The Efficacy of CBT-I in Alcoholics & Its Effects on Remission & Relapse
Phase: NA
Conditions: Insomnia
Sponsor: VA Office of Research and Development

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CMCVAMC Specific Protocol Summary
Content Requirements for IRB Committee Review
CMCVAMC IRB
Corporal Michael Crescenz VA Medical Center Institutional
Review Board
A.
Protocol Title
1
Full Protocol Title: The Efficacy of CBT-I in Alcoholics & Its Effects on Remission & Relapse
2.
Date of Protocol Summary and Version #: Date August 21, 2018 Version #8.
B.
Principal Investigator's Full Name and Degree: Subhajit Chakravorty,
C.
Co-Investigator's Full Name and Degree:
N/A
Approved by CMCVAMC IRB 2
8/22/2018
D.
Financial Sponsor (Provide the name of the agency, organization, company or person providinq
funds for the research study.)
VA CSR&D
E.
Grant (Provide the name of individual who holds the grant and the grant number
if applicable )
Subhajit Chakravorty, MD; 1 IK2CX000855-01A2
F.
Protocol Number (Provide the financial sponsor's protocol number,
if applicable.)
N/A
NoD
G.
Institution(s) responsible for the project:
1.
For single-site studies - CMCVAMC is the only institution involved.
Yes
2.
For multi-center studies.
2.1.
CMCVAMC is the Coordinating Center in which the PI is the lead investigator.
Yes Q
No
□
N/A £3
2.2.
Provide the name of the Coordinating Center.
Yes D
No D
N/A ^
2.3.
List the name of the other sites involved.
N/A
2.4.
Provide the FWA numbers for each of the other sites involved.
N/A
H.
Background and Significance:
Alcohol dependence (alcoholism) and insomnia
in Veterans occur at rates that are 2-7 times higher
than that of the general population. Further, there is evidence that insomnia is a significant risk factor
for relapse
in abstinent alcoholics. Given these findings,
it
is surprising that very
little research has
been
conducted
to
determine whether:
the
insomnia
that occurs
with
military experiences
and/or
withdrawal
abates
with
time;
the
incidence
or
severity
of insomnia
is
associated
with
the
clinical
course
of alcoholism;
targeted
treatment
for insomnia
during
withdrawal
is
effective;
and
positive
treatment
response
for
insomnia
is
associated
with
duration
of
remission
and/or
risk
for
relapse
during abstinence. From the few studies that exist, the following
tentative claims can be made-
1)
alcoholism severity is associated with insomnia severity12; 2) insomnia
is a risk factor for relapse3"5;
3)
short-term
treatment
of
insomnia
during
first
year
of
recovery
improves
sleep
continuity
via
reduction
in both time to fall asleep and time awake during the
night. While the
results from these
studies are promising, most investigations were conducted
in small samples
(all but two studies had
final samples
of < 20 subjects)67 and were populated by patients with
poorly-defined
alcohol and
insomnia phenotypes (e.g., family history, age of onset, duration of illness,
illness severity
type and
subtype
of insomnia
[e.g.,
psychophysiologic
insomnia,
idiopathic
insomnia,
paradoxical
insomnia
and/or initial,
middle,
late,
or mixed insomnia]).
Further, most of the studies did not have follow-ups
that evaluated the durability of the insomnia treatment8"10 and how this was related to occurrence of
relapse
or
other
alcohol-related
measures
(e.g.,
alcohol
craving,
number
of
drinks
per day
the
occurrence
of binge
drinking,
etc.).
In
order to address some
of these
limitations
we
propose
to
conduct
a
study
of
standard
Cognitive
Behavioral
Therapy
for
Insomnia
(CBT-I)
in
60
alcohol-
dependent Veterans
during
the
first year
of their
recovery.
CBT-I was
selected
as the treatment
modality for several reasons.
First, CBT-I produces treatment outcomes that are as large
or larger
than pharmacotherapy in patients with Primary Insomnia1112, and there is a growing body of evidence
suggesting that
it is as effective in Secondary Insomnia13"15. Second, unlike pharmacotherapy
CBT-I
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exhibits
durable
results
following
treatment
discontinuation1617
and
less
likely
to
interact
with
medications being used for replacement therapy or management of comorbid illness. Third, there are
three
small-scale
studies
with
CBT-I
showing
that
the
regimen
is
applicable
in
the
context
of
alcoholism (i.e., subjects comply with/ benefit from the treatment)89'18.
Chronic
insomnia
has
been
associated
with
high-frequency
EEG
activity
((3
and
y,
16-50
Hz),
a
measure of cortical arousal.
In addition, there
is a diminished 5 and increased high-frequency NREM
EEG power among
patients with
insomnia,
as well as an association
between
high-frequency EEG
activity and
subjective
sleep
complaints.
High-frequency EEG
enhances
sensory
and
information
processing,
which
may
contribute
to
the
subjective-objective
discrepancy
that
often
characterizes
insomnia.
Evidence
is mixed regarding
insomnia-control
differences
in
high-frequency EEG
activity
during wakefulness.
However,
high-frequency waking EEG
activity
significantly correlates with
high-
frequency EEG activity during NREM and with self-reported hyperarousal symptoms.
These findings
support the hypothesis that high-frequency EEG power in insomnia
is a marker of CNS hyperarousal.
On
a
preliminary
basis,
we
will
investigate
the
role
of
CBT-I
treatment
in
decreasing
the
cortical
arousal in these patients.
Purpose of the Project:
Insomnia
is classified as both a primary disorder and a symptom of other disorders
in DSM
IV.
In the
DSM V insomnia will be classified as a primary disorder (i.e., as "Insomnia Disorder") when
it occurs
in
isolation and as
a co-morbid disorder when
it occurs as
a consequence
of another medical and
psychiatric illnesses. There are three major implications of this paradigmatic shift.
First, as a disorder
(vs. a symptom secondary to a primary
illness),
it can no longer be assumed that the "cause" of the
insomnia
is the primary disorder and that treatment for the primary disorder will
result
in a resolution
of the insomnia. Second,
as a co-morbid disorder,
insomnia can be conceptualized as co-occurring
condition
that may
interact with
other disorders and thus
result
in
greater
illness
severity
in one
or
both
conditions.
Third,
as
a
co-morbid
disorder,
insomnia
occurring
with
other disease
states may
complicate
the
treatment
of the
co-occurring
condition
(i.e.,
result
in
reduced
treatment
efficacy),
and/or the occurring condition will complicate the treatment of the insomnia.
These
implications are directly applicable to the insomnia that occurs
in association with alcoholism
and give rise to the following questions.
First,
is there evidence that insomnia
is a
risk factor for the
first
episode
of
alcoholism
(suggesting
that
insomnia
occurs
before
and
not
as
a
result
of
the
alcoholism).
Second,
data
show
that
alcoholism
severity
is
greater
in
patients
with
insomnia
as
compared to patients without insomnia and (conversely) that insomnia severity
is greater in patients
with alcoholism
as compared
to patients without alcoholism
(suggesting that the two disease states
interact as independent disorders to
reciprocally confer greater morbidity).
Third,
there
is evidence
that insomnia complicates the treatment of alcoholism
and/or that chronic alcoholism
is
associated
with perpetuation of insomnia (suggesting targeted treatment for both disorders is required when they
occur co-morbidly).
Given
the
newness
of
the
paradigmatic
shift,
it
comes
as
no
surprise
that
none
of
the
above
questions have been addressed
in a manner that allows for definitive answers. What is known
is that
insomnia
is
highly
prevalent
in
patients with
alcoholism,
and there
are
preliminary data
to
suggest
that
1)
insomnia
is
a
risk
factor for
recurrence
of
alcoholism;
2)
alcoholism
severity
is
greater
in
patients
with
insomnia
as
compared
to
patients
without
insomnia;
and
3)
targeted
treatment
for
insomnia in the context of alcoholism diminishes insomnia severity.
Showing
that CBT-I
is an
effective method
for managing
insomnia
in the context of alcoholism
will
provide
clinicians
with
an
additional
treatment
option
for
the
millions
that
suffer
from
insomnia
comorbid
with
alcoholism.
Demonstrating
that
the
clinical
course
of
patients
with
alcoholism
is
significantly improved by targeted treatment for insomnia will allow for a new and better standard of
care and
will open a new research window into "how and why" sleep disturbance
interacts with the
predisposition for, and severity of, alcoholism.
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I.
Describe the Research Questions or Hypotheses
Specific Aim
1
(Primary
Aim):
Determine
the
efficacy
of standard
8-week
CBT-I
intervention
in
recovering
alcohol
dependent
subjects.
Hypothesis
1:
Alcohol
dependent
participants who
receive
CBT-I, compared to the QDT, will exhibit greater improvement on the ISI and more durable treatment
gains on follow-up at 3 and 6 months. Secondary analyses will assess for group differences
in sleep
continuity (e.g., average SL, WASO, and TST) over all time points and will evaluate these parameters
relative to the meta-analytic norms.
Specific
Aim
2:
Investigate
whether
the
alcohol
dependent
Veterans
treated
with
CBT-I
have
reduced recidivism compared to those in the QDT control condition. Hypothesis 2: Alcohol dependent
participants who
receive
CBT-I,
compared
to QDT,
will
exhibit a
significantly
higher percentage
of
days
abstinent.
Secondary
analyses
will
assess
for group
differences
on
other
alcoholism-related
outcomes (e.g., craving, drinks per drinking day, and proportion of heavy drinking days).
Specific Aim
3:
Evaluate
if
subjects
treated
with
CBT-I
have
a
greater
improvement
in
daytime
functioning
as
compared
to
subjects
in
the
QDT.
Hypothesis
3:
Alcohol-dependent
participants
treated
with
CBT-I
will
exhibit
greater
improvement
in
subjective
daily
functioning
(health-related
quality
of
life
[primary
end
point]),
as
well
as
anxiety
and
depressive
symptoms
[secondary
end
points]).
Exploratory
Aim(s):
Assess
the
potential
relevance
of
genetic
and
neurobiologic
factors
as
predictors
of
illness
severity
and
treatment
outcome.
Specifically,
family
history
of
alcoholism
and
actigraphic data
will
be
acquired
during the course
of the
proposed
project and
evaluated
for their
relevance as correlates of clinical course.
J.
Primary Outcome Variable(s):
a)
The primary sleep outcome measure for the study is the insomnia severity (as assessed with the
Insomnia Severity Index scale (ISI)19'20;
b)
The primary alcohol outcome measure is percentage days abstinent (as assessed using the
Timeline Follow Back measure (TLFB)21"2(r
K.
Secondary Outcome Variable(s):
a)
The secondary sleep outcome measures are the traditional five sleep continuity values that are
obtained from the daily sleep diaries (averaged as weekly values for sleep latency [SL], number
of awakenings [NWAK], wake after sleep onset [WASO], total sleep time [TST] and SE%); other
outcome measures will include Pittsburgh Sleep Quality Index (PSQI), Composite Scale of
Morningness (CSM), Knowledge Assessment Questionnaire (KAQ), the Treatment Evaluation
Questionnaire (TEQ), and pre- and post-treatment evaluation questionnaire, Columbia-Suicide
Severity Rating Scale Baseline version (CSSR-B) & Columbia-Suicide Severity Rating Scale
Follow-up Screener (CSSR-S-FS), and the Epworth Sleepiness Scale (ESS).
In a subset of
subjects the polysomnographic sleep variables (sleep onset latency, sleep efficiency, wake after
sleep onset time) will also be evaluated.
b)
The secondary alcohol measures are alcohol craving (assessed with Penn Alcohol Craving Scale,
PACS)27"30, number of drinks per drinking day, and percent of heavy drinking days (assessed with
the TLFB)22-26, Short Index of Problems (SIP).
c)
The outcome measures for health and mood are the Short Form-12 item scale (SF-12)31, the
Patient Health Questionnaire 9-item scale (PHQ9)32'33, the Generalized Anxiety Disorders 7-item
scale (GAD7)3435, the Beck Depression Inventory-ll scale (BDI-II)3637 and the State-Trait Anxiety
Inventory (STAI)38, Columbia Suicide Severity Rating Scale (C-SSRS-B), and the Barratt's
Impulsivity Scale (BIS),
Interpersonal Support Evaluation List (ISEL), and Addictions Severity
Index (ASI), Columbia-Suicide Severity Rating Scale Baseline version (CSSR-B) & Columbia-
Suicide Severity Rating Scale Follow-up Screener (CSSR-S-FS).
d)
Family History of Alcohol Dependence will be assessed using the Semi Structured Assessment of
the Genetics of Alcoholism (SSAGA) - Family History Assessment Module (FHAM)3940.
e)
Other drug use will be assessed using the SCID-I module for abuse and dependence on other
drugs41 as well as with a Urine Drug Screen (UDS).
See Figure
1 and Table
1 for details.
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L.
Study Design and Methods:
1.
Is this a clinical trial?
DYES
|E|NO
1.1.
If yes, what type?
Check all that apply. N/A
□
Phase
I
□
Phase
II
□
Phase III
[
1.2.
If yes, this study must be registered on Clinicaltrials.gov.
Phase IV
2.
Design
2.1.
What research methods will be used
in the project?
Check all that apply.
Surveys/Questionnaires
Behavioral Observations
Focus Groups
ecimen Collection
Other (Describe)
Interviews
Chart Reviews
Randomization
Placebo
Deception
Audio Taping
Video Taping
Double-Blind
Withhold/Delay Treatment
><j Telephone Survey
Eight
Session
CBT-I:
General
Protocol.
Cognitive
Behavioral
therapy
is
conducted
in
8
sessions during which
subjects meet
individually with the
study
clinician.
Session
1
serves as
an orientation. No active treatment
is delivered
at this time. Sessions 2 & 3 are used to deliver
the three main components of the intervention which are Sleep Restriction (SRT)42'43, Stimulus
Control44"46, and Sleep Hygiene 47"49. All but two of the remaining sessions are dedicated to the
titration
of total
sleep time and
to ensuring
patient adherence. One session
(session
5)
entails
the
delivery
of
a
specific
form
of
cognitive
therapy.
The
cognitive
element
targeted
in
this
session
is modeled on Barlow's approach to the cognitive restructuring of catastrophic thinking
as
it
occurs
in
insomnia
with
panic
disorder.
This
approach
was
adapted
to
address
the
catastrophic thinking as
it occurs in insomnia
in relation to the consequences of poor sleep. The
final session (session 8)
is used to engage
in a relapse-prevention didactic,
i.e.,
to review first,
how insomnia becomes chronic and second, the strategies that are
likely to abort an extended
episode of insomnia. The specific details for each of the above interventions (e.g., titration rules,
stimulus control
rules,
etc.) and itineraries for each of the individual sessions are detailed
in the
Penn
treatment
manual
(published
by
Springer
in
2005
[hardback]
and
re-printed
in
2008
[paperback])50.
