The Efficacy of Masked Tapering on Discontinuation of Hypnotics in Older Veterans
Phase: NA
Conditions: Insomnia
Sponsor: VA Office of Research and Development

Study Protocol   
 
1 
   V 6.16.2023 
 
 
 
STUDY PROTOCOL 
 
The efficacy of masked tapering on discontinuation of hypnotics  
in older Veterans 
(SWITCH study) 
 
PI: Constance H. Fung, MD, MSHS 
 
Funded by VA Health Services Research & Development Service 
 
NCT03511209 
 
Document date: 6.16.2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study Protocol   
 
2 
   V 6.16.2023 
SPECIFIC AIMS 
 
Hypnotics such as benzodiazepines and benzodiazepine receptor agonists (BzRAs or Z-drugs) are often 
prescribed for insomnia.3 Among Veterans attending outpatient clinic appointments, approximately one-quarter 
use hypnotics (or bedtime alcohol).4 Hypnotics use is associated with an increased risk of falls5;6 and worse 
cognition7 in older adults. Discontinuing hypnotics often attenuates or reverses these negative effects,8;9 and 
the Department of Veterans Affairs (VA) has initiatives to reduce hypnotic use among older Veterans. Current 
discontinuation strategies focus on tapering off the hypnotic and/or treating insomnia symptoms. Common 
strategies include supervised gradual taper (SGT), cognitive behavioral therapy targeting hypnotic withdrawal 
(CBT-HW), cognitive behavioral therapy for insomnia (CBTI), and combination therapy (SGT+CBTI). Yet up to 
40% of patients eventually resume use of hypnotics with these strategies, suggesting that other mechanisms 
need to be targeted to achieve and sustain high rates of non-use.10;11 
 
Another mechanism that may be a viable target for achieving hypnotic discontinuation and sustaining long-term 
non-use is the placebo effect,12-14  which is characterized by real improvements in sleep arising from 
psychosocial aspects of treatment rather than drug effects alone. We recently developed and tested the 
feasibility of an intervention that targets the placebo effect. Our intervention retains core components tested in 
prior studies for achieving hypnotic discontinuation (i.e., SGT+CBTI), but adds a novel feature—“masked” 
tapering. Masking is achieved by encapsulating hypnotics (prepared by a compounding pharmacy) so the 
patient, who has consented to a gradual taper, is unaware of the actual dose in each capsule until the end of 
the taper, when the tapering schedule is revealed to the patient. Towards the end of the taper, placebo 
capsules are used. Through novel cognitive exercises, the therapist uses masking as a tool to challenge 
expectancies about hypnotics, which may be contributing to chronic use, and to augment CBT-HW (e.g., 
preparing for withdrawal). Coupled with CBTI (i.e., stimulus control, sleep restriction, cognitive therapy for 
insomnia, and relaxation), the intervention targets the placebo effect and the factors contributing to insomnia 
symptoms and helps patients safely taper off their hypnotic and develop relapse prevention skills.  
 
The objective of the proposed study is to test whether hypnotic discontinuation rates can be increased with a 
novel set of cognitive exercises that use supervised masked tapering as a core tool to challenge expectancies 
about hypnotics. In a 4-year randomized trial (N=132 participants), we will measure the effects of a 2-month 
program entitled, Masked Taper plus cognitive behavioral therapy-augmented program (MTcap), which 
combines novel cognitive behavioral therapy exercises, supervised masked hypnotic tapering, CBT-HW, and 
CBTI. We will compare outcomes in MTcap to a supervised unmasked (traditional) SGT+CBTI program post-
treatment and at 6 months follow-up to determine whether the addition of the novel cognitive exercises and 
masked tapering reduces expectancies for hypnotics, improves hypnotic discontinuation rates, and improves 
insomnia symptoms. The rationale is that hypnotic-related placebo effects can be specifically targeted with our 
novel intervention. The following are the primary aims for the proposed project: 
 
Aim 1: Determine whether MTcap improves hypnotic discontinuation more than SGT+CBTI post-treatment and 
at 6 months follow-up. 
• H1a: Participants who receive MTcap will have increased likelihood of hypnotic discontinuation post-
treatment and at 6 months follow-up compared with those who receive SGT+CBTI. 
• H1b:  Participants who receive MTcap will use less hypnotic medication post-treatment and at 6 months 
follow-up compared with those who receive SGT+CBTI. 
Aim 2: Determine whether MTcap improves insomnia severity more than SGT+CBTI at 6 months follow-up. 
• H2: Participants who receive MTcap will have lower Insomnia Severity Index scores at 6 months follow-up 
compared to SGT+CBTI. 
Aim 3: Determine whether MTcap improves expectancies about hypnotics more than SGT+CBTI post-
treatment and at 6 months follow-up.  
• H3: Dysfunctional Beliefs and Attitudes About Sleep (DBAS) – Medication Scale ratings will improve 
compared to SGT+CBTI post-treatment and at 6 months follow-up. 
 
A secondary aim is to compare balance and cognition in the MTcap arm compared with the SGT+CBTI arm at 
follow-up. We hypothesize that participants who receive MTcap will have better balance and cognition 
compared to those who receive SGT+CBTI post-treatment and at 6 months follow-up. 
 

Study Protocol   
 
3 
   V 6.16.2023 
This proposed study will test the effects of an innovative intervention on chronic hypnotic use among older 
Veterans, which is a prevalent, high-priority, and challenging problem. The intervention was designed based on 
extensive feasibility testing. If successful, this novel intervention could lead be disseminated throughout the VA 
and lead to significant improvement in ongoing efforts to decrease chronic hypnotic use among older Veterans.   
 
