clinicians to identify the best treatment
for insomnia for individual Gulf War Veterans.
(SR) and cognitive therapy (CT) in Gulf War Veterans with insomnia.
The primary hypothesis is that the efficacy of these treatments will depend upon an
individual subject's baseline characteristics. For SR we expect that baseline measures of
"excessive time spent in bed" may predict response and for CT we expect that baseline
measures of cognitive arousal and pain may predict response. Exploratory analyses using
signal detection techniques will systematically compare and contrast the potential usefulness
of a number of additional potential moderator measures.
Insomnia is a serious health problem in Gulf War Veterans that is often associated with
extensive prescription of sleeping medications. Although safer, even the latest "sleeping
pills" can lead to cognitive impairment and risk of abuse. Thus non-pharmacological
treatments for insomnia have been pursued as alternatives to medications. Cognitive Behavior
Therapy for Insomnia (CBT-I) is the term widely used to describe therapies that combine
behavioral and cognitive therapies for insomnia. The combined CBT-I approach has
well-documented efficacy. Between 2012 and 2014 over 650 VA mental health clinicians have
received extensive training in CBT-I. Although CBT-I is efficacious, the optimal target
populations for its major components has not yet been well-defined for Gulf War Veterans. We
propose to address this gap and develop tools for clinicians to identify the best treatment
for insomnia for individual Gulf War Veterans.
Our hypotheses will be tested in a randomized parallel groups design. Randomization will be
based on type of treatment assignment: either to SR or CT. After screening and randomization
in the 2-week baseline phase, subjects will receive SR 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 many of the psychological tests administered during baseline
to determine the short-term benefit. This 4-year proposal will include 100 subjects (2 groups
of 50 each) with outcome, mediator and moderator measures collected at appropriate points.
All subjects will receive education about basic sleep hygiene as well as information about
the science of sleep including sleep stages and sleep regulation.
Sleep Restriction Therapy (SR). The initial Time in Bed (TIB) prescription is calculated on
the average total sleep time (TST) reported in the baseline sleep logs. After one week,
depending on subject's daily sleep logs, the therapist suggests a new TIB prescription.
Napping is neither prescribed nor proscribed. However, if subjects find themselves very
sleepy (not just tired, but actually sleepy) they are advised to take a brief (15 to 30
minutes) nap to ensure their safety.
Cognitive Therapy (CT). The CT treatment module is designed to meet three general goals: 1)
identification of dysfunctional sleep cognitions, 2) challenging their validity, and 3)
replacing them with more adaptive substitutes. Several specific techniques designed to meet
these goals are discussed in materials distributed to subjects. Similar to SR, subjects in CT
are given information about relevant elements of the science of sleep and healthy sleep
practices.
We will also continue to monitor progress post-treatment in the follow-up period. The
complete package of outcome measures will be repeated at the follow-up session. We will tell
subjects that we expect the benefits of treatment to continue and/or improve with time and we
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, after signing a consent form, a more detailed interview about
sleep problems, and medical and psychiatric history will be obtained by the Duke Structured
Sleep Interview, including evaluations of cognitive impairment and depression. Exclusion
criteria will further be evaluated by the following given solely at the office evaluation:
Acute/Unstable Chronic Illness checklist, Berlin Questionnaire, Columbia Suicide Severity
Rating Scale (C-SSRS), DUKE Structured Sleep Interview, Hamilton Depression Rating Scale
(HDRS24), Life Stressor Checklist, Mini International Neuropsychiatric Interview Version 5
(MINI), Montreal Cognitive Assessment (MOCA), Morningness-Eveningness Questionnaire, Sleep
Related Behavior Questionnaire, and the Thought Control Questionnaire Insomnia-Revised
(TCQI). Subjects will additionally be set up with PSG equipment. The PSG will be completed in
the subject's own home and be used to screen for Obstructive Sleep Apnea and Periodic Limb
Movement Disorder. Subjects will return to the lab the next morning to have the equipment
removed.
Participants will be evaluated on the Anxiety and Preoccupation about Sleep Questionnaire
(APSQ), Depression Anxiety and Stress Scale (DASS-21), Epworth Sleepiness Scale, and the
Insomnia Severity Index each visit during weeks 1-8, and again at week 32. Sleep logs will be
done daily during weeks 1-8, and again at week 32. The following will be done at weeks 1, 8,
and 32:
AUA8 Noctoria; Brief Pain Inventory short form (BPI-SF); Beck Anxiety Inventory (BAI); Beck
Depression Inventory (BDI); Clinician Administered PTSD Scale (CAPS); Dysfunctional Beliefs
and Attitudes about Sleep Scale; AUA8 (DBAS); Glasgow Content of Thoughts; Glasgow Sleep
Effort Scale; Multidimensional fatigue Inventory; Penn State Worry Questionnaire (PSWQ);
Perceived Stress Scale (PSS); SF-36 (RAND).
Subjects will be evaluated on Functional Outcomes of Sleep Questionnaire at weeks 1, 2, 8 and
32.
Subjects will be evaluated on the SAMI at weeks 1 and 8.
Subjects will be evaluated on the Trial Making Test, MOCA, Color Word Interference test and
the RBANS at weeks 1 and 32.
Following the completion of treatment at week 7, subjects will complete the Treatment
Adherence Survey, Treatment Satisfaction Survey and Working Alliance Inventory. The Working
Alliance Inventory will also be given at the second treatment session (week 3).