Quasi-Desensitization
Placebo
Therapy
(QDT).
This
form
of
placebo
therapy
has
been
commonly used
in
prior studies investigating behavioral interventions for insomnia9'13'5152. The
therapist
presents
the
QDT
as
a
means
to
eliminate
"conditioned
arousal,"
occurring
after
nocturnal arousal using 8 sessions on a weekly basis. The therapist initially helps the subject to
develop
a
chronological
12-item
hierarchy
of commonly
practiced
activities
on
awakening
at
night,
like opening eyes and
clock watching. As a
next
step,
the
subject develops 6
imaginal
scenes of himself/herself engaged
in
neutral
activities
like
reading
a newspaper. The therapist
then helps the subject pair the neutral scenes with the items from the
12-item
hierarchy, which
is then practiced by the subject > 2 hours before bedtime.
2.2.
Describe how randomization or other treatment assignment will be made. Subjects will
be block randomized using a computer generated randomizing sequence.
Participants are randomly assigned to the CBT-I group, or the QDT group. The study
biostatistician will create randomization sequences by family history of alcoholism
(separate sequences) using a pseudo-random number generator with block sizes of 4.
Two boxes of sequentially numbered, sealed, opaque envelopes will be prepared using
the randomization sequences and labeled "Family History" and "No Family History". At
the time of randomization, the first envelope,
in sequential order,
is pulled from the
appropriate box and opened to reveal the group assignment. All the staff conducting
assessments will be blinded to the allocation of treatment arm with the exception of Dr.
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Findley, the BSM treatment provider, Ms.
Barilla the person overseeing treatment
allocation, and Dr. Harb, the monitor for BSM treatment for the study.
2.3.
For retrospective research studies, provide the "look-back" period,
(e.g., December 1,
1999 through December 31, 2008.) N/A.
3.
Study Duration
3.1.
Provide the estimated length of time to enroll
all subjects and complete the study. Five
years.
3.2.
Explain the expected duration of subject participation including any follow-up. Eight
months.
3.3.
Specify the projected date of completion of the proposed study. Dec. 2018.
4.
Drug Information. Not Applicable.
5.
Investigational Device. Not Applicable.
M.
Does this project involve international research?
QYES
KlNO
N.
Study Procedure. Please see Table
1
for all the study-related procedures.
The actigraph:
A wristband that the patient wears on his/her non-dominant arm continuously over a
1 week period, measures rest/activity as a surrogate marker for sleep and wakefulness).
Actiwatch® (Mini Mitter Company) recordings will be obtained to measure duration of nocturnal
inactivity as a proxy for sleep duration during simultaneously recorded, time-linked Stardust II®
recordings. Estimated sleep time, the primary actigraph outcome measure, will be used to calculate
the total sleep time and quality of sleep at home. Actiwatch®
is a compact, wrist-worn, battery-
operated activity monitor that utilizes a motion sensor known as an "accelerometer" to monitor the
occurrence and degree of motion. Actiwatch® is programmed to collect data using the Sleepwatch
software application that runs on an IBM-compatible PC. A sleep diary will be filled out by the
subject while using the actigraph. The sleep diary is a subjective log maintained by the subject of
the times he falls asleep and awakens over the 24-hour period. The sleep diary filled out by the
subject (on the days of the actigraph use) will be used to assess and clarify the sleep wake data as
measured by the actigraph. The actigraphy will be done at baseline and during the treatment study
weeks. Conduct of the actigraphy during the post-treatment follow-up at 3- and 6-month visits will
be deemed optional.
Overnight in-laboratory polvsomnography (PSG): a registered polysomnographic technologist will
perform the overnight polysomnographic sleep studies at the CMCVAMC sleep center.
The
polysomnograms will include electroencephalography, electromyography, electrooculography,
electrocardiogram, pulse oximeter, and plethysmography to monitor for chest muscle activity.
Overnight polysomnograms will be performed using standard techniques (12).
The following
signals will be recorded using a computer data acquisition and analysis system (Mallinckrodt,
Pleasanton, CA):
electroencephalogram (C3A2 and O2A1),
bilateral electrooculograms, chin
muscle activity,
bilateral anterior tibialis electromyogram,
rib cage and abdominal movement, nasal
pressure and snoring (Pro-Tech, Woodinville, WA), body position, and heart rate and oxygen
saturation by pulse oximetry (Ohmeda, Louisville, CO).
The PSG will be conducted in a subset of
up to 20 subjects (up to 10 in the CBT-I arm and up to 10 in the QDT arm)
in an equitable
distribution across both treatment arms and pending availability of funds. Each subject will have
complete 2 PSG studies, one at baseline and one at the end of treatment (within weeks 7-8 of the
treatment visits).
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1.1.
Outline all study procedures.
Table
1: A List of Assessments Involved with
Participation
in this Study
Table 3. Data Collection Table
Treatment-Related visits
Acronyms
Type
III Monitor = Type
III
portable sleep monitor
PSG = Polysomnography
PSQI = Pittsburgh Sleep Quality
Index,
CSM = Composite Scale of
Morningness,
KAQ = Knowledge Assessment
Questionnaire,
TEQ= Treatment Experience
Questionnaire;
EQ=BSM Expectancy
Questionnaire;
ISI = Insomnia Severity Index,
SCID- = Structured Clinical
Interview
for DSM-IV-TR Axis
I
Diagnoses,
SSAGA-FHAM = Semi-structured
Assessment for the Genetics of
Alcoholism,
CIWA = Clinical Institute
Withdrawal Assessment for
Alcoholism scale;
UDS = Urine Drug Screen,
SIP - Short Index of Problems
Scale,
TLFB = Time Line Follow Back,
PACS = Penn Alcohol Craving
Scale,
BOMC = Blessed Orientation
Memory Concentration test;
C-SSRS-B = Columbia Suicide
Severity Rating Scale - Baseline
version
PHQ9 = Patient Health
Questionnaire 9-items,
BDI = Beck Depression Inventory,
STAI = State Trait Anxiety
Inventory,
GAD7 = Generalized Anxiety
Disorders-7 Questionnaire,
PCL-S = PTSD Checklist -
specific
QOL = Quality of Life,
SF-12 = Health-Related Quality of
Life, Short Form 12,
TBI Screener = Traumatic Brain
Injury Screener,
ESS = Epworth Sleepiness Scale
ASI = Addictions Severity Index
ISEL = Interpersonal Support
Evaluation List
C-SSRS-FS = Columbia Suicide
Severity Rating Scale - Follow-up
Screener version
W = Week #,
F/U = Follow up visit.
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QOL
Medical
Genetic
H&P
PCL-S
CSSR-S-FS
ASI
ISEL
SF-12
Charlson's Index
TBI Screener
Blood Sample
History &
Physical Exam i
i
iI
1
- for research purposes,2 - for clinical purposes,3
- routine procedures performed solely for research purposes.
1SDS-CL-Sleep Disorders Checklist; 1&2Type
III Portable Sleep Monitor; 1&2 ISI; 1&2 Sleep Diary;1&2 actigraphy;3 PSQI;3 CSM;3, KAQ 3 TEQ,3
SCID-I; 1SSAGA - Semi Structured Assessment for the Genetics of Alcoholism;1&2 CIWA - Clinical Institute Withdrawal Assessment for Alcohol;
1&2 UDS;3 SIP; 3TLFB; 3PACS; 1S2 Breathalyzer; U2; 1&2 BOMC - Blessed Orientation Memory Concentration test; PHQ-9;3 C-SSRS-B;3 BIS;
1&2BDI-II; 1&2STAI; U2 GAD-7; U2 PCL-S;3 SF-12;3 Charlson's Index;
1 Blood sample, ESS. ISEL, CSSR-S-FS, & ASI
1.2.
Explain
if and how the follow-up of subjects will occur. The subjects will be
initially
assessed
for
eligibility
over the
baseline
assessment
period
that
will
last
for about
a
month. This baseline assessment will involve assessments of their alcohol use disorder
history, screening for other drug use, assessment for psychiatric disorders, assessment
for sleep disorders, and a history and physical examination; see Figure
1
below.
On successful completion of the baseline assessments subjects will be randomized into
the
treatment
arms
(CBT-I
or
QDT).
They
will
be
treated
for
8-weeks,
and
will
be
followed
up
for
8
sessions.
After
completion
of
the
active
intervention
they
will
be
followed
up
at
3
months
and
6
months
from
the
date
of
the
completion
of
either
intervention.
All the follow up visits will include assessment of symptoms in the domains
of
alcohol
use,
psychiatric
symptoms,
insomnia
and
sleep-related
symptoms.
If
a
subject
decides
to
end
treatment
prematurely
or
is
unable
to
attend
any
following
sessions
after
completing
the
first
treatment
session
on Week
1,
we
will
continue
to
collect follow-up data
at the time
points
of Week
8, and follow-ups
at 3-months and
6-
months.
Figure
1: Study Ovtrvi«w
Pf*60 Insomnia * Alcoholism
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t
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| In
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IO4urd*ri, Sf 12 • Short Form 11 Ham, WlQ-M>Work(
oral TN
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Pivchlatrk: BDl-ll, STAI. PHQ-9. GAD-7
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1.3.
Describe where, how and who will be conducting study procedures,
a) Screening
(in
person
or
over
the
phone)
-
will
be
performed
by
the
study
coordinator;
b)
Assessments - at
baseline and
for the follow-up
visits
will
be conducted
by the study
coordinator (in-person,
via mailed packet with a self addressed return envelope without
date
of assessment,
or,
phone for follow-ups);
c)
Intervention (CBT-I
or QDT)
- will
be
conducted by the behavioral sleep medicine specialist associated with the study (TBA);
d)
Urine drug screen - will be conducted by the study coordinator or obtained from the
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1.4.
1.5.
patient's
electronic
medical
record
if
one
was
done
during
the
time
the
patient
is
undergoing
the
baseline assessment
period;
d)
Blood
sample
-
will
be drawn
up and
processed
by
Dr.
Chakravorty,
or
the
designated
staff
member
associated
with
the
study, including the study coordinator after IRB approved training and at the CMCVAMC
laboratory services as a back-up option;
e) Overnight polysomnography will be done
at
the CMCVAMC sleep center by their credentialed sleep technicians. Dr. Chakravorty will
serve as a back-up staff member for any of the study-related procedures.
If a survey study, specify the estimated amount of time that subjects will need to
complete the questionnaires/tools.
N/A
If
a
blood
draw,
specify
the
amount
of
blood
to
be
drawn
in
milliliters
and
in
teaspoonful or tablespoonful and
specify how often and where the blood will
be
drawn. About one tablespoon (~15ml).
2.
Data Collection
2.1.
Provide
2.1.1.
2.1.2.
The mode
of data
collection,
e.g.
telephone,
in-person,
questionnaire,
interviews. The
initial screening will occur over the phone or in person using
the
IRB-approved
telephone
screening
guestionnaire
(see
attached
telephone screen) similar to the one used
in our CBT-I
pilot study. Veterans
who
have
positive
screen
will
undergo
baseline
evaluations
to
further
determine study eligibility. Once eligible they will be randomized
into one of
the
study arms and treated
for 8-weeks followed
by
a
post-study follow up
visits
at
3
months
and
6
months.
All
the
assessments
(in-person,
questionnaires,
and
interviews)
will
occur
during
the
baseline
phase,
treatment phase and post-study follow up phase, and will target evaluation of
symptoms pertaining to sleep and insomnia, alcohol consumption (and other
drugs
if
applicable),
and
psychiatric
symptoms;
see
Table
1
for
list
of
assessments and
the time frame
for
their
use,
as
well
as
Figure
1
for the
study design.
If the subject is unable to make
it to the CMCVAMC during the
week 8 time point or for the 3-month or 6-month follow-up, then the research
team
will
complete
the
questionnaires
with
the
subject
over
the
phone
or
have
the
subject
complete
them
at
home
via
mailed
questionnaire
packet
with telephone follow-up when necessary.
The precise plan for how data is to be collected or acquired. Most of the
assessment measures will
involve
interviews
(e.g.
for the SCID form,
or for
the
initial
CBT-I
session).
During
the
treatment
or
follow-up
phase,
if
the
subject
is unable to meet the research team
at the CMCVAMC to complete
the
study questionnaires and
interviews
in-person,
then the
research team
will complete the interviews and questionnaires by phone with the subject or
have the subject complete the questionnaires via
mailed packet and follow-
up
by telephone
if any
interviews
are
needed.
The
only
exceptions
to
this
rule are for the actigraphs and the portable sleep monitors. Actigraphs will be
worn
on
the
wrist
for
a
few
days
at
a
stretch
and
the
Veteran
will
be
maintaining
a
sleep
diary
for
the
sleep-wake
schedule.
The
monitor
has
sensors
attached
to
the
body
recording
oxygen
saturation,
airflow
(nasal
pressure),
thoracic
movements,
snoring,
body
position
and
the
heart
rate.
The
apparatus
measures
nasal
pressure,
which
is
an
accepted
surrogate
marker of air flow (instead of using oro-nasal thermistors, used
in the earlier
portable monitors); see Table
1
for details on the assessment measures and
the time frames of assessments. All the staff conducting assessments will be
blinded to the
allocation
of treatment arm with the exception
of
Dr.
Findley,
the
BSM
treatment
provider,
Ms.
Barilla
the
person
overseeing
treatment
allocation,
and
Dr.
Harb,
the
monitor
for
BSM
treatment
for
the
study.
Overnight polysomnography data,
will be obtained by the sleep technologist
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at the CMCVAMC sleep center. The data will be captured electronically and
will
be analyzed
by the
physicians
at the CMCVAMC VISN 4 Sleep Center
sleep center as well as the research team.
Exact
location
where
data
will
be
collected.
The
initial
screening
will
be
conducted
over the
telephone
or
in
person,
either within
the
MIRECC
office
space of Room # 228 or in any available locked
office space
in the ARU/MHC
on the 7th floor or 2nd floor of the main building.
If the subject is unable to travel
to the CMCVAMC for the week 8 or follow-up assessments, then the research
team
will
complete
them
with
the
subject
by
phone
or
have
the
subject
complete them
via
mailed
packet
with
telephone
follow-up
if
necessary.
The
source
documents
will
be
stored
in
the
locked
desk
drawer
of
the
study
coordinator (in room # 228). All the rest of the source documents will be stored
in the above-mentioned locked desk drawers of the study coordinator (in room
#
228).