RESEARCH DESIGN AND METHODS 
 
Basic Study Design (Figure 1): The proposed study is a 4-year 
randomized trial to test the efficacy of a novel treatment program for 
achieving hypnotic discontinuation among older Veterans receiving 
outpatient prescriptions for hypnotics.  
Setting: The proposed study will be performed within the VAGLA, 
where approximately 1,650 older Veterans receive each quarter the 
benzodiazepines and Z-drugs targeted in this study. All in-person study 
assessments and treatment sessions will be completed within VAGLA.  
Specific VAGLA facilities include: West Los Angeles Medical Center, 
Sepulveda Ambulatory Care Center, Los Angeles Ambulatory Care 
Center and VA Community-based Outpatient Clinics in Lancaster, 
Oxnard, and Bakersfield. Our research staff may meet participants to 
drop/off or pick up study materials, and if necessary, to conduct 
baseline and follow-up assessments. Recruitment sample: 
The sampling frame for this study will consist of Veterans ≥ 55 who 
received hypnotic prescriptions for three or more months from VAGLA 
pharmacies within the past year. To obtain this sample we will access 
VA administrative data sources, seek patient referrals from VAGLA 
healthcare providers, and distribute recruitment flyers in VA GLAHS 
outpatient clinics. Each of these recruitment strategies is described 
below: 
1. VA Corporate Data Warehouse (CDW)  
Authorized VA project team member(s) will work with VINCI 
programmers to pull a sample using the VA Corporate Data Warehouse 
(CDW). Study inclusionary criteria will be applied to select eligible Veterans for recruitment. To help capture 
eligible patients with fresh contact information, this process will be repeated at least 2-3 time during the study 
recruitment period.   
The variables in the sample file will include the following: 
 • Unique patient identifiers (e.g. Scrambled SSN, Patient ICN, PatientSID, etc.) 
 •  Contact information (e.g. Name, residential address, zip code, telephone numbers)  
•  Demographic and Veteran Characteristics information (e.g. date of birth, gender, race/ethnicity, date of 
death, Veteran status) 
•  Hypnotic medications (e.g. outpatient medication names, dose, prescription number, issue date, etc.) 
A link file will be created using the sample file to associate the project specific study ID with the Veterans’ 
unique identifier (PatientICN/PatientSID, or SSN/scrambled SSN) which can be used to access VA 
VINCI/CDW data. The new records pulled with each additional sample pull will be added to our link file to 
create a single cumulative file of all sampled Veterans.  All records will be assigned a study ID number that will 
serve as the primary key for matching data from the additional sources.  The Link File will be stored on a 
restricted-access folder on the CSHIIP-managed secure server behind the VA firewall and is never transferred 
during the project, nor will it be accessible to anyone other than authorized VA project team member(s). 
 
We will use the same process to identify from CDW Veterans who receive care at the Tibor Rubin VA Medical 
Center in Long Beach (VALB).  Many VALB patients live close to the VAGLA campus in West Los Angeles and 
may be willing to participate in the study.  If these VALB Veterans enroll in the study, all study activities will be 
conducted at VAGLA. No study activities will be done at VALB. 
 
Figure 1 

Study Protocol   
 
4 
   V 6.16.2023 
We will also use the same process to identify from CDW Veterans who receive care at the VA Loma Linda 
Healthcare System. If these Loma Linda Veterans enroll in the study, study activities will be conducted via 
telehealth at VAGLA.  
 
2. VA Academic Detailing Service Benzodiazepine/ZDrugs Dashboard 
The VA Academic Detailing Service has compiled and maintains a database of VA GLAHS patients who are 
prescribed benzodiapezines and benzodiapezine receptor agonists (Z-drugs).  This database, or dashboard, 
can be found on their Data Resources website. In this dashboard, the names and mailing addresses of VA 
GLAHS patients prescribed benzodiazepines and Z-drugs are listed along with prescribing information. We will 
access this dashboard to confirm the CDW sample.    
The variables that will be abstracted from the dashboard will include: 
      - Unique patient identifiers (PatientSID, last 4 SSN) 
      - Contact information (name, residential address, zip code) 
      - Patient characteristics (age) 
      - Hypnotic medications (medication names, number of prescriptions,  
        prescriber, dispensing location, prescribed for insomnia or PTSD, next primary care  
        and mental health appointment dates and locations)  
 
3. Consults to VAGLA Insomnia clinics 
Research staff will access the VA electronic consults made to Insomnia clinic. Patients who are referred to the 
clinic for cognitive behavioral therapy for insomnia treatment will be identified. Study staff will then review 
demographic information, medications and clinic notes to determine basic eligibility criteria (e.g., age ≥ 55, 
prescribed a hypnotic medication) of these Veterans. Names, addresses and telephone numbers of Veterans 
who meet these basic eligibility criteria will be abstracted from the medical record by research staff and entered 
into a study database.  
 
4. Referrals from VA GLAHS healthcare providers  
A recruitment flyer with a cover memo to VA GLAHS providers with be distributed to providers in primary care, 
mental health, and sleep medicine clinics (see attached Provider Memo and Recruitment Flyer). The memo 
describes the study and basic eligibility criteria and invites providers to distribute the flyer to patients who might 
be appropriate for the study. Providers are also invited to send an encrypted email to the study team with the 
name and last four social security numbers of patients who may be eligible for the study.  When the research 
team receives the name of a patient from a provider, research staff will review the CPRS electronic medical 
record to determine if the patient meets the basic study eligibility criteria (e.g., age, prescribed one of the 
targeted hypnotics to treat insomnia) (see CPRS data abstraction form). Patients who meet these criteria will 
receive a recruitment telephone call from research staff as described below (see telephone eligibility 
screening). 
 
5. Self-referral from Veterans 
We will also post the recruitment flyer (which may also be enlarged to the size of a poster board) in outpatient 
clinic waiting areas (our research team will seek approval from appropriate VA GLAHS authorities prior to 
displaying any flyers/posters) and at community sites frequented by Veterans (e.g., Veteran Centers, DAV 
halls, Elk Lodges, senior centers). Written permission to post the recruitment flyer at community sites, and for 
study staff to provide verbal information about the study, will be obtained from each site (see attached Off-site 
Permission form) before flyers are posted. 
 
6.   e-Recruitment: We will put information about the study on VA Greater Los Angeles Facebook, VA 
Greater Los Angeles Twitter, and the new VA Greater Los Angeles Research and Development website (see 
attached social media announcements). Patients who are interested in the study will be advised to call the 
study office to learn more about the study.  
 