Blood will be drawn to measure levels of C-reactive protein (CRP). Urine samples will be
collected at during each of the 3 study phases to monitor abstain from drugs of abuse, except
for medical marijuana used less than four times a week. Samples will be collected by nurses
at the VA Clinical Studies Unit and analyzed by the VA lab. Blood samples will be taken at
the same time to be analyzed for C-reactive protein. Remaining blood will be banked to be
analyzed for genetic factors.
based on type of treatment assignment: either to SR or CT. After screening and randomization
in the 2-week baseline phase, subjects will receive SR 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 many of the psychological tests administered during baseline
to determine the short-term benefit. This 4-year proposal will include 100 subjects (2 groups
of 50 each) with outcome, mediator and moderator measures collected at appropriate points.
All subjects will receive education about basic sleep hygiene as well as information about
the science of sleep including sleep stages and sleep regulation.
Sleep Restriction Therapy (SR). The initial Time in Bed (TIB) prescription is calculated on
the average total sleep time (TST) reported in the baseline sleep logs. After one week,
depending on subject's daily sleep logs, the therapist suggests a new TIB prescription.
Napping is neither prescribed nor proscribed. However, if subjects find themselves very
sleepy (not just tired, but actually sleepy) they are advised to take a brief (15 to 30
minutes) nap to ensure their safety.
Cognitive Therapy (CT). The CT treatment module is designed to meet three general goals: 1)
identification of dysfunctional sleep cognitions, 2) challenging their validity, and 3)
replacing them with more adaptive substitutes. Several specific techniques designed to meet
these goals are discussed in materials distributed to subjects. Similar to SR, subjects in CT
are given information about relevant elements of the science of sleep and healthy sleep
practices.
We will also continue to monitor progress post-treatment in the follow-up period. The
complete package of outcome measures will be repeated at the follow-up session. We will tell
subjects that we expect the benefits of treatment to continue and/or improve with time and we
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, after signing a consent form, a more detailed interview about
sleep problems, and medical and psychiatric history will be obtained by the Duke Structured
Sleep Interview, including evaluations of cognitive impairment and depression. Exclusion
criteria will further be evaluated by the following given solely at the office evaluation:
Acute/Unstable Chronic Illness checklist, Berlin Questionnaire, Columbia Suicide Severity
Rating Scale (C-SSRS), DUKE Structured Sleep Interview, Hamilton Depression Rating Scale
(HDRS24), Life Stressor Checklist, Mini International Neuropsychiatric Interview Version 5
(MINI), Montreal Cognitive Assessment (MOCA), Morningness-Eveningness Questionnaire, Sleep
Related Behavior Questionnaire, and the Thought Control Questionnaire Insomnia-Revised
(TCQI). Subjects will additionally be set up with PSG equipment. The PSG will be completed in
the subject's own home and be used to screen for Obstructive Sleep Apnea and Periodic Limb
Movement Disorder. Subjects will return to the lab the next morning to have the equipment
removed.
Participants will be evaluated on the Anxiety and Preoccupation about Sleep Questionnaire
(APSQ), Depression Anxiety and Stress Scale (DASS-21), Epworth Sleepiness Scale, and the
Insomnia Severity Index each visit during weeks 1-8, and again at week 32. Sleep logs will be
done daily during weeks 1-8, and again at week 32. The following will be done at weeks 1, 8,
and 32:
AUA8 Noctoria; Brief Pain Inventory short form (BPI-SF); Beck Anxiety Inventory (BAI); Beck
Depression Inventory (BDI); Clinician Administered PTSD Scale (CAPS); Dysfunctional Beliefs
and Attitudes about Sleep Scale; AUA8 (DBAS); Glasgow Content of Thoughts; Glasgow Sleep
Effort Scale; Multidimensional fatigue Inventory; Penn State Worry Questionnaire (PSWQ);
Perceived Stress Scale (PSS); SF-36 (RAND).
Subjects will be evaluated on Functional Outcomes of Sleep Questionnaire at weeks 1, 2, 8 and
32.
Subjects will be evaluated on the SAMI at weeks 1 and 8.
Subjects will be evaluated on the Trial Making Test, MOCA, Color Word Interference test and
the RBANS at weeks 1 and 32.
Following the completion of treatment at week 7, subjects will complete the Treatment
Adherence Survey, Treatment Satisfaction Survey and Working Alliance Inventory. The Working
Alliance Inventory will also be given at the second treatment session (week 3).
Blood will be drawn to measure levels of C-reactive protein (CRP). Urine samples will be
collected at during each of the 3 study phases to monitor abstain from drugs of abuse, except
for medical marijuana used less than four times a week. Samples will be collected by nurses
at the VA Clinical Studies Unit and analyzed by the VA lab. Blood samples will be taken at
the same time to be analyzed for C-reactive protein. Remaining blood will be banked to be
analyzed for genetic factors.
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 to10
- 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
Exclusion Criteria:
Sleep-Related
- Excessive caffeine consumption (4 cups of coffee per day) and unable to reduce to 3
cups 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 in which apnea is primarily responsible for their sleep complaints should
be excluded
- Subjects working a rotating shift or an unconventional daytime shift (ending after
1830 h will be ineligible
Neuropsychiatric
- Hamilton Depression Scale (HDRS 24) and classified as high risk on the Columbia
Suicide Severity Scale (past month)
- Individuals are considered high risk if they have endorsement of either of the
following:
- 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
- >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
Medical
- Acute or unstable chronic illness, including but not limited to:
- uncontrolled thyroid disease
- kidney
- 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
- or other severe respiratory diseases uncontrolled with medications
- neurological disorders such as Alzheimer's disease, Parkinson's disease and
unstable epilepsy as defined by treatment regimen changes in the prior 3 months
- Unstable adult onset diabetes will be excluded
We found this trial at
1
site
Palo Alto, California 94304
Principal Investigator: Jerome A Yesavage, MD
Phone: 650-493-5000
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