Data from REDCap
will
be
stored on VA servers
located
within
a VA
data center inside the VA firewall which afforded the same network protections
as
all VA sensitive
clinical data. The electronic data,
including any data
pulled
from
REDCap
see
below
for
details
Data
from
the
actigraph
will
be
stored
locally
on
the
desktop
and
backed
up
on
compact
disks
and
stored
in
the
locked office drawer of the research assistant in the MIRECC office space with
restricted
access.
Data
from
the
polysomnographic
sleep
studies
will
be
captured
at
the
CMCVAMC
Sleep
Center.
The
data
from
the
scored
polysomnographic studies will be transferred via compact discs to the MIRECC
VISN-4 secure databases.
2.1.3.
Data management will occur through the VA REDCap (Research Electronic
Data
Capture),
a
secure
web
application
and
back-end
database
model,
developed at Vanderbilt University with collaboration from a consortium of
institutional
partners.
Approved
study
staff
will
enter
data
directly
into
REDCap, which obviates the need for transferring written data into electronic
form; this significantly improves the quality of data. The VA has licensed its
own
version
of REDCap housed on VA
servers
located
within a VA
data
center
inside
the
VA
firewall
and
therefore
afforded
the
same
network
protections
as
all
VA
sensitive
clinical
data.
REDCap
was
developed
specifically around HIPAA Security guidelines and
is recommended to Penn
Medicine researchers by our Office of Human Research.
Relevant HIPAA-
compliant
features
include
password-protected
access
to
the
system,
restriction of access
to
specific
clinical
trial
data to
designated
users,
audit
trails of access and data updates, and built-in de-identification functions that
can
be
used
when
exporting
data
for
analysis.
REDCap
has
been
disseminated for use
locally at other institutions and currently supports
170
academic/non-profit
consortium
partners
on
six
continents
and
13,000
research
end-users
(www.project-redcap.org).
Approved
study
staff
can
access REDCap through a web-based interface and securely input data from
any location at the time of data collection minimizing the need for travelling
with either electronic or paper versions of sensitive information.
VA REDCap database administrators
will have control
over electronic access
rights
to
REDCap
databases.
Only
VA
IRB
approved
individuals
will
be
granted access to this database. This database keeps time-stamped information
on people accessing, inputting, and altering data in the database.
2.1.4.
Exact location where data entry will take
place.
Data entry will
primarily
take
place
in the locked
office space
of the MIRECC
(room # 228B) which
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has
a
restricted
access
to
authorized
staff
only.
Data
entry
may
occur
secondarily
in the Dr.
Chakravorty's locked
office space (Room # 218,
Bldg.
3),
and
in the available locked
private
office space
of the ARU
or the MHC
on the seventh floor of the CMCVAMC main
building. The PSG data will be
acquired
and
evaluated
at the CMCVAMC
similar to
other studies done
in
the past.
2.1.5.
The
"title"
of
individual(s)
collecting
the
data and
analyzing
the
data,
e.g.
principal
investigator,
research
coordinator.
Principal
investigator
(Dr. Chakravorty), study coordinator, the behavioral sleep medicine provider,
phlebotomy
staff at the CMCVAMC
laboratory services,
and any other staff
designated by Dr. Chakravorty after approval of the CMCVAMC -IRB.
2.2.
Provide a time line for each aspect of the study. See Table 2 for details related to
the proposed activities associated with the study.
Table 2. Gantt Chart of Proposed Activities Related to the Project
Set-up
Enrollment
Closeout of Study
Education
Data Analysis
Dissemination
Merit Review Application
Yeari
Q1
Q2
Q3
Q4
Year 2
Year 3
Year 4
Year5
Q1
Q2
Q3
Q4
mm
Q1 =
1s' Quarter, Q2 = 2"° Quarter, Q3 = 3™Quarter, Q4 = 4tn Quarter
2.3.
Chart/Records/Data Review (retrospective and/or prospective)
2.3.1.
Provide the planned or approximate number of charts/records/data to be
accessed
2.3.1.1.
CMCVAMC All subjects
2.3.1.2.
Other site. N/A.
2.3.2.
Does this protocol employ an Honest Broker? DYES
KINO
2.3.2.1.
If yes, provide name of individual. N/A
2.3.2.2.
If
no,
explain who
will
access
the
charts/records.
Study-related
staff; they will currently include Dr. Chakravorty, the study coordinator,
and the behavioral sleep medicine specialist.
2.3.2.3.
Describe
from
what
database
charts/records/data
will
be
accessed.
Initial
prescreening
may
be
conducted
by
evaluating
the
CPRS
(the
electronic
clinical
charts
of the
patients)
in
order to
alert
their providers about the Veteran's option of participating
in this study.
After obtaining
informed consent for the Veteran
after he has signed
the HIPAA form, we
will access
his
clinical
chart to evaluate for past
and
current
clinical
assessments
and
treatments
as
part
of
his/her
baseline assessments.
3.
Future Use of Data and Re-Contact,
if applicable.
3.1.
If any of the
participant's data are going to be retained after the study for future
research, the following information must be provided to the participant: The blood
sample for the genetic analyses.
This explained
in the
informed consent form and the
HIPAA form.
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3.2.
Where
will the data be stored? The
blood samples
for the
genetic analyses
will
be
stored
at a freezer space within the CMCVAMC (Research
Building,
4th floor, freezer
room), as designated by the CMCVAMC R&D
staff. When
all the samples have been
collected
and
samples
are
ready
for
analyses we
will
transfer
the
samples
with
the
coded identifier (and without any of the 17 HIPAA identifiers) from the CMCVAMC to the
designated
laboratory
at
the
University
of
Pennsylvania
after
obtaining
the
required
CMCVAMC
-IRB
authorization.
The
samples
will
be
destroyed
at
the
University
of
Pennsylvania after the genetic tests have been conducted.
3.2.1.
Who will have access to the data? The Principal
Investigator and the study
coordinator and the
regulatory agencies (CMCVAMC
-IRB,
and designated
VA
CS
R
&
D
staff).
The
staff
associated
with
the
genetic
analyses
laboratory and the statistician,
both within the University of Pennsylvania will
have access to the coded data (without the 17 HIPAA identifiers).
3.3.
If the subject is going to be re-contacted in the future about participating in future
research, this must be specified.
Describe the circumstances under which the
participant would be re-contacted whether within the VA or outside the VA. N/A
3.3.1.
If subjects will receive aggregate study results at the end of the study,
the informed consent document must contain this information. N/A
4.
Specimen Collection
4.1.
Give the source of all specimens and whether they were collected for research,
treatment or diagnosis. Blood samples will be collected for genetic analyses related to
research.
4.2.
State where specimens
will
be
stored, secured and when
discarded.
The
blood
samples for the genetic analyses will be stored at a freezer space within the CMCVAMC
(Research
Building,
4th
floor,
freezer room),
as designated
by the CMCVAMC R&D
staff. When
all the samples have been collected and samples are ready for analyses we
will
transfer the
samples
with
the
coded
identifier
(and
without
any
of the
17
HIPAA
identifiers)
from
the
CMCVAMC
to
the
designated
laboratory
at
the
University
of
Pennsylvania
after obtaining the required CMCVAMC -IRB authorization. The samples
will
be
destroyed
at the
University
of
Pennsylvania
after the
genetic
tests
have
been
conducted.
4.3.
Explain
how
destruction
of samples
will
be
substantiated.
The
samples
will
be
destroyed
at the
laboratory within
the
University
of Pennsylvania
using
their standard
protocols for destruction. A form certifying the destruction of the samples will be issued
by the staff from the laboratory at the University of Pennsylvania.
O.
Genetic Testing,
if applicable
1.
Explain
if the study
is looking for an association between a genetic marker and a specific
disease or condition,
but at this
point
it
is
not clear
if the genetic marker has
predictive
value. The future study will explore for an association between
single nucleotide polymorphisms
(SNPs) of candidate genes and their relation with subjective and
objective insomnia variables
in
the recovering alcoholic subjects. At this point
it
is not clear
if the genetic marker has a predictive
value.
1.1.
The uncertainty regarding the predictive value of the genetic marker is such that studies
in this category will not involve participant counseling.
1.2.
Describe
if the study
is based on the premise that a link between a genetic marker and
a
specific disease or condition
is such that the marker
is
clinically
useful
in
predicting
the development of that specific disease or condition.
N/A.
1.3.
Will the subject be notified of the results and the provision for genetic counseling?
□Yes
E3 No □N/A
1.3.1.
If yes, explain further.
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1.4.
If
biological
specimens
are
used
in
this
protocol,
please
respond
to
the
following
questions by checking the appropriate box:
1.5.
Does the project involve genetic testing?
Will specimens be kept for future, unspecified use?
c.
Will samples be made anonymous to maintain confidentiality?
d.
Will specimens
be
destroyed
after the
project-specific
use
is
completed?
e.
Will specimens be sold
in the future?
f.
Will subjects be paid for their specimens now or in the future?
g.
Will
subjects
be
informed
of
the
results
of
the
specimen
testing?
h.
Are
there
any
implications
for
family
members
based
on
specimen testing results? (If yes, they may be participants.)
YES
El
□
□
□
NO
□
LJ
El
El
N/A
□
LJ
□
□
1.6.
Will subjects be informed of results obtained from their DNA?
Will specimens be de-identified? QYES
KINO
□N/A
1.5.1.
If yes, please describe the procedures to be used.
The specimens will be
coded using study specific identification number.
1.5.2.
Include at what point in the process the specimens will be de-identified.
The
specimen
will
receive
a
coded
identification
(not
associated
with
any
combination of his/her social security number) number at the time of collection
and
will
not
have
any
of the
17 HIPAA
identifiers
associated
with
it.
Prior to
genetic analyses the data will be transferred to the designated laboratory of the
University
of
Pennsylvania
with
an
approval
obtained
from
the CMCVAMC
-
IRB. On completion
of the genetic analyses, the data from the test results
will
be
retained
at
University
of Pennsylvania
laboratory database where
a
fresh
code
will
be
issued
to
identify
the
genetic
results
(independent
of the
code
allocated at the CMCVAMC). This recoded data will be pooled with the results
of other similar subjects who have had the genetic analyses
at the
laboratory
and
the
statistical
analyses
will
then
be
conducted.
In
summary,
the
blood
sample
for
genetic
analyses
will
initially
be
coded
at
CMCVAMC
with
a
identification code not related to any combination of his social security number.
During
the genetic
analyses
procedure
at the
University
of Pennsylvania
the
sample will be recoded again with a fresh code and the results
will be pooled
with the
results of other subjects on whom the same genetic analyses
will be
conducted.
Describe what measures will be taken to minimize the following
risks from breaches of
confidentiality and
privacy
resulting from
participating
in THIS aspect of the research
project:
1.6.1.
Physical:
The
paper
pencil
data
relating
to
the
genetic
assessment
will
be
stored
in the locked desk drawers
in locked offices of MIRECC (Room 228 B),
and the Pi's locked office space (Room # 218,
Bldg.
3).
Electronic data relating
to
genetic
assessment
will
be
stored
in
the
password
protected
online VA
servers in the MIRECC (\\vhaphifpcmirecc\Research Studies\Chakravorty). The
physical
samples
will
be
stored
with
only
the
coded
unique
identification
numbers and without any of the 17 HIPAA identifiers.
1.6.2.
Psychological:
Prior
to
sample
collection
patient
will
be
notified
that
the
testing
is
purely to assess
for research
related
purposes,
and
not for
clinical
testing of any disorder. Every effort will be made by the study staff to alleviate
or
minimize
emotional
discomfort
associated
with
the
collection
of the
blood
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R&D Service (151)
sample and explain to the
patient that the sample
will be stored
using only a
coded identifier and without any of the 17 HIPAA identifiers.
1.6.3.
Financial:
Patient
will
be
notified
that
the
genetic
sample
donation
will
be
voluntary in nature.
1.6.4.
Social:
Since
the
blood
sample
will
be
stored
only
with
a
coded
identifier
(without the
17 HIPAA
identifiers) and the genetic analyses
will be conducted
to assess for experimental associations of SNPs with insomnia symptoms, the
subject will be explained that the social ramification of the loss of blood sample
will be minimal to none.
1.6.5.
Legal harm: Since the blood sample will be stored only with a coded identifier
(without the
17 HIPAA identifiers) and the genetic analyses will be conducted
to assess for experimental associations of SNPs with insomnia symptoms, the
subject will be explained that the legal ramification of the loss of blood sample
will be very minimal to none.
P.
Banking of Collected Specimens
1.
Will collected specimens be banked?
IEIYES
QNO
QN/A
1.1.
If yes,
specify the
location where specimens
will
be
banked.
Within
a
designated
freezer space within the CMCVAMC (Research Building A218) as recommended by the
CMCVAMC -IRB.
1.1.1.
If the
location
is
a
non-VA
site,
has
the
mandatory
approval
from
the
Chief
Officer
of
Research
and
Development
(CRADO)
been
obtained
through
submission
of
a
tissue
banking
application
(VA
Form
10-0436
-
Off-site
Application for an Off-site Tissue Banking Waiver)? DYES
lElNO
DN/A
1.1.2.
If applicable, attach a copy of the VA Form 10-0436
1.2.
Explain how destruction
of banked samples will
be substantiated. After transfer to
the
designated
laboratory
at
the
University
of
Pennsylvania
with
CMCVAMC
-IRM
approval,
the samples
will be evaluated for the genetic analyses. The samples will be
destroyed
at the
laboratory within the
University
of Pennsylvania
using
their standard
protocols for destruction. A form certifying the destruction of the samples will be issued
by the laboratory staff at the University of Pennsylvania.
Q.
Subject Recruitment (characteristics of the study population)
1.
Provide the planned or targeted enrollment at:
1.1.
CMCVAMC-86
1.2.
Other sites - N/A
1.3.
Not applicable; chart review or use of previously collected data - □
2.
Screening and/or Eligibility Requirements
2.1.
Describe:
2.1.1.
Inclusion criteria: a) Male and female Veterans between the ages of 21
and
70 years;
b) DSM IV diagnosis of alcohol dependence over the past year (as
determined by the SCID-I41);
c) Self-reported sleep latency or wake time after
sleep onset >30 min on
three or more
nights
per week for >1
month and
a
score
of >15
on
the
Insomnia
Severity
Index
(ISI)20; d)
No
current
alcohol
withdrawal symptoms
at
baseline: CIWA score
<
8
(CIWA53
is the
Clinical
Institute
Withdrawal
Assessment
scale
for
alcohol
withdrawal
signs
and
symptoms);
e)
abstain for > 4 weeks from heavy drinking and < one year of
abstinence
from
alcohol
use
prior
to
the
baseline
study
assessments
as
assessed by subjective report or breathalyzer;
f) Ability to speak, understand
and print in English, g) Capacity to give written informed consent.