If a Veteran calls the study office in response to seeing a flyer, poster, social media announcement, or 
receiving a flyer from a provider, research staff will follow the protocol described below (see telephone eligibility 
screening).  
Table 1. Inclusion and Exclusion Criteria 
Inclusion criteria: 

Study Protocol   
 
5 
   V 6.16.2023 
Inclusion and Exclusion Criteria 
Table 1 lists the inclusion criteria for the sampling frame 
and enrollment into the study.  We anticipate enrolling 
up to 600 participants and randomizing 132 to receive 
the intervention.  Exclusion criteria for enrollment and 
randomization are also listed in Table 1.  
 
Recruitment, enrollment  
• 
Recruitment letter 
Veterans identified from the CDW database will be 
mailed a recruitment letter and opt-out card (see 
Recruitment letter and Opt-out card). Veterans will be 
asked to return the opt-out card in a postage-paid 
envelope within 7 days of the letter mail date to indicate 
whether they wish to be called by our research staff. 
The letter will explain that research staff will call the 
Veteran if the opt-out card is not returned within the 7-
day timeframe. In total, we plan to send this recruitment 
package to approximately 2500 older Veterans over the 
first three years of the study.  
We will obtain a revised list from both databases 
throughout the first 3 years of the study as new names 
are needed for recruitment.  This process will enable us 
to have a current list of names for our sample. In our 
previous work, we found that Veterans with a visit in the 
prior 2 quarters were more likely to have a valid mailing 
address and to participate in research than Veterans 
who had not received care in that timeframe.  
 
• 
Telephone eligibility screening  
Study staff will telephone potential participants who 
were sent the recruitment letter but did not return the “opt out” card. They will also telephone Veterans who 
were referred to the study by a VA provider.  Staff will leave up to 4 telephone messages. Veterans who do not 
return our call after the 4 messages will be considered as “not interested” in participating.   
During this telephone call, the study will be explained and verbal consent for screening will be obtained from 
Veterans who express interest in the study (see Telephone Screening Script). Additional eligibility criteria will 
be assessed with a structured screening questionnaire (see Telephone Screening Questionnaire). The 
screening questionnaire will include items to assess the following: 1) current insomnia symptoms, 2) hypnotic 
use, 3) number of months and nights per week hypnotic is used, 3) major health events (e.g., surgery) within 
the past month (individuals with a recent major event will be re-contacted 3 months later), 4) housing situation 
(e.g. homelessness), 5) access to transportation to the medical center, 6) perceived physical, emotional or 
substance use being a barrier to participating in the study sessions. The same script and telephone screening 
questionnaire will be used for Veterans who call the study office in response to the recruitment flyer.   
Following completion of the telephone screening questionnaire, eligible and interested Veterans will be 
scheduled for an initial meeting (in-person or by video) to obtain written informed consent. Potential 
participants also will be informed that they can receive a blank written informed consent form in the mail to 
provide them with sufficient time to consider participation and discuss participation with family members, 
should they so desire. 
During the telephone screening, potential participants will also be informed that prior to the consent visit, 
research staff will review their CPRS medical record to identify hard exclusion criteria, such as clear diagnosis 
of bipolar disorder, substance abuse, benzodiazepine/z-drug doses that are supratherapeutic, or untreated 
severe obstructive sleep apnea. Participants who have any of these exclusionary criteria will be informed that 
they currently do not meet study inclusion/exclusion criteria and the in-person or VVC consent appointment will 
be cancelled. 
 
• 
In-person consent visit 
 • Age > 55 years 
  • Use of lorazepam, alprazolam, temazepam, clonazepam, and/or zolpidem for 
current or prior insomnia symptoms 2 or more nights per week57;58 for at least 
3 months 
 • Current or prior insomnia symptoms 
 • Available to attend weekly in-person or video sessions over 9 weeks 
Exclusion criteria: 
High risk for complications in outpatient hypnotic discontinuation program: 
 • Seizure disorder 
 • Supratherapeutic/high baseline hypnotic dose (> diazepam-equivalent of 8 
mg/night). Note that for individuals on > 1 of the targeted hypnotics, total 
baseline dose in diazepam-equivalents will be calculated & if > 8 mg/night, 
individual will be excluded.  
 • High risk of complicated withdrawal; benzodiazepine intoxication or current or 
past symptoms of complicated benzodiazepine/alcohol withdrawal (e.g., 
seizure, delirium at baseline) 
 • Polydrug use (e.g., chronic high dose opioids) 
 • Unable to keep study medications in secure location 
 • Evidence of prescription fraud (e.g., multiple prescriptions for same drug 
filled at VA and non-VA pharmacies, diversion) 
Discontinuation of hypnotic not appropriate:  
 • Study-targeted hypnotic used to treat another clinical condition (e.g., REM 
sleep behavior disorder) 
 • Not willing to begin hypnotic discontinuation program 
Poor candidate for CBTI:  
 • Presence of bipolar disorder 
 • Cognitive impairment (e.g., Mini-Mental State Examination < 24) 
 • Sleep/wake difficulty is better explained by another sleep disorder such as 
restless legs syndrome, narcolepsy, insufficient sleep syndrome, or circadian 
rhythm sleep-wake disorders 
 • Untreated sleep-disordered breathing (apnea-hypopnea index ≥ 30) 
Moderate sleep apnea (apnea-hypopnea index between 15-29.99) and 
daytime sleepiness (Epworth Sleepiness Scale score >10) 
 • Medically/psychiatrically unstable (e.g., recent major hospitalization or 
planned major surgery during the study; psychosis, suicidal, active 
alcohol/substance abuse based on history and medical records) 
 • Unstable housing situation  

Study Protocol   
 
6 
   V 6.16.2023 
When a potential participant comes to the consent visit, a trained research staff member will discuss the study 
with her/him and answer any questions. Potential participants will be shown the wrist actigraph and FDA-
approved, commercially available home sleep apnea testing device (e.g.,WatchPat monitoring equipment) to 
ensure that they become familiar and comfortable with this equipment. In our ongoing studies, nearly all 
individuals elect to sign the informed consent form at the time of the in-person meeting. However, Veterans will 
have the option of taking a blank consent form home to discuss with their family/friends. Capacity to give 
informed consent will be evaluated with a brief questionnaire (see Evaluation to Sign a Consent Form for 
Research), previously approved by the IRB, that asks the Veteran to recount major procedures and risks of the 
study. Veterans who are unable to provide informed consent will be excluded; proxy consent will not be 
pursued. Participants who are able to provide informed consent will be asked to sign the written informed 
consent form and HIPAA authorization and will be provided with copies. 
 
Amendment to recruitment protocol 
We will also recruit UCLA patients. The recruitment methods will differ from those above because they involve 
patients from a different institution with their own IRB and Compliance Office (Privacy). The recruitment will 
begin with a query of the UCLA Data Warehouse to identify patients on target medications. Second, potentially 
eligible patients will be sent a UCLA recruitment letter and opt-in/out form. Patients who do not opt-out will be 
contacted following a UCLA IRB approved telephone screening protocol.  UCLA patients who are eligible and 
interested in enrolling in the study will be invited to a consent appointment at the VA. At this point forward, all 
study activities will align with the approved protocols for the current VA study. These UCLA patients will be 
enrolled as non-Veterans. The informed consent process will be identical to the process described above, 
except on-Veteran participants will sign a separate consent form that includes a statement that an electronic 
VA medical record will be established for all non-Veteran participants.  They will also sign the VA HIPAA, and 
VHA Form 10-0483, Acknowledgement of the Notice of Privacy Practices.  Non-Veteran participants also will 
be asked to sign a UCLA HIPAA form, so Dr. Fung and other study staff who have a UCLA appointment, can 
access the UCLA electronic medical record.  
 
Amendment for telehealth option 
The process for obtaining consent by VA Video Connect (VVC) is described below:  
1. 
Research staff will schedule a VVC visit 
2. 
A Virtual Care Manager Ad Hoc Video Visit invitation is auto-generated by VVC and is sent via the 
Virtual Care Manager interface to the participant 
3. 
Research staff will send participants an email to confirm the appointment and notify them that a VVC 
email should arrive in their inbox with a link to use to connect to VVC 
4. 
Study materials mailed to participants will include: 
• 
Cover sheet describing content of package 
• 
Informed consent, VA HIPAA form, and if applicable for non-Veterans, a UCLA HIPAA form 
• 
Addressed, postage-paid envelope to return consent/HIPAA forms 
• 
Paper disposable ruler (needed for assessment visit to obtain neck circumference) 
 
VVC Consent Visit  
A member of the study team will follow the in-person protocol for obtaining consent, including showing potential  
participants the wrist actigraph and portable sleep apnea screening device, administering the capacity to give 
informed consent questionnaire, answering all questions, and observing the participant sign the informed 
consent and HIPAA forms.  Participants will be instructed to mail the signed forms back to a study post office 
box using the postage-paid return envelope.  At the end of the visit, an appointment will be scheduled for the 
first baseline assessment visit. 
 
Amendment for telephone visit 
If video connection is not possible due to technical issues (e.g., bandwidth connectivity issues, software 
problems, hardware issues), research staff will conduct the consent visit via telephone.  The participant will 
already have received the necessary study materials (i.e., informed consent, HIPAA form, return envelope, 
paper disposable ruler). Staff will follow the same protocol for obtaining consent as is described above for the 
VVC visit, with the exception that they will not be able to observe the participant sign the forms. 
 
 

Study Protocol   
 
7 
   V 6.16.2023 
Baseline Assessment 
After participants have provided written informed consent (in-person Visit 1), they will complete a baseline 
assessment that consists of 2 visits (each 45-60 minutes) to the study site. Participants who complete the 
baseline assessment will receive $25 for their travel and time. Components of the baseline assessment will 
include: 
• Research assistant administered questionnaires (see Table 2) 
• Blood pressure, pulse and respiration  
• A wrist actigraph will be given to participants to wear at home for 1 week  
• A sleep diary will be given to participants to complete while wearing the actigraph  
• Screening for sleep apnea – all participants will be administered the STOP-Bang questionnaire to screen for 
symptoms of sleep apnea. If a participant scores > 4 on the STOP-Bang and does not have documentation 
of a previous sleep study in the CPRS medical record, s/he will be sent home with a portable sleep apnea 
screening device (WatchPAT) to wear for one night. The participant will return the home sleep apnea testing 
device (e.g., WatchPAT) the next day to the research office. 
• Hypnotic medication log - Using a structured hypnotic abstraction form (see Hypnotic Abstraction Form), we 
will review CPRS to obtain data about VA hypnotic prescriptions. We will also query the California 
Controlled Substance Utilization Review and Evaluation System (CURES) database to obtain data about 
prescriptions of controlled substances. 
 
Amendment for telehealth option 
During the current pandemic, we have added the option to replace in-person research contacts with remote 
contacts using the VA Video Connect (VVC) platform. This is the same platform that VA clinicians use for video 
health visits. Use of the video option will be based on current VA guidelines for in-person visits and participant 
preferences. 
The process for completing the baseline assessment by VVC is described below:  
1. Research staff will schedule a VVC visit 
2. A Virtual Care Manager Ad Hoc Video Visit invitation is auto-generated by VVC and is sent via the Virtual 
Care Manager interface to the participant 
3. Research staff will send participants an email to confirm the appointment and notify them that a VVC email 
should arrive in their inbox with a link to use to connect to VVC 
4. Participants will be provided instructions for preparing for the baseline assessment (e.g., anticipated 
duration, equipment/materials needed, staff contact information)   
 
Amendment for telephone option 
If video connection is not possible due to technical issues (e.g., bandwidth connectivity issues, software 
problems, hardware issues), research staff will conduct the baseline visit via telephone.   
 