2.1.2.
Exclusion
criteria:
a.
DSM-IV
criteria
for
dependence
on
any
other
substance including benzodiazepines, and excluding nicotine dependence;
b.
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Positive urine drug screen for opioids,
cocaine,
or amphetamine. Tetra Hydro
Cannabinol
(A9-tetrahydrocannabinol
is
one
of
the
main
psychoactive
ingredients of marijuana)
is not considered an exclusion
criteria;
c.
Patient
is
currently
in
alcohol
withdrawal
as
assessed
by
the
Clinical
Institute
Withdrawal Assessment Scale (CIWA) total score > 8
53; d. A lifetime DSM-IV
diagnosis
of
Bipolar
I
or
II
disorder,
Schizophrenia,
or
other
psychotic
disorder,
as determined on
the
SCID-I41,
and
current
(past
month) DSM-IV
diagnosis
of
Major
Depressive
Disorder;
e.
Presence
of
unstable
medical
diagnosis
e.g.
congestive
heart failure,
leading
to
interference with
sleep,
as
reported
on
history,
examination,
and/or
review
of
clinical
chart
during
baseline assessments;
f.
Current use
of any medications that may
influence
the drinking
behavior,
e.g.
naltrexone or acamprosate;
g.
Evidence of severe
cognitive
impairment
as
assessed
by
the
BOMC
(Blessed
Orientation-
Memory-Concentration
test weighted
score >
16);
h.
Untreated
patients with
the diagnosis
of moderate-severe obstructive sleep apnea with
Total Apnea-
Hypopnea
Index (AHI-T) of >
15 events/hour of sleep;
i.
Subject's
inability to
give informed consent.
2.2.
List
all screening and/or eligibility requirements. A Veteran who
is
less than
or 70
years old,
suffers from alcoholism and insomnia, and
is currently sober or not indulging
in
heavy
drinking
within
the
last
one
year,
not
currently
dependent
on
other
drugs
(excluding
nicotine
or
marijuana),
is
medically
and
psychiatrically
stable,
and
is
interested
in
participating
in
the
research
study
and
eligible
for
care
within
the VA
healthcare system.
2.3.
Explain any special
test or evaluations
potential subjects may have to undergo
before
they
are
actually
determined
to
be
eligible
for
the
study.
Subjects
will
undergo an extensive baseline evaluation to determine their eligibility and their ability to
participate
in
the
study.
These
tests
will
include
the
following:
a)
Insomnia
Severity
Index
(to assess their current insomnia symptoms);
b)
Structured Clinical Interview for
DSM-IV
diagnoses
(SCID,
to
assess
their
current
psychiatric
status);
c)
Time
Line
Follow Back measure
(TLFB,
to
assess
their
quantity
and
frequency
of
alcohol
use,
nicotine
use, and cannabis use
in the
last 90 days
of drinking within the past year);
d)
Type
III portable sleep monitor to screen for moderate - severe obstructive sleep apnea
syndrome;
e)
History
&
Physical
examination
(to
assess
for
medical
stability
to
participate
in
the
study);
f)
Urine
Drug
Screen
-
to
screen
for
the
use
of
other
psychoactive drugs.
2.4.
Not Applicable; subjects not recruited; chart review. □
3.
If applicable, indicate what populations will be targeted for recruitment as participants.
Check all that apply.
Males
Females
Inpatients
Outpatients
VA Employees
Non-English Speaking*
Veteran Family members***
Non-Veterans***
Other (Specify)
Not Applicable, chart review
□
□
□
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3.1.
**For non-English speaking subjects -
If an investigator proposes to use a participant
population that does not speak or read English, a copy of the translated document, as
well as the English version, needs to be forwarded to the IRB for approval.
Translator
certification
is also required. N/A
3.2.
***lf non-veterans will be recruited for this study, explain why sufficient veterans are not
available to participate in the project [VHA Handbook 1200.5, paragraph 16a]. Veteran's
spouses/partners, caregivers, etc. are considered non-veterans for the purposes of this
study.
N/A
3.3.
***Has approval to recruit non-veterans been received from the ACOS/R&D and
Medical Center Director?
3.3.1.
[X] Not Applicable
3.3.2.
□Pending
Does this project target a specific race or ethnic group as participants? DYES
If yes, check all that apply.
^__^
NO
Race
American Indian or Alaskan Native
Asian
Black or African American
Native Hawaiian or other Pacific
Islander
Black, not of Hispanic origin
White, not of Hispanic origin
Other
□
Ethnicity
Hispanic or Latino
Not Hispanic or Latino
Other
D
rr
5.
4.1.
Provide justification why this/these group(s) was/were chosen
What is the age range of participants?
Check all that apply.
Children (Under 18) Requires Waiver from CRADO (VHA
Directive 2001-028, Research Involving Children)
Young Adults (18-21)
Adults (22-70)
Seniors (Over 70)
Over 89
Not Applicable, chart review
Are there specific reasons why certain populations (i.e., age, gender or ethnic groups)
are excluded as participants?
KlYES
QNO
QN/A
6.1.
If yes, specify reasons. Alcohol dependent Veterans older than 70 years of age may
have
a
poor
health
status,
more
likely
to
have
psychiatric
disorders
in
addition
to
a
higher level of insomnia.
Further, they may have difficulty with the demands associated
with
participation
in this study, which includes multiple baseline
visits, weekly follow-up
visits,
the
post-intervention
follow-up
visits,
use
of the
actigraphy and
recording
daily
sleep diaries at home and the use of the portable sleep monitor.
Does the project require enrollment of the following classes of participants?
a.
Employees
b.
Individuals with impaired decision making capability
c.
Pregnant women
d.
Economically and/or educationally disadvantaged persons
YES
lx|
W
NO
X]
X]
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R&D Service (151)
e.
Prisoners
f.
Illiterate,
limited, or no English language proficiency
g.
Terminally
ill patients
u
==
M
—
7.1.
If applicable, what
is the justification
for
including
any
of the above classes
of
participants in the project?
Only those employees who are Veterans themselves and
are
eligible
for care within
the VA systems
will
be
eligible
for
this
study.
Many
of the
Veterans
recovering from
alcoholism
are
unemployed and
reside
in
shelters and
also
suffer from insomnia; they also have limited social supports. Participate in this treatment
study
will
help
them
to
understand
their
illness,
increase
contact
with
health
care
providers,
receive
reminders
for
upcoming
appointments
with
providers
within
the
system
when
needed
as
we
have
done
in
the
past,
help
them
monitor
their
own
symptoms,
develop a sense of overall
efficacy, decrease their sense of loneliness and
isolation, and help them promote behaviors associated with health
living.
7.2.
If the project requires enrolling any of the above classes of participants describe
any project-specific measures or special considerations, steps, or safeguards to
ensure that these individuals are adequately protected. Only those employees who
are
Veterans
and
are
eligible
for
care
through
the
VA
system
will
be
eligible
for
participation
in this
study.
In
line with experiences from our current study and
our past
clinical
trial we
will
use
standard
procedures
to
recruit,
treat
and
follow-up Veterans
recovering from alcoholism.
In addition, our research staff is trained to be sensitive and
to
be
sensitive
to the unique needs
of Veterans from
an
economically disadvantaged
background.
8.
Describe the exact plan how subjects will be identified and recruited for the study.
8.1.
Discuss
methods,
e.g.,
referrals
from
physician
offices,
clinics,
programs,
or
through
advertisements
and
brochures.
The
prospective
subjective
will
enter
the
study from the following mechanisms:
1)
referral from providers and case managers;
2)
self-referrals
in response to advertisements posted within the CMCVAMC, and
satellite
VA
veteran
housing
support
programs
(IMPACT,
Fresh
Start,
Snyder
House,
and
Veteran's Multi-Service Center (VMC);
3) self-referrals
in response to the advertisement
posted
in Craigslist.com.
8.2.
If using a clinic, be specific about who will identify the potential subject and how
that information will be transmitted to the research staff. The potential subjects will
be identified by the Veterans providers or by the research staff who will then discuss the
study with the
identified Veteran's provider or case manager. The following
clinics and
programs will be targeted for recruitment of Veterans:
1) Addiction Recovery Unit (ARU)
of the CMCVAMC;
2)
Mental
Health
Clinic (MHC)
of the CMCVAMC;
3)
Primary Care
Clinics (PCC) within the CMCVAMC; 4) Community Based Outpatient Clinics (CBOCs)
associated with CMCVAMC;
5)
Behavioral Health Laboratory (BHL) of the CMCVAMC;
6)
inpatient
psychiatry
units;
7) CMCVAMC Sleep Center;
8) Veteran
housing
support
programs (IMPACT, Fresh Start, Snyder House, and VMC,).
8.3.
If snowball method will be used, discuss the process and how the first individuals
will be recruited. N/A.
8.4.
Describe
how
information
will
be
disseminated
to
subjects,
e.g.
handouts,
brochures,
flyers
and
advertisements.
The
following
materials
will
be
used
to
aid
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R&D Service (151)
recruitment
(after
appropriate
approval
from
the CMCVAMC
-IRB):
recruitment
flyer;
craigslist advertisement; clinician flyer.
9.
Informed Consent
9.1.
Informed Consent will not be sought. □
9.2.
Written informed consent from participants (VA Form 10-1086 is attached). Kl
9.3.
Written informed consent from participants' legally authorized representative (LAR) as
required by VA policy and/or applicable state laws (VA Form 10-1086 is attached). □
9.4.
Request Waiver of Documentation of Informed Consent □
9.5.
List the title of the key personnel involved in the following activities:
9.5.1.
Person Obtaining Consent
9.5.1.1.
Provide the title(s) of individual(s).
Principal
investigator,
study
coordinator,
behavioral
sleep
medicine
practitioners
associated
with this study
9.5.1.2.
Type
of
training
received
to
perform
this
process.
All
the
training on topics required by the Philadelphia Institutional Review
Board
(IRB)
prior
to
conducting
an
informed
consent
session
(including the CITI training for good clinical practices).
9.5.2.
Pre-Recruitment
Screening
(the
use
of
medical
records
and
other
data
bases
to
determine
populations
and
individuals
eligible
for
the
study),
Principal
investigator,
study
coordinator,
behavioral
sleep
medicine
practitioners
associated
with
this
study,
after
appropriate
authorizations.
Personnel
involved
will
include
the
following:
Principal
investigator,
study
coordinator, behavioral sleep medicine practitioners associated with the study.
9.5.3.
Recruitment Process
(the
process
in
which
individuals
are
contacted
and
first introduced to the study and to the possibility of participating as subjects),
Veterans
will
be
solicited
through
referral
from
treatment
providers
(ARU,
inpatient
unit,
primary care
providers,
providers
at the CBOCs
affiliated with
CMCVAMC,
case
managers
at
the
veteran
housing
support
programs
affiliated
with
the CMCVAMC
(IMPACT,
Fresh
Start,
Snyder
House,
VMC),
referrals
after
initial
assessment
by
the
Behavioral
Health
Laboratory,
and
self-referrals
(in
response
to
IRB-approved
advertisements)
posted
in
the
medical center and other areas like veteran housing support programs,
in the
electronic
media
(Craigslist).
Personnel
involved
will
include
the
following:
Principal
investigator,
study
coordinator,
behavioral
sleep
medicine
practitioners associated with this study.
"BHL conducts clinical assessments on all patients referred from primary care.
At the completion of the clinical assessment,
all patients potentially eligible for
IRB
approved
and
MIRECC
approved
research
will
be
informed
of
these
projects and asked
if they can be contacted by appropriate study personnel to
discuss the particular study in accordance to that protocol's procedures."
9.5.4.
Informed Consent Process (the process by which recruited subjects are fully
informed about participating
in the study and then formally give their voluntary
consent
for
participating).
Personnel
involved
will
include
the
following:
Principal
investigator,
study
coordinator,
behavioral
sleep
medicine
practitioners associated with this study.
9.5.5.
Screening of Recruited Subjects (those activities in the protocol
in which a
final determination of eligibility of prospective subjects is made during the
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early phases of the study, using laboratory data, inclusion and exclusion
criteria, and other person-specific information). Personnel involved will include
the following:
Principal investigator, study coordinator, behavioral sleep
medicine practitioners associated with this study.
9.5.6.
Include the breakdown of each individual's responsibilities:
9.5.6.1.
Principal Investigator. He may fulfill any of the roles required for
the
study,
including,
answering
questions
for
prospective
participants,
informed
consent
procedure
for
participation
for
assessment for study entry,
baseline assessments,
assessments
as
part
of
the
study
visits,
conducting
the
cognitive
behavioral
therapy sessions,
scheduling the participant sessions,
post-study
assessments,
conducting
the
urine drug
screens,
drawing
blood
and
preparing
the
blood
sample
for
storage
in
the
freezer,
coordinating clinical care with other providers.
9.5.6.2.
Co-Principal Investigator, N/A
9.5.6.3.
Research
Coordinator.
S/he
will
be
involved
in
answering
questions
for
prospective
participants,
informed
consent
procedure
for
participation
for
assessment
for
study
entry,
baseline
assessments,
assessments
as
part
of the
study
visits
including
the
urine
drug
screen
test
at
baseline,
drawing
blood
samples (after completion of the requisite training), scheduling the
participant sessions, post-study assessments.
9.5.6.4.
Additional
research
staff
by
title,
a.
Phlebotomy -
either
Dr.
Chakravorty
or a
designated
staff
certified
and
IRB-approved
to
draw blood will conduct the blood draws and prepare the samples
for the storage
in the designated R&D freezer space;
b. Certified
Behavioral Sleep Medicine
Provider:
s/he will conduct the CBT-I
and
the
QDT
sessions
for
the
participants;
the
Principal
Investigator,
Dr.
Chakravorty
will
conduct
CBT-I
or QDT
as
a
backup provider.
9.6.
Will informed consent be obtained from potential subjects prior to determining eligibility?
KlYES
[ZlNO
DN/A
9.6.1.
If no, provide justification and a HIPAA Waiver of Individual Authorization for
Disclosure of Protected Health Information.
9.7.
Define when a subject
is enrolled
into the study,
e.g.
after the subject signs the
informed consent or after randomized
to treatment.
After he
is
randomized
into
a
treatment arm.
9.8.
Describe:
9.8.1.
The
process when
informed
consent
will
be
obtained
and
protecting
patients'
privacy. The
principal
investigator or the trained research
staff will
schedule
a
session
with
the
prospective
participant.