VVC/Telephone Baseline Visit Procedures 
Staff will conduct the 2 baseline assessment visits by VVC/telephone following the same protocol as used 
during in-person visits, except that the 1-leg balance test will not be performed. Certain items needed for the 
baseline assessment will be mailed to participants prior to the second baseline visit. These items include: 
• 
Wrist actigraph  
• 
7-day sleep diary 
• 
Hypnotic medication log 
• 
Paper copies of the Trails, Digit Symbol/Symbol Copy tests  
• 
Sleep apnea screening device (e.g., Watch PAT), if STOP-BANG score > 4 
• 
Postage-paid, pre-addressed, insured delivery box (“Return Delivery” Box) 
 
Participants will also have the option to meet staff at a VA GLAHS facility that is near their home to pick-up and 
return study devices//materials.  In those circumstances, staff will meet the participant in a parking lot or lobby 
to exchange devices, while maintaining social distancing.  
If it is determined that the MINI needs to be administered to a participant, a separate VVC visit will be 
scheduled. 

Study Protocol   
 
8 
   V 6.16.2023 
 Table 2:  Data Collection Instruments 
Time point for 
data collection 
    Instrument NAME 
Standard or 
Study-Specific 
Purpose 
Baseline 
Intervention 
Post 
6-months 
Self-Administered Comorbidity 
Questionnaire15 
 Standard     
Self-reported 
medical/psychological 
conditions 
X 
 
 
 
Insomnia Severity Index (ISI)16 
 Standard     
Insomnia symptoms severity 
X 
X 
X 
X 
Pittsburgh Sleep Quality Index 
(PSQI)17 
 Standard     
Self-reported sleep quality 
X 
X 
X 
X 
Dysfunctional Beliefs and Attitudes 
about Sleep – 16 item (DBAS-16)18 
 Standard     
Beliefs about insomnia 
X 
 
X 
X 
Morningness Eveningness 
Questionnaire (MEQ)19 
 Standard     
Circadian rhythm sleep 
disorders 
X 
 
 
X 
Disturbing Dream/Nightmare 
Severity Index (DDNSI)20 
 Standard     
Frequency and severity of 
nightmares 
X 
 
X 
X 
Restless Leg Syndrome  
questionnaire (RLS)21 
 Standard     
Symptoms of restless legs 
syndrome 
X 
 
X 
X 
STOP-Bang questionnaire22 
 Standard     
Symptoms of sleep apnea 
X 
 
 
 
Epworth Sleepiness Scale (ESS)23 
 Standard     
Daytime sleepiness 
X 
X 
X 
X 
Brief Pain Inventory (BPI)24 
 Standard     
Pain assessment 
X 
 
X 
X 
WHO Quality of Life -BREF 
(WHOQOL-BREF)25 
 Standard     
Health-related quality of life 
X 
 
X 
X 
Mini-International Neuropsychiatric 
Interview (MINI) 26 
 Standard     
Full interview or partial interview 
using only the depression, 
mania, psychosis, and 
suicidality symptom modules.  
Only used with participants who 
have history of bipolar disorder. 
X 
 
 
X 
Primary Care Post-Traumatic 
Stress Disorder (PC-PTSD) 27 
 Standard     
PTSD symptoms, exposure 
X 
 
X 
X 
Generalized Anxiety Disorder 
(GAD-7)28 
 Standard     
Anxiety symptoms 
X 
 
X 
X 
Patient Health Questionnaire-
Depression Module (PHQ-9)29 
 Standard     
Depression symptom severity 
X 
 
X 
X 
Alcohol, Smoking and Substance 
Involvement Screening Test 
(ASSIST)30 
 Standard     
Screens for substance abuse 
X 
 
 
 
Trails A & B tests31 
 Standard     
Mental processing speed, 
attention, executive functioning 
X 
 
X 
X 
Digit Symbol Substitution and 
Symbol Copy32 
 Standard     
Mental processing speed and 
attention 
X 
 
X 
X 
Mini-Mental State Examination 
(MMSE)33 
 Standard     
Cognitive status 
X 
 
X 
X 
One-leg standing balance34 
 Standard     
Balance measurement 
X 
 
X 
X 
Benzodiazepine Dependence 
Questionnaire (DBEP)35 
 Standard     
Symptoms of benzodiazepine 
dependence 
X 
 
X 
X 
Clinical Institute Withdrawal 
Assessment Scale – 
Benzodiazepines (CIWA-B)36 
 Standard     
Symptoms of benzodiazepine 
withdrawal 
X 
X 
X 
X 
Credibility/expectancy 
questionnaire (CEQ)37 
 Standard     
Self-reported confidence in 
treatment  
X 
X 
X 
X 
Demographic questions 
Study-specific 
(attached) 
Characteristics of participants 
(e.g., marital status, living 
location, employment) 
X 
 
 
 

Study Protocol   
 
9 
   V 6.16.2023 
Fall event question 
Study-specific 
(attached) 
History of slips/trips/falls  
X 
 
X 
X 
ICSD-3 questions 
Study-specific 
(attached) 
Symptoms of insomnia based 
on ICSD-3 criteria 
X 
 
X 
X 
Additional comorbidity questions 
Study-specific 
(attached) 
Self-reported 
medical/psychological 
conditions 
X 
 
 
 
Nighttime urinary symptoms 
questions 
Study-specific 
(attached) 
Frequency and impact of 
nighttime urination 
X 
 
X 
X 
Hypnotic abstraction form 
Study-specific 
(attached) 
Prior and current use of 
hypnotics 
X 
 
X 
X 
Medication log 
Study-specific 
(attached) 
Medications taken during week 
while wearing wrist actigraph 
X 
 
X 
X 
Sleep diary 
Study-specific 
(attached) 
Self-reported daily sleep 
patterns  
X 
X 
X 
X 
Fall log 
Study-specific 
(attached) 
Self-reported daily fall record   
 
 
X 
X 
Treatment arm question 
Study-specific 
(attached) 
Self-reported question asking 
participant which treatment 
received 
 
 
 
X 
Watch-PAT instruction sheet 
Study-specific 
(attached) 
Questions about sleep apnea 
device use and times 
associated with Watch-PAT use 
X 
 
 
 
Subject Contact Information sheet 
Study-specific 
(attached) 
Updated contact information 
 
 
X 
 
  
Eligibility determination for randomization 
The final determination of eligibility will take place during a weekly meeting of the investigators. At least one 
physician (Fung or Alessi) and at least one sleep psychologist (Martin) will participate at these meetings. 
During this “pre-randomization review” meeting, individuals who no longer meet the hypnotic criteria at the 
baseline assessment will be excluded. Individuals adherent to sleep-disordered breathing therapy and restless 
legs syndrome (RLS) therapy or with insomnia symptoms incompletely explained by RLS will be considered for 
intervention, as would be done in clinical practice. Individuals with insomnia symptoms due to circadian rhythm 
sleep disorders or inadequate opportunity for sleep will be excluded.  
 
Participants with an apnea-hypopnea index ≥ 30 (from home sleep apne testing device such as WatchPAT) will 
not be eligible for randomization. Participants with an apnea-hypopnea index between 15 and 29.99 (moderate 
sleep apnea) and with daytime sleepiness (Epworth Sleepiness Scale score > 10) will also not be eligible for 
randomization. Participants with an apnea-hypopnea index between 15 and 29.99 and no daytime sleepiness 
will be eligible for randomization. We will inform participants with an apnea-hypopnea index > 15 that they may 
have sleep apnea and, with their permission, will initiate a consult to the VA GLAHS Sleep Center, or inform 
their primary care provider. 
 
A review of the participant’s medical record will be completed to assess for unstable medical or psychiatric 
conditions (e.g., new chemotherapy) that would make it difficult to maintain the participant’s engagement in the 
study. These individuals would also not be appropriate for CBTI under usual care conditions. Individuals 
excluded for unstable conditions will be reassessed 3 months later for eligibility, which is the process that 
would occur in a clinical setting. We will include individuals with stable psychiatric or medical conditions such 
as chronic pain or depression. Finally, we will notify the participant’s hypnotic prescriber at VAGLA or the 
participant’s non-VA provider (via encrypted email) about our intention to taper and discontinue the patient’s 
hypnotic in case there are undocumented clinical indications other than insomnia (see Email to Prescribers). If 
the prescribing physician does not agree with tapering the medication, the individual will not be randomized. 
Participants determined to be ineligible for the study will be notified by mail (see Participant Ineligibility Letter).   
 
Randomization 
Individuals who complete the baseline assessment and meet all inclusion/exclusion criteria will be randomly 
assigned to one of the two intervention groups: MTcap (N=66) or SGT+CBTI (N=66). Both interventions are 
described below. Randomization procedures will follow the CONSORT criteria for randomized trials. Stratified 

Study Protocol   
 
10 
   V 6.16.2023 
randomization will be used to ensure that both groups are balanced in baseline hypnotic drug type half-life (i.e., 
temazepam/zolpidem; alprazolam/lorazepam; clonazepam) and gender. The study statistician will generate the 
stratified randomization sequence. A set of envelopes containing the group assignment will be generated and 
stored in a secure file drawer accessible only authorized staff.  Once final eligibility is determined, the data 
manager will open the next envelope in sequence within the appropriate stratum. 
 
Interventions 
Both interventions will involve 8 sessions provided by a trained cognitive behavioral therapy for insomnia 
(CBTI) interventionist. The intervention period is expected to last approximately 9 weeks (but may be extended 
as described below). Both interventions include a tapering protocol for benzodiazepine use, behavioral therapy 
for insomnia, plus weekly assessment for withdrawal 
symptoms. During week 7 and at the beginning of week 9 
of the intervention, participants will only receive the 
withdrawal symptom assessment (see table to right). 
Participants will receive $25 for attending the 2 withdrawal 
symptom assessments. The actual content and structure 
of the behavioral therapy and tapering protocol will differ 
between the two groups, although the dose reduction 
schedule will be the same for the two groups (described 
below). Intervention sessions will take place in designated, 
private research offices at VAGLA. All interventionist 
sessions will be audio-recorded and a random subset will 
be rated using a structured rating sheet to ensure fidelity to 
the treatment protocol. The interventionist will also 
maintain a session-by-session list of information covered 
and recommendations made. “Progress notes” will be 
maintained by the interventionist and reviewed during 
weekly “intervention meetings.” These processes will 
ensure fidelity over the course of the study and avoid the 
risk of contamination across study arms. 
 
Amendment for telehealth option 
Intervention sessions conducted by VVC 
Participants who receive the intervention sessions by VVC will receive the auto-generated and study-
generated emails described above for the baseline assessments.  The content of the intervention and taper 
schedules used to taper hypnotic use will be identical to the in-person sessions. 
Prior to the first intervention session, the following materials will be mailed to participants:  
• 
Notebook containing education materials for each session 
• 
Sleep diaries for each week 
• 
Blood pressure machine (if participant does not have a blood pressure machine at their home) 
• 
Questionnaires (i.e., CIWA, ISI, ESS questionnaires) completed at sessions    
• 
Postage-paid, self-addressed return envelopes to return questionnaires 
• 
Medication for SGT group: 30-day supply plus Paper Taper Schedule in a sealed envelope to be 
opened at Session 1  
• 
Medication for MTcap group: 3-week supply plus 3 weeks PRN plateau 
• 
Postage-paid, pre-addressed, delivery box to return unused medication. 
 
Additional medication will be mailed to participants over the course of the intervention according to the taper 
schedule for that group. 
 
Amendment for telephone option 
If video connection is not possible due to technical issues (e.g., bandwidth connectivity issues, software 
problems, hardware issues) research staff will conduct the intervention session via telephone.  Staff will follow 
the same protocol as described for VVC visits.   
 