In
this
session
the
prospective
participant
will
be
explained
about the
research
study
in
details
along with the associated
risks
including discomfort with the use
of portable
sleep monitor or elaborating on his past history of alcohol dependence as well
as
the
benefits
from
the
study
as
well
as
the
other treatment
alternatives
available.
On
comprehending
and
after
been
given
the
chance
to
ask
questions
related
to
the
study,
the
participant
will
complete
the
informed
consent quiz and then subsequently sign the informed consent document.
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T:ii<s!i;iVitflHi*/ A '..(s)Jiftfe
,;i«U-
recorded
after
the
participant
consents
to
the
data
collection;
data
will
be
collected in a private room in the office space of the MIRECC on the 2nd floor,
or the mental
health
clinic,
or the addiction
recovery
unit,
or
in the
inpatient
units
of CMCVAMC. The source documents
or the case
report form
will be
stored
in
the
locked
cabinet
in
room
number 228
B
of the MIRECC
office
space or in the locked cabinet in room (TBA)in CMCVAMC, depending on the
available space.
All the data
will
be entered
into password
protected
online
servers,
using the 4-digit
identification number issued
to the
subject.
All the
personal
identifiers
as
identified
by
HIPAA
will
be
removed
from
the
data
spreadsheets.
The
portable
sleep
study
data
will
be
downloaded
in
the
CMCVAMC sleep center or
in the MIRECC
office spaces and the
final data
will
be downloaded
onto
a
disk and transported
physically
by the
research
staff
to
the
MIRECC
storage
area
and
uploaded
to
the
online
servers.
Actigraph
data
will
be downloaded
onto the
specific software
that
currently
exists on one personal computer
in
Dr.
Chakravorty's
office
in Room # 218,
Bldg
3,
and
the
password
protected
desktop
computer
of
the
principal
investigator
in
the
locked
room,
room # 218
of
building
3,
a
building
with
restricted
entry.
In
addition,
a
backup
copy
of
the
actigraph
data
will
be
maintained
on
compact
disks,
as
recommended
by the
manufacturer,
in
a
locked cabinet of the principal investigator's office. All the discs will be stored
in
the
principal
investigators
locked
office
in
Room # 218
of the
research
building with restricted access, in a locked cabinet.
9.8.2.
Any waiting
period
between
informing
the
prospective
participant and
obtaining consent. The waiting
period
will
be dictated by the
availability of
the Veteran and the staff member's availability
in going through the informed
consent session.
9.8.3.
Steps taken to minimize the possibility of coercion or undue influence.
The subjects will be reminded of the voluntary nature of the study during the
initial screening, during the informed consent session, as well as tested
in the
informed consent quiz.
9.9.
Provide the language
9.9.1.
Used by those obtaining consent. English
9.9.2
Understood
by
the
prospective
participant
or
the
legally
authorized
representative. N/A
9.10.
Provide location where informed consent will be obtained. The informed c°nsent
session will be conducted in any available private office space available on the 7th or 2n
floor (mental health clinic/ARU clinic), MIRECC office spaces (room # 228), the inpatient
units on the 7th floor, or in any available office space in the primary care clinics.
10.
Waiver
or
Alteration
of
Informed
Consent
Requirements/Waiver
of
Requirement
to
Obtain Documentation of Informed Consent
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10.1.
Are you requesting a waiver or alteration of informed consent? (Check all that apply)
10.1.1.
NoD
10.1.2.
Yes; provide justification. □
10.1.3.
Yes; for recruitment purposes only.
Kl
10.1.3.1.
An
IRB
may
approve
a
consent
procedure
which
does
not
include, or which alters, some or all of the elements of informed
consent
set
forth
in
this
section,
or
waive
the
requirements
to
obtain
informed
consent
provided
the
IRB
finds
and
documents
that:
•
Kl
1. The research
involves no more than minimal
risk to the
subjects;
•
[x]
2.
The
waiver
or
alteration
will
not
adversely
affect
the
rights and welfare of the subjects;
•
|EI 3. The research could not practicably be carried out without
the waiver or alteration; and
•
IEl
4.
Whenever
appropriate,
the
subjects
will
be
provided
with additional pertinent information after participation
•
□
5.
The
research
or
demonstration
project
is
to
be
conducted
by
or
subject
to
the
approval
of
state
or
local
government
officials
and
is
designed
to
study,
evaluate,
or
otherwise examine:
a.
Public benefit or service programs;
b.
Procedures
for
obtaining
benefits
or
services
under
those programs;
c.
Possible changes
in or alternatives to those programs or
procedures; or
d.
Possible
changes
in
methods
or
levels
of payment
for
benefits or services under those programs.
10.2.
Are you requesting a waiver to obtain documentation of informed consent?
10.2.1.
NoKI
10.2.2.
Yes; provide justification. □
10.2.2.1.
An
IRB
mav
waive
the
requirement
for
the
investigator
to
obtain a signed consent form for some or all
subjects
if
it finds
either:
•
□
1. That the only record linking the subject and the research
would be the consent document and the
principal
risk would
be
potential
harm
resulting
from
a
breach
of
confidentiality.
Each
subject
will
be
asked
whether
the
subject
wants
documentation
linking
the
subject with
the
research,
and the
subject's wishes will govern; or
•
□2. That the research presents no more than minimal risk of
harm to subjects and involves no procedures for which written
consent is normally required outside of the research context.
R.
Compensation
1.
Summarize any financial compensation that will be offered to subjects.
Please see Table
3
below for details on the financial compensation.
2.
Provide the schedule for compensation. The schedule
of pro-rated
compensation
will
involve
one payment for completion of the baseline assessments measures, weekly compensation for the
each of the study visits over 8 weeks, and for the 2 post-study visits at 3 months and 6 months.
2.1.
Per study visit or session. The specific details of the payments are shown in Table 3
2.2.
Total amount for entire participation. $750.
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3.
4.
5.
Explain how compensation will be provided via cash, voucher, gift card, etc.
Patient will be
given a voucher that may be exchanged for cash
at the agent cashier of CMCVAMC,
similar to
that done for prior studies.
If financial compensation will be prorated, explain the process. See Table 3 below for details.
Not Applicable - □
Table 3: Suggested Pro-rated Financial Compensation Involved with
Missing
Assessments
None
Incomplete Actigraphy
Incomplete forms
> 2 Ratinq Scales
Polysomnogram
Any combination of above
No blood sample
Baseline
Assessments
$150
$125
$125
$125
$100
$50
$100
Week
1-7
$50
$25
$25
$20
-
$15
-
Week
8
$100
$75
$75
$70
$50
$15
-
F/U
(in3&6
months)
$75
$40
$50
$40
-
$40
-
S.
Withdrawal/Early Withdrawal
1.
Describe
how
and
when
a
subject
may
withdrawal
from
the
study.
Once
the
subject
completes
the
first
session
of the
CBT-I,
he
will
not
be
dropped
from
the
study,
unless
they
specifically request that they not be contacted, or the subject cannot be located for assessment by
the 8-week follow-up. The subject may voluntarily withdraw from the study
at any
point
in time.
Subjects who are discontinued from the cognitive behavioral therapy intervention
will continue to
be followed
in the
study
until the
completion
of the
8 weeks
of intervention and the
post-study
follow-up
at
3
and
6
months. The
reason
the
subject
is
discontinued
from
the
study and
any
referrals that are made are documented in the appropriate section of the subject's casebooks.
2.
Provide procedures for the orderly termination of participation by the participant and
if any
consequences
would
result from
early
withdrawal
from
the
study.
The
subject
may
be
terminated from the research study by the investigator, without regard to
his/her consent,
under
certain
conditions.
These
conditions
may
include,
if
s/he
does
not
comply
with
the
recommendations of the research staff, including compliance with study related procedures on >3
consecutive
office appointments;
s/he
reports ideas of harm
to
self or to anybody else with any
intent and/or a
plan. S/he will additionally be referred to the outpatient treatment program
at the
Addiction Recovery Unit of the CMCVAMC. Alternatively patient will be withdrawn from the study
on successful completion of their study participation.
Subjects will be discontinued/withdrawn from the study
if any of the following events occur:
•
Any condition which the study psychiatrist finds CBT-I to be a hazard to the subject
(i.e.
patient seen
to
be
agitated,
onset
of increasing
paranoia,
inability
to follow
through with recommendations and/or homework)
•
Participant screens
positive
at baseline for moderate to severe
obstructive sleep
apnea
(as seen baseline screening
portable sleep monitor data), and
is currently
on not treatment for the obstructive sleep apnea
•
Relapse to sustained heavy drinking during treatment as quantified at > 5 standard
drinks for men and > 4 standard drinks for women less than 70 years of age, or a
total
of 14 drinks/ week
in men and
7 drinks
per week
in women
for >4 days a
week and >1 week;
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•
Development
of an
inter-current medical
illness
or condition
that
requires
a new
hospital admission
•
Emergence
of
another
substance
abuse
problem
which
necessitates
inpatient
admission or a more aggressive treatment than provided by the protocol.
•
Subject is incarcerated for more than a week.
Study participation can be restarted after consultation with the research physician for subjects
who 1) return to treatment after a period of brief absence of less than 3 weeks, or 2) return to
treatment after brief inpatient hospitalization of less than 2 weeks or additional outpatient-
treatment.
Restarting study procedures is contingent upon clinical need and continuing to meet
inclusion and exclusion criteria.
3.
Explain if survival data is required.
If so, clarify how data will be obtained. We will not be
assessing for survival data in this pilot study. However we may consider looking at the survival
data
if there are a significant number of drop out of subjects from the study, with the end point of
the survival analysis being the drop out date (i.e. total duration of participation in the study).
4.
Not Applicable; subjects not recruited; chart review. □
T.
Risk/Benefit Assessment
1.
Potential Study Risks
1.1.
Describe and assess all of the following risks that may be associated with the research:
1.1.1.
Physical a. Portable Sleep Apnea Monitoring: there may be discomfort
associated with the use of nasal cannulas and sensors on the chest/abdomen;
b. Overnight Polysomnography: Sleeping
in the CMCVAMC sleep laboratory
with adhesive leads on the body may be associated with physical discomfort;
1.1.2.
Psychological a. Sleep Restriction: patients may experience an increase in the
daytime sequelae of insomnia as a result of this intervention (the scheduling of
time in bed so as to equal average total sleep time).
In the first few days of
treatment this is likely to entail some sleep deprivation (~1
hour less sleep than
is normal for the individual) and result in a transient increase in daytime
sleepiness, fatigue, concentration problems, and irritability;
b. Data Collection
during the Study: there may be discomfort associated with talking about family
history of alcoholism, psychiatric issues and addiction-related issues.
Furthermore,
in some cases, the use of the sleep diaries and actigraphs may
lead to (or be perceived as causing) a transient worsening of insomnia
symptoms at home; c. Relapse to Alcohol: there is a possibility that the
transient "side effects" of CBT-I may lead some individuals to resort to
occasional alcohol use and that such behavior may also lead to relapse (heavy
drinking); d. Use of Other Drugs: there is a possibility that the transient "side
effects" of CBT-I may lead some individuals to start using other drugs while
taking part in the study-related procedures; e. Suicidal/Homicidal Ideation.
While there is no evidence that CBT-I increases suicidal or homicidal ideation,
it is a possible consequence of the transient sleep deprivation that occurs with
CBT-I. That is, sleep deprivation may lead to decreased inhibition in the frontal
brain areas, which may,
in turn, lead to a failure to inhibit or cope with such
thoughts, especially in vulnerable populations like those who suffer from
alcoholism.
1.1.3.
Social. A decreased interest in affiliating with other people because of
persisting insomnia or a transient increase in the insomnia secondary to the
sleep restriction associated with the CBT-I.
1.1.4.
Economic. Time spent participating
in the study may interfere with the subject's
ability to seek employment or participate at his job.
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1.1.5.
Monetary. May be secondary to loss of time spent in participating
in the study.
1.1.6.
Legal. An increase in the drowsiness may lead to potential risk of a motor
vehicle accident.
1.1.7.
Loss of confidentiality a. there is a possibility that the subject's identifying data
and/or study information may be viewed by non-study personnel.
1.1.8.
Assess the likelihood and seriousness of such risks. Although the risks
associated with drowsy driving are serious, the likelihood of this risk is low. The
likelihood of the other risks are variable, between a low to a moderate level,
and specific to the Veteran's individual situation.
1.1.9.
Other. N/A
1.2.
Specify what steps will be taken to minimize these risks.
a.
Portable
Sleep
Apnea
Monitoring:
While
the
use
of
nasal
cannulas
and
sensors
on
the
stomach
and
abdomen
are
required
for
this
screening,
subjects
that
experience
discomfort
during
orientation
will
be
provided
(where
possible)
the
opportunity
to
select from different types of cannulas and sensors
.
c.
Sleep
Restriction:
As
noted
above,
this
behavioral
procedure
is
not
without
side
effects
(sleep
loss
and
increases
in
the
daytime
symptoms
of
sleepiness,
fatigue,
concentration problems, and
irritability). The subject
will be made aware that "things
will
[and
must] get worse
before they get better" and that the transient worsening
of
symptoms
is
in the service of long-term gains. This said,
in the rare cases where the
procedure
is viewed by the
patient as
intolerable, the
protocol
will be to either
1)
re
assess the patient's basal sleep ability (conduct a second baseline assessment) or to
substitute sleep compression54 for sleep restriction.
In addition,
similar to our clinical
care,
we
will
counsel
and
monitor
subjects
at
each
of
the
follow-up
visits
for
any
excessive
daytime
drowsiness
leading
to
drowsy
driving,
a
risk
factor
for
a
motor
vehicle
accident,
and we
will
review tips to avoid drowsy driving.
If the
patient does
not
wish
to
engage
in
these
alternatives
or
the
accommodations
above
do
not
increase
the
tolerability
of the
intervention,
then
the
subject
is
(as
always)
free
to
withdraw from the study.
d.
Data
Collection
during
Initial
Evaluation.
Every
attempt
will
be
made
to
minimize
the
discomfort
associated
with
disclosure
of
personal
data.
All
of
our
staff
are
accustomed
to
and
have
a
high
degree
of
facility
with
the
acquisition
of
sensitive
information
(e.g.,
drinking
history).
If,
despite
our
staff's
best
efforts,
the
patient
is
unable to discuss issues that bear on their family and/or clinical history, they are free
to not disclose this information and they are free to withdraw from the study.
Further,
if the
patient's
reluctance to share
information
precludes the acquisition
of data that
are
critical
to the conduct
of the
study,
they
will,
at the
Pi's
discretion,
be asked
to
withdraw
from
the
study.
In
the
event
that
the
subject
feels
they
cannot
tolerate
completing
daily sleep
diaries
or wearing
the
study
actigraph,
they
will
be
told
that
such effects tend to be very transient.
If the subject continues to find the collection of
such
data
intolerable
and/or
is
non-compliant,
they
will
initially
be
assisted
by
the
study-related
staff
in
being
compliant
with
the
data
collection
through
frequent
reminders (as these data are central to the study). Despite frequent reminders,
if they
continue
to
remain
non-compliant and
at the
Pi's
discretion,
they may
be
asked
to
withdraw from the study.
e.
Confidentiality:
During
the
participation
in
this
study,
the
patient
will
be
assigned
a
4-digit
unique
identification
number.
This number
will
not be
derived
from
PHI
of any
sort
(e.g.,
DOB,
SSN,
etc.)
and
will
simply
represent
the
study
and
the
subject's
recruitment number (e.g.,
1001). Study numbers will be linked to subject identifiers
in
one spreadsheet that
will be stored on the
Pi's password-protected VA online
drive.
These
efforts
make
it
very
unlikely
that
the
subject's
identifying
data
and/or
study
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information may be viewed
by non-study
personnel. The data
will now be captured
and stored within the VA Redcap and stored in the secured VA servers.
f.
Relapse
to
the
Drinking.
All
drinking
behavior
will
be
monitored.
Monitoring
will
be
based
upon self-report items on the daily sleep diaries and clinical interviews by the principal
investigator during
the
outpatient
visits.
These
variables
will
be
monitored
for
both
research and
clinical
purposes. The
research
purpose
is
to
determine how alcohol
use varies with treatment for insomnia. The clinical purpose is to be able to determine
if there has been
a
resumption
of heavy
drinking
(four standard
alcoholic drinks on
any day or > 14 drinks a week).
If there
is a resumption of sustained heavy drinking
and this sustained heavy drinking places the subject at risk of medical, psychological
or physical harm, then he will be withdrawn from the study, and a referral to the ARU
or the inpatient unit, as deemed necessary for further treatment,
will be offered to the
participant
g.
Use
of
Other
Street
Drugs.
Patients
will
be
evaluated
for
the
use
of
other
street
drugs
through
structured
assessment
instruments.
Further,
if there
is
a
history
of
regular
drug
use, the subject will be regularly monitored with standard
urine tests
(note:
this
will be a condition for admittance
into the study).
If regular drug use
is detected, the
subject
will
be
withdrawn
from
the
study,
and
a
referral
to
the
ARU
for
further
treatment will be offered to the participant.
h.
Suicidal/Homicidal
Ideation.
If
the
participant
reports
suicidal
ideation
with
intent
to
hurt
themself,
or
if on evaluation,
s/he
is seen to be a danger to themself or others,
s/he
will
be
referred
immediately
from
the
office
to
the
Emergency
Department
of
the
CMCVAMC (CMCVAMC
-ER).
If s/he
reports
passive
suicidal
ideation,
s/he
will
be
monitored
for
any
change
during
visits.
S/he
will
also
be
offered
a
referral
to
the
Addiction
Recovery
Unit
of the CMCVAMC
for further evaluation
at the
end
of the
study.
1.3.
If methods of research create potential risks, describe other methods,
if any, that
were considered and why they will not be used.
In the extreme situation where the
risks cannot be mitigated with the above steps, and risk of participation
in the study are
considered to be greater than
non-participation, the
P.I. may withdraw the subject from
the
study
and
monitor
him
till
the
end
of
the
study
duration,
along
with
any
other
additional clinical care that may be warranted.
1.4.
If chart review, breach of confidentiality is always a concern.
Specify what steps
will be taken to minimize these
risks. These
will
include the following:
restriction
of
chart review to the
P.I. and the study coordinator;
storing the identifying
information
in
locked
drawers
in
locked
office
spaces;
use
of
any
of
the
17-HIPAAA
identifiers
to
communicate
with
research
staff either over the phone
or
using
the
"do
not forward"
option
of the VA email system;
and
discarding the
patient
related
information
into the
designated shredding
bins within the VA promptly
after the
information
is reviewed
or
communicated with staff or the specific Veteran.
2.
Potential Study Benefits
2.1.
Assess the
potential
benefits to be gained
by the
individual
subject,
as well as
benefits that may accrue to society in general as a result of the planned work.
It is
possible
that
the
patients
will
not
obtain
any
benefit from
participation
in
this
study.
However,
it
is also possible that some of the participants may have an improvement
in
their
insomnia
after
completion
of
their
participation
in
the
study.
Some
potential
participants who screen positive for moderate to severe obstructive sleep apnea will be
referred
to
the CMCVAMC
Sleep
Center
for further evaluation
and
treatment
for the
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disorder.
In addition, as seen in our past Quetiapine Sleep Study and our current CBT-I
pilot
study
in
the
recovering
alcoholics,
some
of
the
subjects,
by
virtue
of
their
participation
in
this
study,
may
obtain
a
better understanding
of their insomnia
and
available treatments after the end
of the study. This understanding
will therefore help
them make better choices for their future insomnia treatment.
3.
Alternate Procedures
3.1
Describe the
alternatives
available to the subject outside the
research
context.
Alternatives
available to the
participant include the following:
to
not
participate
in the
research study at
all, taking a sedating
psychotropic medication for their insomnia as
prescribed
by
the
patient's
care
provider,
or
enrolling
for
CBT-I
treatment
at
the
CMCVAMC sleep center.
U.
Data and Safety Monitoring Board (DSMB) or Data Monitoring Committee (DMC)
1
Will an independent DSMB or DMC oversee the project?
IEIYES
DNO
UN/A
1.1.
If yes, please provide contact information for the DSMB or DMC or Coordinating Center
Representative and attach a copy of the charter.
Name:
Tamara Paine
Phone Number:
708-202-5785
Title:
Project Manager
E-mail:
Tamara.Paine@va.gov
2.
If a DSMB or DMC will not monitor this study, who will monitor this study? Check all that
apply.
□Principal Investigator
□Sponsor
□VA Cooperative Studies Program
□Safety monitoring committee
V.
Data Monitoring
1.
Describe the data monitoring
plan. A
monitor,
independent of the study team
will
regularly
inspect the accuracy of data entered. S/he
will randomly pick out the source documents and
ensuring that the study is adhering to the study protocol with the applicable research regulations
and CMCVAMC requirements.
2
Describe how protocol deviations, adverse events, serious adverse events, breaches of
confidentiality,
unanticipated
adverse
device
effect
(UADE),
and
unanticipated
or
unexpected
problems
will
be
reported
to
the CMCVAMC
IRB
and
sponsor.
Protocol
deviations, adverse events, and unanticipated/unexpected problems will be notified in writing to
the CMCVAMC IRB as per CMCVAMC R&D regulations and to the DMC.
Serious adverse
events and unanticipated adverse events will be reported to the IRB within 5 days of knowledge
of the event. Adverse events will be reported in the continuing review as per regulations.
2.1.
Describe the management of information obtained that might be relevant to participant
protections such as:
2.1.1.
Unanticipated
problems
involving
risks
to
subjects
or
others.
The
unanticipated
problems
involving
risks
to
the
subjects
or
the
others
will
be
notified to the CMCVAMC -IRB.
In addition, subjects will be individually notified
of
the
unanticipated
problems
and
the
associated
risks
and
benefits
of
continued
participation
will be furnished - this
will
help the Veteran make an
informed decision on the need for continued participation.
2.1.2.
Interim results. N/A.
2
1 3
Protocol modifications. The protocol modifications will be implemented after
authorization from the CMCVAMC -IRB. Where ever applicable, the subject will
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need
to sign an
updated consent form,
if the changes
in the
protocol
involve
him
and
occur
while
he
is
participating
in
the
research
study-related
procedures.
3.
If applicable, define the plan for subjects if research shows results such as:
3.1.
Depression
- depressive symptoms are common
in those complaining
of insomnia as
well
in Veterans during early recovery. Depressive symptoms will be monitored through
the study.
3.2.
Suicide
-
In the unusual situation the participant
is seen to develop severe depressive
disorder with
inability to function with
his daily
activities or seen to have the onset of
suicidal
ideation
with
intent
and/or
plan,
the
veteran
patient
will
be
referred
to
the
CMCVAMC - ER for further evaluation and treatment.
3.3.
Abuse -
If participant
is seen to abuse another drug excluding cannabis and
nicotine
through
the
study,
s/he
will
be
monitored
and
at the end
of the
study,
s/he
will
be
recommended a referral back to the ARU.
If s/he
is currently in treatment in the ARU,
her/his treatment team will be notified of the clinical progress
in the research study as
well as the new substance use.
In case the patient is discovered to have dependence to
another drug
e.g.
a
sedative-hypnotic
or
opiates
s/he
will
be
monitored
through
the
active study and follow up, educated about her/his drug dependence,
urged to abstain
from the drug use and
if s/he consents, referred to the ARU for active treatment and will
also be simultaneously follow up by our research
staff,
till the end of the study related
follow up visits.
4.
Statistical Analysis
4.1.
Include statistical power calculations and the assumptions made in making these
calculations. The following power calculations for Aims
1-3 assume the availability of
86 subjects who are eligible for randomization into one of two groups (n=43 per group).
We
assume
a
range
of
intra-class
correlation
of
0.1-0.5
and
up
to
10
follow-up
measures per participant. The sample size is inflated to accommodate a 30% missing or
dropout
rate
by
6
months
based
on
rates
over
a
similar
period
of time
in
previous
studies55. We consider a conservative adjustment in the two-sided level of significance,
0.025,
to
account for two
hypothesis
tests
per Aim
(3-month
and 6-month
outcome).
Table 4 presents the detectable effect size based on the above assumptions for 90%
and 80%
power.
The study will have 80% power to detect a moderate effect size
of
0.50 standard deviations of a continuous outcome measure
at 6 months assuming an
intra-class correlation of 0.3. Table 5 presents the detectable effect in units applicable to
each outcome based on the observed standard deviation from studies in the literature.
Power
80%
90%
sffiWBaanaani
Intra-class
Correlation
0.1
0.3
0.5
0.1
0.3
0.5
Detectable effect size
3 months
0.35
0.48
0.58
0.40
0.55
0.66
6 months
0.40
0.50
0.61
0.41
0.57
0.70
(Assumptions: power=80%; n=30 per group
after,30°/d,attrition;2-sided=0.05)
• Standard Deviation
"Insomnia Se
c Quality of Life
' Pooled within group standard deviation
•
Pooled
within
group
standard
deviation
(estimated from presented data)
f Pooled within group standard deviation for
general health
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Outcome
1ST
Abstinent Days
d
Health Related
Pre-Post
S.D."
3.809u
15.96e
9.157
Detectable
Difference
1.90 points
7.98 %
4.58 points
4.2.
Define
plans
for
data
and
statistical
analysis,
including
key
elements
of
the
statistical
plan,
stopping
rules
and
endpoints.
Overview:
Our
study
proposes
a
longitudinal
repeated-measures
parallel-group
design.
This
powerful
design,
with
a
baseline measurement and up to ten follow-up measures per participant over 6 months,
allows for comparisons within each participant over time as well as across participants
(treatment
groups).
The
main
analysis
will
look
at
differences
between
intervention
groups in the changes in outcomes over time
(i.e. insomnia severity, alcoholism-related
outcomes
and
daily
functioning).
Randomization:
Patients
will
be
recruited
and
randomized
as
individuals
Allocation
will
be
uniform
across
the
two
groups
after
suitable
blockingsaQ^stratiGcatlori^on
family&tfislp/y.Vof alcoholism
to
ensure: optimal
balance ofpjpaKj£b|jp^
9rouPs with
and;witho\i1t1s9aW^
Participants
are
randomly assignedto the CBT-I group,
or the QDT group. The study biostatistician
will
create randomization sequences by family history of alcoholism
(separate sequences)
using
a
pseudo-random
number
generator
with
block
sizes
of
4.
Two
boxes
of
sequentially
numbered,
sealed,
opaque
envelopes
will
be
prepared
using
the
randomization sequences and labeled "Family History" and "No Family History". At the
time
of
randomization,
the
first
envelope,
in
sequential
order,
is
pulled
from
the
appropriate box and opened
to
reveal the group assignment.
All
the
staff conducting
assessments will be blinded to the allocation of treatment arm with the exception of Dr.
Findley,
the
BSM
treatment
provider,
Ms.
Barilla
the
person
overseeing
treatment
allocation,
and
Dr.
Harb,
the
monitor
for
BSM
treatment
for
the
study.
Preliminary
Analyses:
All
data,
regardless
of the format,
will
first be assessed by
Dr.
Chakravorty
and
his mentors for missing
data,
distributions
of
all observed
measures,
and
out-of-
range values by means of conventional descriptive tables. SAS v9.3 will be our primary
tool for these analyses as the software is both mature and well-documented56. Next, we
will employ raw and smoothed plots to visualize the individual and average trajectories
of all repeated measures over time according to assigned treatment and by participant
characteristics. All questions of data quality and integrity will be investigated before any
statistical
modeling,
since
complete
and
accurate
data
are
essential
for
unbiased
estimates
and
confidence
intervals.
We
will
compare
all
baseline
variables
across
groups
to
check
the
adequacy
of
randomization.
The
baseline
comparisons
will
be
based
on:
1)
t-test or Wilcoxon rank sum tests for continuous variables depending on
the symmetry of the distributions; 2) on logistic regression for binary or ordinal variables;
and
3)
on
Poisson
log-linear
regression
for
count
data.
If
imbalances
are
found
at
baseline, then the relevant variables will be treated as confounders in the analysis.
Specific Aims
1-3: The analysis for the
specific aims
1-3
is based upon the
intent-to-
treat principle;
all randomized participants will be included
in the analysis regardless of
whether
they
drop
out
of
the
intervention
or
study.
The
analysis
will
involve
the
comparison
of the
insomnia
severity
(Aim
1),
abstinence from
drinking
(Aim
2),
and
quality
of
life
(Aim
3)
across
the
intervention
groups
in
order
to
allow
for
different
trajectories of the outcome measures and to afford flexibility
in making contrasts within
participants
over
time
and
across
participants
while
simultaneously
controlling
for
potential confounding factors, we propose the participant-specific or mixed effects linear
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model.
In this model, the mean ISI depends on fixed covariates and random effects 57.
The .'fixed .cgVaijaJ,eg:^f jr|ejcest?jpclude
time,
treatment
assigrjngiejit,
thejntenpction
between tirKe^hdWeatmeB^si^nhient,' adjustjh^fbr fa'mily history^of alcoholism' and
confounding. yariables
• iden,W[ed
in
the
preliminary 'analysis.. The
random'effects
represent the "unobserved factbVs that lead td'variation
of the
individual
participant's
qutcgme.