 
Week 
Session 
MTcap  
Group 
SGT+CBTI Group 
1 
1 
Intervention + BWA 
Intervention + BWA 
2 
2 
Intervention + BWA 
Intervention + BWA 
3 
3 
Intervention + BWA 
Intervention + BWA 
4 
4 
Intervention + BWA 
Intervention + BWA 
5 
5 
Intervention + BWA 
Intervention + BWA 
6 
6 
Intervention + BWA 
Intervention + BWA 
7 
 
BWA only 
BWA only 
8 
7 
Intervention + BWA 
Intervention + BWA 
9  
Beginning 
of week 
 
BWA only 
BWA only 
9 
End of 
week 
8 
Intervention + BWA 
Intervention + BWA 
BWA=Benzodiazepine withdrawal assessment (i.e., CIBA-B, vitals, 
ISI, ESS)  

Study Protocol   
 
11 
   V 6.16.2023 
• 
Measures collected during intervention:  
A urine sample will be collected from participants at the first intervention session. The urine sample will be 
tested for benzodiazepines and zolpidem to confirm the participant’s use/nonuse of these hypnotics.   
The following measures will be collected weekly throughout the intervention for participants in both study 
groups. 
Clinical Institute Withdrawal Assessment Scale - Benzodiazepines (CIWA-B):  This 22-item instrument includes 
patient symptoms and clinical observations (e.g., tremor) to assess and monitor the type and severity of 
symptoms of benzodiazepine withdrawal.  
Vital signs: These physical examination measurements will be taken weekly: blood pressure, pulse, respiratory 
rate. 
Insomnia Severity Index (ISI): The ISI is a 7-item instrument that measures perceived severity of insomnia 
symptoms (total score ranges from 0 to 28).  
Epworth Sleepiness Scale (ESS): This 8-item questionnaire assesses general level of daytime sleepiness.  
 
Amendment for telehealth option 
Urine sample: Participants who receive the intervention by VVC/telephone will be asked to go to the VA clinical 
lab to provide a urine sample prior to the first intervention session.  
Vital signs: The interventionist will assess respiratory rate and observe the participant measure their blood 
pressure and pulse via VVC at each session.  
 
Daily sleep and habits diary:  Participants will use the diary to record bedtime, wake time, total sleep time, time 
to fall asleep, time awake at night, number of awakenings, napping, exercise, alcohol use.  Participants in the 
MTcap group only will also record their perceived hypnotic dose taken and their daytime function and sleep 
quality. 
 
• 
MTcap (Masked Taper plus cognitive behavioral therapy-augmented program):  
a. Hypnotic taper protocol: Participants will receive encapsulated hypnotics in a blister taper pack 
prepared by a non-VA compounding pharmacy. Participants will be informed that gradual dose 
reduction will occur during the program, but they will be blinded to the actual dose they receive each 
day.  The planned rate of reduction of hypnotic will be about 25% per week. The final taper pack will 
consist of 4 placebo capsules (nights 1-4) and 3 empty blisters (nights 5-7). This planned rate of taper 
would yield a taper length similar to those reported in other studies, where the average length of taper 
was 49 days (range 6.5 to 84 days).  
 
b.  Cognitive behavioral therapy for insomnia-augmented program: The 8 sessions will incorporate the key 
components of CBTI (sleep restriction, stimulus control, cognitive restructuring, targeted sleep hygiene) 
and CBT targeting hypnotic withdrawal. Using the masked doses as a CBT tool, we will add exercises and 
concepts designed to address and alter expectations for hypnotics. A daily sleep/perceived hypnotic dose 
diary will be used as a tool for challenging expectancies about hypnotics, refining treatment 
recommendations, and adjusting the weekly plan.  
 
• 
SGT+CBTI:  
a. Hypnotic taper protocol: Participants will receive hypnotics in a traditional medication container 
prepared by a non-VA compounding pharmacy. Participants will also receive a printed taper schedule 
(see attached Taper Schedule) that reduces the hypnotic using the same schedule as the MTcap 
group. Each participant will be given a pill cutter so they can cut pills in half or into quarters as directed. 
A printed taper schedule is routinely used in VA clinical practice to assist patients in reducing hypnotic 
use. An exception to this protocol will occur if the prescribed medication is temazepam.  This 
medication only comes in capsule form, so it cannot be cut into halves or quarters.  Consequently, the 
participant will receive two difference strengths of temazepam (e.g., 15mg and 7.5mg) in two separately 
labeled bottles.  Rather than cutting the higher strength capsule in half, participants will take the lower 
strength capsule.  This is the taper method that is used clinically for temazepam.  
 
b. Cognitive behavioral therapy for insomnia: Participants will receive standard CBTI (i.e., stimulus control, 
sleep restriction, targeting maladaptive beliefs about sleep, sleep hygiene, and relaxation techniques), 

Study Protocol   
 
12 
   V 6.16.2023 
and will not be provided with the extra exercises and tools that the MTcap group will receive. The sleep 
diary that participants will complete will be slightly different from the MTcap sleep diary. 
 
• 
Extended taper plan 
We have identified specific situations when the taper plan may need to be modified:  
a. Withdrawal symptoms/extended taper required: The taper may be extended up to a maximum of 16 
weeks if the participant has withdrawal symptoms or cannot tolerate the scheduled taper, based upon 
changes in several of the CIWA-B items and vital signs, along with the patient’s, interventionist’s, and 
study physicians’ judgments. In the MTcap group, an extended taper may be achieved by giving a 
duplicate 7-day blister pack (e.g., plateauing the doses until the participant is ready to move to the next 
blister pack). In the SGT+CBTI group, participants will be instructed to repeat a particular week in the 
printed taper schedule.  Participants will continue to be monitored with weekly CIWA-B, vital signs, and 
the interventionist will review and reinforce key content of the intervention.  
b. Hypnotic dosed as “prn” at baseline: Taper schedules for participants who used their hypnotic “as 
needed” at baseline will be adjusted so that the starting week’s total weekly hypnotic dose does not 
exceed the participants’ total weekly baseline hypnotic dose. 
For the MTcap group, the capsules on the predetermined drug-free days will be filled with an inert 
filler substance.  The participants will still be instructed to take the capsule on a scheduled based 
nightly, not as needed. The use of capsules will ensure that the participant is not exposed to the drug 
more frequently than the baseline exposure. An increase in adherence to the taper protocol is one 
rationale for using capsules filled with inert filler substance rather than instructing participants not to 
take any capsule at all (i.e., similar to oral contraceptive inert pills that are provided in the monthly oral 
contraceptive pill pack). Another rationale for using insert capsules is related to our study’s objective, 
which aims to develop an intervention for reducing placebo effects, such as the effects related to the 
conditioned response of taking the drug and attributing sleep and daytime function—which are known 
to vary from day to day—to the act of taking the pill.  
For the SGT+CBTI (supervised gradual taper + CBTI) group, the paper taper schedule will indicate 
which days of the week the participant should and should not take the hypnotic. For example, Mondays, 
Wednesdays, Fridays, and Saturdays may be deemed drug days, while Tuesdays, Thursdays, and 
Sundays may be deemed drug-free days. The gradual tapering of drug doses on the drug days will 
occur over the two-month period. The drug-free days will be clearly marked on the taper schedule. A 
progressive increase in the number of drug-free days will occur during the taper. 
 