Random
intercepts
for each
participant
permit modeling
of
natural
variation
across participants at baseline
in the outcome of interest.
In addition, random slopes or
random effects for the trajectory of each participant over time allow for variation of each
participant
about
a
mean,
overall
trajectory
across
all
participants.
Estimates
of
the
random effect for an individual participant also permit far more focused investigations of
those
individuals who depart from the mean over time and experience
either better or
worse
than
average
change
in
outcome.
Thus,
the
mixed
effects
longitudinal
model
permits
both comparisons
of groups
as well
as
contrasts
of individuals.
Although
less
robust to model
misspecification, the mixed
effects paradigm
offers special
flexibility
in
longitudinal data when exposures vary over time and when
dropout and
missed
visits
lead
to
unbalanced
groups.
ISI
and
quality
of
life
are
continuous measures and
most
likely
follow
a
symmetric
or
approximately
normal
distribution.
Therefore
the
linear
mixed
regression model
is appropriate.
If departures from
normality are found, we
will
consider transformations
or other distributional forms that may
better
fit the data. The
alcoholism-related
outcome
measures
are
counts
(e.g.
number
of
days
abstinent,
number
of
heavy
drinking
days,
etc.)
but
will
be
summarized
as
percentages
(e.g.
percent abstinent days) and
will also most likely follow a normal distribution. The target
of inference
is the
participant-specific response to treatment over time.
Specifically we
are interested in the efficacy at the end of treatment (8 weeks) and durability after 3 and
6
months
of follow-up.
At each
time
point
of
interest, we
will
estimate from
the
fitted
model the difference from baseline in the outcome for each treatment group and test the
difference
between
these
differences.
The treatment
effects
will
be
the
contrasts
that
represent
the
difference
of
differences
from
baseline
in
outcome
across
treatment
groups
at 3 and 6 months.
Both
univariate and
multivariate
results
will
be
reported
in
terms of Wald test, point estimates, and 95% confidence intervals.
Exploratory Aim
4: We
will
examine whether family
history
of alcoholism
modifies the
effect
of
the
intervention
on
outcomes.
Effect
modification
or
moderators
of
the
intervention
will
be
tested
and
estimated
with
3-
and
2-way
interactions
among
the
treatment
factor,
potential
moderator,
and
time
in
the
ITT
models
described
above.
Because the hypotheses
relating
to
effect
modification
will
be
exploratory, we
will use
p=0.1
to
declare
significance
of such
interactions.
The
analyses
will
be followed
with
stratified analyses corresponding to the effect modification hypotheses.
Regarding
missing
data and
drop-out, we
will
assess the
relationship
of missing
data
patterns
with
dependent
and
independent
variables.
Specifically,
we
will
use
logistic
regression
with
missingness
as
the
binary outcome and
dependent and
independent
variables
under
each
Aim
as
covariates
for
the
missing
data
model.
If
there
are
significant associations, we will perform multiple imputations with PROC Ml
in SAS, and
take
weighted
averages
of
parameter
estimates
and
standard
errors
from
the
longitudinal regressions across the multiple imputation iterations.
W.
Privacy and Confidentiality
1.
Indicate the type of data that will be received by the Principal Investigator.
Check all that
apply.
1.1.
□De-identified - Without any identifiers that could link the data to a specific participant.
(Contact
Privacy
Officer
for
assistance.
If data
is
coded,
it
is
not
considered
de-
identified.)
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1.2.
1.3.
1.3.3
□
Identified
-
Linked
to
a
specific
participant
by
identifiers
sufficient
to
identify
participants.
(See HIPAA and Common Rule Criteria for list of identifiers.)
K) Coded - Linked to a specific subject by a code rather than a direct identifier.
If coded
is checked, specify:
1.3.1
Explain who will maintain the link or code. The principal investigator and the
research
assistant
will
have
access
to
the
codes,
which
will
be
stored
in
a
locked filing cabinet in room #228 or in the locked cabinet in Dr. Chakravorty's
office (TBA).
In
addition,
the code
will
also be stored
in a back~uP
file
in the
password
protected online drive of the
principal
investigator U the MIRECC
drive (\\vhaphifpcmirecc\Research Studies\Chakravortv - CBT-I) or the K: drive
of the PIA\vhaphiclunas11s (K:)^
1.3.2
Describe who will
have access to the
link or code.
P.I.,
and/or the study
coordinator.
Provide
exact
details
for how
the
data
is
coded.
J
iiinot
Room #218, Bldg 3
„_.
.
Jor the K: drive of the PIA\vhaphiclunas11s (K:)|
2.
Does the project require the use of existing Protected Health Information (PHI) from a
database, medical records, or research records?
IE1YES
QNO
QN/A
2.1.
If yes,
2.1.1.
Specify the source of the existing
PHI. The CMCVAMC medical records
in
CPRS.
2.1.2.
Indicate the specific data elements/identifiers (e.g., name, address, phone
numbers, etc.) on the below table. We will collect personal information such
as
name,
address
(street
address,
city,
county,
precinct,
ZIP
code),
dates
directly
related
to you
(including
birth
date,
admission
date,
discharge
date),
telephone number for you as well as for a designated contact person
(in case
we cannot contact you),
electronic mail address,
social
security number,
HIV
and
infectious
disease
diagnoses
results
and
treatment
records,
information
related to the diagnoses and treatments related alcohol and/or other drug use
disorder/s,
results
of
sleep
disorder
evaluation
and/or
any
sleep
related
studies,
any
radiological
studies,
prior
laboratory
tests
for
medical
disorders
(including
and
not
related
to
liver
function
tests,
thyroid
function
tests,
hyperlipidemia,
diabetes),
current medications, and the
results of prior history
and physical examinations.
2.2.
If the study uses an existing database/data warehouse,
2.2.1.
Provide a description of the database/data warehouse.
The patient's
clinical chart, CPRS will be used to prescreen subjects and subsequently we
will contact the Veterans' practitioner regarding the possibility of discussing this
study with the Veterans.
2.2.2.
Make clear who is responsible for maintaining
it. N/A
2.2.3.
Cite any relevant Standard Operating Procedures (SOP) for the
database/data warehouse.
N/A
2.2.4.
Provide a copy of the SOP.
3.
Will PHI be collected prior to obtaining informed consent?
[X]YES
□NO
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4.
HIPAA Identifiers - Indicate the PHI that will be collected from project participants directly or
indirectly.
4.1.
Kl Name
4.2.
[J3 All geographic subdivisions smaller than a State, including street address, city,
county, precinct, zip code, and their equivalent geocodes, except for the initial three
digits of a zip code
if, according to the current publicly available data from the Bureau of
the Census
4.3.
IE!
All elements of dates (except year) for dates directly related to an individual, and all
ages over 89 and all elements of dates (including year) indicative of such age, except
that such ages and elements may be aggregated into a single category of age 90 or
older.
4.3.1.
□Birth Date
□Date of Death
4.3.2.
□Discharge date
□Admission date
4.3.3.
□Appointment Dates
□Other Dates (e.g. lab tests, x-rays, MRI, etc.)
4.4.
IEI Telephone numbers
4.5.
□Fax numbers
4.6.
Kl Electronic mail addresses
4.7.
[El Social Security Number
4.8.
□Medical record numbers
4.9.
□Health plan beneficiary numbers
4.10.
□Account Numbers
4.11.
□Certificate/license numbers
4.12.
□Vehicle identifiers and serial numbers, including license plate numbers
4.13.
□Device identifiers and serial numbers
4.14.
□Web universal resource locators (URLS)
4.15.
□Internet protocol (IP) address numbers
4.16.
□Biometric identifiers, including fingerprints, voiceprints, audio recordings
4.17.
□Full-face photographic images and any comparable images
4.18.
□Any other unique identifying number, characteristic, or code
4.19.
IEI Personal and Family History
4.20.
£<] History and Physical Examination
[El Progress Notes
4 21.
|El Discharge Summary(ies)
□Photographs, videotapes, other
images
4.22.
□X-Ray
□HIV (testing or infectious disease) records
4.23.
[El Diagnostic/Laboratory tests
□Sickle cell anemia
4.24.
IE3 Drug Abuse Information
IEI Behavioral Health notes
4.25.
Kl Alcoholism or Alcohol Use
IEl Operative Reports
4.26.
□Billing records
[3 Medication List
4.27.
E3 Health Summary Reports
□Anatomic Pathology Report
4.28.
pother Records: Any prior sleep studies or treatment outside the VA health system for
sleep disorders
5
Will participants be contacted from existing PHI?
[ElYES
DNO
ON/A
5.1.
If yes, clearly explain how participants will be contacted. We will contact the prospective
participants who
have
been
identified
by
their
providers
after expressing
willingness
regarding the study or alternatively,
if the participant contacts us directly regarding the
study.
In addition, providers of patients identified by review of records will be contacted
by the study related staff to discuss the study briefly with the patients.
6.
Provide the
titles
of the
exact
individuals who
will
have access
to the
collected
data.
See
section 6.1
below for details.
6.1.
Explain why these individual will have access to this data.
1. The principal investigator - he may conduct any of the procedures, as may be necessary
2. Research Assistant - coordinate the study related visits and procedures.
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3. Psychologist associated with the study (Certified Behavioral Sleep Medicine Specialist, TBA)
- to assess, and answer any questions that the participant may have, especially
if he
is non-
compliant with a study related visit.
4. The regulatory agencies including the IRB at the CMCVAMC, DMC, and the grant funding
organization VA CS R & D. They will have access to the information
in order to conduct their
regulatory activities.
5. The genetic data will be stored
in the freezer space designated by the CMCVAMC R&D
services and will reside there with the coded
identification numbers and without any of the 17
HIPAA identifiers. Once
all the samples have been collected and we are ready to commence
the genetic analyses, we will request CMCVAMC -IRB approval to transfer the blood samples
to
the
designated
laboratory
at
the
University
of
Pennsylvania
for
further
analyses
of
the
samples. After the analyses the blood samples will be destroyed.
X.
Information Security
BHProvide the precise plan how data is to be collected or acquired (repeat the same
information as listed under "Data Collection" section of this form.
(Section 2). Most of the
assessment measures will involve interviews (e.g. for the SCID form, or for the initial CBT-I
session). The only exceptions to this rule are for actigraphs and portable sleep monitors.
Actigraphs will be worn on the wrist for a few days at a stretch and the Veteran will be maintaining
a sleep diary for the sleep-wake schedule. The monitor has sensors attached to the body
recording oxygen saturation, airflow (nasal pressure), thoracic movements, snoring, body position
and the heart rate. The apparatus measures nasal pressure, which is an accepted surrogate
marker of air flow (instead of using oro-nasal thermistors, used in the earlier portable monitors).
Please see Table
1 for specific details on the assessment measures and the time frames of their
assessments.
2.
Provide a listing of the exact research data that will be stored, including but not limited to
signed,
original informed consent and HIPAA authorization forms, case report forms,
etc.
Data including but not limited to signed, original informed consent and HIPAA authorization forms,
case report forms, genetic analysis in the future, and results of the urine drug screen.
2.1 Indicate how
project's
research
data
(original and
all
copies)
will
be stored
and provide corresponding security systems,
a) Original assessment measure
on
paper and
pencil -
in
the
locked
drawers
of the
locked
office
spaces
of the
MIRECC
(room
228
B).
Some
of
the
data
may
be
stored
in
the
Principal
Investigator's
locked
drawer
in
his
locked
office
(Room
#
218,
Bldg
3);
we
will
transition data
collection and storage to the VA Redcap from the paper forms;
b)
Original Actigraphic data - in the desktop in the locked drawers of the locked office
space of the study coordinator within the MIRECC (room 228 B) or in the Principal
Investigator's locked drawer in his locked office (Room # 218, Bldg
3);
c) Electronic
data
with
identifying
information
within
the
electronic
servers
of
the CMCVAMC
(MIRECC
server (\\vhaphifpcmirecc\Research
Studies\Chakravorty - CBT-I)
or the
K:
drive
of the
PIA\vhaphiclunas11s
(K:)).);
d)
Electronic coded
data
without
the
HIPAA identifiers for statistical analyses - password protected computer within the
University of Pennsylvania;
e)
Electronic data captured
in the VA Redcap:
a secure
web application and back-end database model, developed
at Vanderbilt University
with collaboration from a consortium of institutional partners. Approved study staff
will enter data directly into REDCap, which obviates the need for transferring written
data into electronic form; this significantly improves the quality of data. The VA has
licensed its own version of REDCap housed on VA servers located within a VA data
center inside the VA firewall and therefore afforded the same network protections as
all VA
sensitive clinical
data. REDCap was developed specifically around HIPAA
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Security guidelines and is recommended to Perm Medicine researchers by our Office
of
Human
Research.
Relevant
HIPAA-compliant
features
include
password-
protected access to the system, restriction of access to specific clinical trial data to
designated users, audit trails of access and data updates, and built-in de-identification
functions
that
can be
used when
exporting
data
for
analysis. REDCap
has
been
disseminated
for
use
locally
at
other
institutions
and
currently
supports
170
academic/non-profit consortium partners on six continents and 13,000 research end-
users rwww.proiect-redcap.org). Approved study staff can access REDCap through a
web-based interface and securely input data from any location at the time of data
collection minimizing the need for travelling with either electronic or paper versions
of sensitive information.
VA REDCap database administrators will have control over electronic access rights
to REDCap databases. Only VA IRB approved individuals will be granted access to
this database.
This database keeps time-stamped
information on people
accessing,
inputting, and altering data in the database.
3.
Provide exact location where research data (original and all copies) will be stored and
secured.
a
Original
assessment
measure
on
paper
and
pencil -
in
the
locked
drawers
of the
locked office spaces of the MIRECC (room 228 B); some of the data may be stored
in
the Principal Investigator's locked drawer in his locked office (Room # 218, Bldg 3);
b
Original Actigraphic data -
in the desktop
in the
locked drawers of the locked
office
space
of the
study coordinator within the MIRECC
(room 228
B)
or
in the
Principal
Investigator's locked drawer in his locked office (Room # 218, Bldg 3);
c.
Electronic
data
with
identifying
information
within
the
electronic
servers
of
the
CMCVAMC (MIRECC server drive A\vhaphifpcmirecc\Research Studies\Chakravorty -
CBT-I)
or the K: drive of the PI AWhaphiclunasi 1 s (K:));
d.
Electronic
coded
data
without
the
17
HIPAA
identifiers
for
statistical
analyses
-
password protected computer within the University of Pennsylvania;
e
The
blood
samples
for
the
genetic
analyses
will
be
stored
at
a
freezer
within
the
CMCVAMC. When
all
the samples have
been
collected
and samples
are
ready
for
analyses we will transfer the samples with the coded identifier (and without any of the
17
HIPAA
identifiers)
from
the
CMCVAMC
to
the
designated
laboratory
at
the
University of Pennsylvania after obtaining the required CMCVAMC -IRB authorization.
The samples will be destroyed at the University of Pennsylvania after the genetic tests
have been conducted;
f.
Redcap:
a
secure
web
application
and
back-end
database
model,
developed
at
Vanderbilt University with
collaboration from
a consortium of institutional
partners.
Approved study staff will enter data directly into REDCap, which obviates the need for
transferring written data into electronic form; this significantly improves the quality of
data. The VA has licensed its own version of REDCap housed on VA servers located
within a VA data center inside the VA firewall and therefore afforded the same network
protections as all VA sensitive clinical data. REDCap was developed specifically around
HIPAA Security guidelines and
is recommended to Penn Medicine researchers by our
Office
of Human
Research.
Relevant
HIPAA-compliant
features
include
password-
protected
access
to
the
system,
restriction of access
to
specific
clinical
trial
data
to
designated users, audit trails of access and data updates, and built-in de-identification
functions
that
can
be
used
when
exporting
data
for
analysis.
REDCap
has
been
disseminated
for
use
locally
at
other
institutions
and
currently
supports
170
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academic/non-profit
consortium
partners on
six
continents
and
13,000
research
end-
users fwww.proiect-redcap.org). Approved study
staff can access REDCap through a
web-based
interface
and
securely
input
data
from
any
location
at
the
time
of data
collection minimizing the need for travelling with either electronic or paper versions of
sensitive information.
VA REDCap database administrators will have control over electronic access rights to
REDCap databases. Only VA IRB approved individuals will be granted access to this
database. This database keeps time-stamped information on people accessing, inputting,
and altering data in the database.
4.
Explain how data is to be transported or transmitted from one location to another. The
coded data (without the HIPAA identifiers) will be transferred using encrypted discs which wilt be
hand-carried by Dr. Chakravorty to Dr. Morales's office at the University of Pennsylvania.
4.1.
Informed Consent discloses PHI transported or transmitted off-site.
DYES
KlNO QN/A
4.2.
HIPAA Authorization discloses entities to whom PHI will be transported or transmitted. □
YES
IEINO
DN/A
4.2.1.
List all entities or individuals outside CMCVAMC to whom data is to be
disclosed, and the justification for such disclosure and the authority.
Dr.
Knashawn Morales and her staff at the Center for Clinical Epidemiology and
Biostatistics of the University of Pennsylvania. She and her staff will conduct
the statistical analyses of the coded research data without the HIPAA
identifiers.
4.3.
If yes,
list the exact data that will be transmitted.
Coded data from all the assessment
instruments and measures.
4.4.
If yes, explain how data will be protected during transmission outside of CMCVAMC.
The
data will be hand carried in encrypted compact disc/s by the Principal
Investigator to her office within the University of Pennsylvania.
4.5.
Off-site, provide exact location coded data without the 17 HIPAA identifiers will be
transferred for statistical analyses to the Center for Clinical Epidemiology and
Biostatistics, at the University of Pennsylvania.
4.5.1.
Data Use/Transfer Agreement IE1YES
QNO
QN/A
4.5.2.
Off-Site Storage/Transfer of Research Data KlYES
QNO
Qn/A
4.5.3.
Memorandum of Understanding QYES
KlNO
DlM/A
5.
List who
is to have access to the data and how they are to access
it (anyone who has
access
to
the
data
is
responsible
for
its
security).
1.
Principal
Investigator
-
source
documents,
electronic
spreadsheets,
and
compact
discs
with
backed
up
data;
2.
Study
Coordinator
-
source
documents,
electronic
spreadsheets,
and
compact
discs
with
backed
up
data;
3.
Statistician
(Dr.
Morales) - electronic coded
data without the
17 HIPAA
identifiers;
4.
CMCVAMC -IRB - data as deemed necessary; e) VA CS R & D, the grant funding agency - data
as deemed necessary.
6.
Describe who is to have access and be responsible for the security of the information. The
staff members who
will
have
access
to the
information
will
include
the
following:
a)
Principal
Investigator, Dr. Chakravorty; b) The Study Coordinator, Mr. He; c) Statistician at the University of
Pennsylvania
Dr.
Morales
(she
will
have
access
to
the
coded
data
without
the
17
HIPAA
identifiers); d) CMCVAMC -IRB; e) DMC; f) VA CS R & D, the grant funding agency. The security
of the information will be responsibility of everybody involved with the study and having privileges
of access to the study-related data.
7.
Provide mechanisms used to account for the information. The study related
staff will follow
the
guideline
of
keeping
the
identifiable
health
information
in
locked
drawers
or on
the
online
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password protected electronic drives of the CMCVAMC. The source documents will be maintained
in
the
locked
office space
of the MIRECC
in
room # 228
or
in
the
locked
clinic
office
of
Dr.
Chakravorty (Room # 218, Bldg
3). We will migrate over to the VA version of Redcap for future
data entry and the data will be stored within the VA VIRECC servers as mentioned previously. The
coded data without the 17-HIPAA identifiers will be transferred in encrypted compact discs by the
investigator himself to the statistician's office at the University of Pennsylvania. The statistician will
store the coded data with the HIPAA identifiers in the password protected computer in her office.
Once
the
data
analysis
is
completed
the
coded
data
will
be
destroyed
from
the
statistician's
computer.
8.
Give security measures that must be in place to protect individually identifiable information
if collected or used.
Identifiable information will be stored in locked office spaces of the MIRECC
(room 228), and in the Principal Investigator's locked office space (exact location TBA). Electronic
data with identifiable information will be stored in the password protected online servers of the
CMCVAMC and VIRECC, and the on the password protected desktops of the Study Coordinator
and the Principal Investigator.
9
How and to whom a suspected or confirmed loss of VA information is to be reported.
9.1.
The Investigator will notify the Information Security Officer, Privacy Officer, IRB, Associate
Chief of Staff for Research and Research Compliance Officer within one hour of a
suspected or confirmed loss of VA information.
10
Identify any circumstances that may warrant special safeguards to protect the rights and
welfare of subjects who are likely to be vulnerable including, but not limited to, those
subjects who may be susceptible to coercion or undue influence, and describe appropriate
actions to provide such safeguards.
The subjects will be reminded of the voluntary nature of the study during the initial screening,
during the informed consent session, as well as tested in the informed consent quiz.
11.
Electronic PHI will be stored on the following:
^nwr-o
i-im^
11.1. CMCVAMC desktop computer with password protection and/or encryption. |2S)YES UNO
I
|n/a
12.1.1.
If yes, identify where the desktop is located. Study coordinator's desktop in
room 228 of the MIRECC and the Principal Investigator's desktop in a
locked office space (exact room location TBA).
11
2. CMCVAMC secure server.
IKlYES DNO
Ql\l/A
11.2.1.
If yes, identify the CMCVAMC server. The MIRECC server
(\\vhaphifpcmirecc\Research Studies\Chakravorty - CBT-I), the Principal
Investigator's folder in the K: drive/\\vhaphiclunas1fs(K:)).
11.2.2. External drive that is password protected and/or encrypted. DYES QNO
Esl
N/A
11.2.2.1.
If yes, identify the external drive.
11.3.Off-Site server DYES
(ElNO
f1N/A nf off-site, attach at least one of the following.)
113 1. Provide exact location and the name of the off-site server.
1) secure VA
VIRECC server that houses the data from the VA Redcap; 2) Coded data
without the HIPAA identifiers will be transferred for statistical analyses to the
Center for Clinical Epidemiology and Biostatistics, at the University of
Pennsylvania.
11.3.2. Data Use/Transfer Agreement KlYES QNO QN/A
11.3.3. Off-Site Storage/Transfer of Research Data KlYES QNO UN/A
11.3.4. Memorandum of Understanding QYES
K)NO
DN/A
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12.
Explain how data is to be transported or transmitted from one location to another. The VA
Redcap
data
will
be
entered
into
the VA
Redcap
using
desktops
with
CMCVAMC
onto
the
password protected account for the study. The actigraph will be returned by the subject in-person
to the study coordinator or mailed out to the study coordinator in prepaid mailing envelopes. They
will be hand carried in compact discs by the study coordinator from the CMCVAMC sleep center to
room 228 (MIRECC). The blood samples for the genetic analyses will be stored in a freezer within
the CMCVAMC. When
all the samples have been collected and samples are ready for analyses
we
will transfer the samples with the coded
identifier (and without any of the HIPAA
identifiers)
from the CMCVAMC to the designated laboratory at the University of Pennsylvania after obtaining
the required CMCVAMC -IRB
authorization. The samples
will
be destroyed
at the
University of
Pennsylvania after the genetic tests have been conducted.
13.
Informed Consent discloses PHI transported or transmitted off-site.
DYES
14.
HIPAA Authorization discloses entities to whom PHI will be transported or transmitted
15.
List all entities or individuals outside CMCVAMC to whom data is to be disclosed, and the
justification for such disclosure and the authority. The data will be disclosed to the following
entities or individuals: a) CMCVAMC -IRB as required for regulatory purposes; b) VA CSR & D,
the grant funding agency as deemed necessary; c) Dr. Knashawn Morales - the designated
statistician associated with the study at the Center for Clinical Epidemiology and Biostatistics of
the University of Pennsylvania. Dr. Morales will receive the coded data without the 17 HIPAA
identifiers, which will be hand carried by the principal investigator on a compact disc to her office
within the University of Pennsylvania.
16.
Clarify what protection
exists for a database.
The tracking database with the demographic
identifiers
will
reside
within
the
password
protected
electronic
servers
of
the
CMCVAMC.
In
addition,
the polysomnographic data
with the
identifiers
will be
stored
in the case
report forms
within the
locked MIRECC space
of CMCVAMC. The
electronic databases with the coded data
relating to the study will exist in password protected electronic servers of the CMCVAMC and the
VA Redcap-related VIRECC servers.
The coded electronic polysomnographic data will be stored
within the password protected electronic servers of the CMCVAMC. The actigraphic data
will be
stored
in
the
hard
drive
of the
password-protected
desktops
of the
study
coordinator and
the
principal investigator. The electronic actigraphic data will be stored in compact discs in the locked
desk drawers of the desks of the study coordinator and the principal investigator. The coded data
for statistical analyses at Dr. Morales's office will be stored in the password-protected computer in
the University of Pennsylvania.
16.1. Data is stored:
16.1.1. With identifiers-IEIYES
16.1.2. Coded-EYES
DNO
16.1.3. De-Identified- DYES
EO
16.1.4. Provide the exact list of identifiers that will be stored. The database will
be stored in the password protected online drives of the CMCVAMC. The
tracking database will have the study identification number, subjects full name,
age, race, date of birth, the last 4 of his/her social security number, the contact
telephone numbers, date of telephone screening and date of informed consent
process, reason for ineligibility (if applicable). The other forms including the
actigraphic data will be coded (with the unique 4-digit identification number)
and without the HIPAA identifiers. They will however have dates of the
conduct of study procedures.
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18.
on
paper
will
be
stored in locked cabinets and locked desk drawers in the MiRtuu omce space in room nu>..uc.
*.«,
B
Electronic data will either be stored on the password protected online drive of the CMCVAMC.
The actigraphic data
will be stored on the research
assistant's password
protected desktop,
the
principal
investigators
desktop,
and
backed
up
on
a
compact
disc
as
recommended
by
the
manufacturer and as is being done in our current CBT-I pilot study. All the discs will be stored in the
principal investigators locked office space with restricted access (room # TBA), in a locked cabinet.
CMCVAMC Information Security Officer and Privacy Officer will be notified within one hour of the
improper use or disclosure, as well as the IRB, Associate Chief of Staff for Research (ACOS/R) and
Research Compliance Officer.
17
1 The Investigator must notify the Information Security Officer, Privacy Officer, 1Kb,
Associate Chief of Staff for Research and Research Compliance Officer within one hour
of the improper use or disclosure.
ic thprp a plan to apply for a Certificate of Confidentiality? DYES
[E|NO
QN/A
18.1. If yes, provide a copy of the certificate with this application or to the IRB Office as soon as
received.
19.
Record Retention:
19 I.The required records, including the investigator's research records, must be retained until
disposition instructions are approved by the National Archives and Records
Administration and are published in VHA's Records Control Schedule (RCS 10-1).
VHA
Handbook 1200.05 §26.h
19 2 Until a schedule for local research records is published, ALL records including identifiers
must be retained." ORO/ORD Guidance on Informed Consent Form Modifications
Addressing VA Record Retention Requirements (July 23, 2009)
19.3. If there are additional procedures for record retention, explain further.
N/A
Y
Qualification of the Investigators
1.
Provide
a
description
of the
qualifications
of each
investiaator/co-investigator and
their specific
role in the study.
(i)
(ii)
(iii)
Dr
Subhajit
Chakravorty
-
is
the
principle
investigator
for
this
study.
He
is
a
start
physician
here
at
the
Philadelphia
Veterans
Affairs
Medical
Center,
a
researcher
associated with the MIRECC, and a faculty member of the Penn Sleep Center. He
is
certified
in
Psychiatry
and
with
sub-specialty
certifications
in
Sleep
Medicine
and
Addiction Medicine. He will be a backup provider for the CBT-I; in addition, he will be a
backup staff for all the duties associated with the study from answering questions from
prospective participants to scheduling appointments for veterans in clinic at the end of
Sean* He/alternative Study Coordinator - will coordinate the study. S/he will conduct the
following
obligations associated with the study;
a) Answering telephone
calls for
potential
participants;
b) Screening
participants for inclusion-exclusion
criteria;
c)
Coordination
of
study
visit
procedures;
d)
drawing
and
processing
the
blood
samples; e) Uploading data onto online servers; f) Communication with the IRB; g)
Any other required study-related documentation.
Certified Behavioral Sleep Medicine Specialist
(Dr. James Findley) - s/he will conduct the
cognitive
behavioral
therapy
for
insomnia
and
the
Quasi-Desensitization
Therapy
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(QDT) along for the participants in the study;
Dr. Chakravorty will function as the back
up behavioral sleep medicine specialist for this study
2
If applicable, the Principal Investigator must identify a qualified clinician to be responsible
for all study related healthcare decisions. Dr. Chakravorty will be the clinician involved in
making the study related healthcare decisions for the subjects. The designated Behavioral Sleep
Medicine specialist will function as a backup to Dr. Chakravorty in making health care decisions
for the Veterans in the study.
3.
PI should submit a current, dated CV with each new initial review.
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