c. More than 1 hypnotic at baseline: Participants who use >1 of the target hypnotics will be tapered off the 
targeted hypnotics simultaneously using two different blister packs.  
 
• 
Procotols for preparation of hypnotics 
 
MTcap group: The blister packs containing the hypnotic will be prepared by Lynn Oaks Compounding 
Pharmacy located in Thousand Oaks, California, which has staff that are experienced in preparing 
medications for research purposes.  Dr. Fung will write prescriptions for the appropriate hypnotic that will 
cover the entire intervention period.  The prescriptions will be sent via encrypted email or fax to the 
pharmacy.  The compounding pharmacy will prepare the blister packs for the intervention period (e.g., 8 
weeks, but could be longer if the participant needs a prolonged taper) and send them via overnight mail or 
courier to the VA Research Pharmacy.  If necessary, the medications will be picked up by research staff 
and transported to the Research Pharmacy.  The research pharmacist will label the blister packs per VA 
protocols. The prescription will be entered into CPRS as a non-VA prescription. 
 
SGT+CBTI group: Dr. Fung will write prescriptions for the appropriate hypnotic that will cover the entire 
intervention period.  The prescriptions will be sent via encrypted email or fax to the pharmacy.  The 
compounding pharmacy will prepare a 30-day supply of the appropriate medication for the participant. The 
medication will be dispensed in a regular prescription bottle and labeled by the pharmacy.  At the end of 
the month, a second 30-day supply of medication will be prepared and dispensed. The medication will be 
sent via overnight mail or courier to the VA Research Pharmacy.  If necessary, the medications will be 
picked up by research staff and transported to the Research Pharmacy.  The prescription will be entered 
into CPRS as a non-VA prescription. 

Study Protocol   
 
13 
   V 6.16.2023 
 
• 
Protocols for distribution of hypnotics 
For both groups, a member of the research team will pick-up the medication bottle or blister packs from the 
VA Research Pharmacy and give it to the participant at the first intervention session. If the participant does 
not come to the appointment, the medication will be returned to the Research Pharmacy. If the Research 
Pharmacy is closed (e.g., the pharmacist has left for the day, is at a meeting), the medication will be stored 
either in a locked safe (located in Building 115, Room 328) or the locked narcotics box in the Clinical 
Research Center (CRC) in Building 500 on the West Los Angeles campus until the Pharmacy reopens or it 
can be given to the participant.   
 
For participants seen on the Sepulveda campus, a research team member will transport the medication via 
personal car to Sepulveda. The medication will be placed in a locked bag and stored in the trunk during 
transport. The medication will be stored in a locked safe in Building 25/Room A137 until the participant 
receives it at the first session. If the participant does not come to the appointment, the medication will be 
returned to the safe.      
 
Amendment for telehealth option 
Medications will be mailed to participants following the same procedures used by the VA pharmacy service. 
Participants will also have the option of picking up the medication from our research staff at the Sepulveda 
VA or West Los Angeles Medical Center. 
 
• 
Care coordination at end of intervention period 
Participants in the MTcap group will be told the benzodiazepine dose that they are taking when they 
complete the intervention (or if they withdraw before the 9-week intervention period).  The primary care 
providers of participants in both groups will be informed of the final medication regimen, so patients can 
continue to be monitored for withdrawal, if necessary.   
 
At the last session of the intervention, the interventionist will use a debriefing script (see attached 
Debriefing Script) to inform MTcap participants of the actual doses that they were taking over the 9-week 
intervention. Participants will be given the taper schedule that the SGT+CBTI group followed (see attached 
Taper Schedule) unless there was a plateau in the tapering, in which case participants will be shown a 
revised taper schedule.  The interventionist will tell participants the dose that they are currently taking and 
will review the last week’s sleep diary to compare what participants thought they were taking with the actual 
dose.  Participants will be given an opportunity to ask questions about the research, will be asked if they 
agree to allow the investigator to use the data collected up to that point in the study (additional data will be 
collected at post-treatment, and 6-months), and will be given contact information for the interventionist and 
Dr. Fung.   
 
Follow-up assessments 
We will encourage participants to complete assessments even if they elect not to complete the intervention. All 
follow-up assessments will be conducted by research staff who are blinded to group assignment. 
 
• 
Post-treatment assessment 
The post-treatment assessment will begin on the same day that the participant completes session 8 of either 
intervention.  At the end of session 8, a participant will be provided with an actigraph to wear at home for 1 
week and a sleep and medication diary to complete. When the participant returns the actigraph and diary after 
1 week, he/she will be administered selected questionnaires included in the baseline assessment. In addition, 
a urine sample will be collected to confirm participants’ self-report of hypnotic discontinuation. Participants will 
also be given a six-month fall log to record any falls they experience during the period between the post-
assessment and the six-month follow-up assessment. The CURES database will also be queried to obtain data 
about prescriptions for controlled medications. Participants who complete the post-treatment assessment will 
receive $50 for their travel and time.  
 
• 
Six-month follow-up   
The six-month assessment will occur six-months after session 8 is completed (or was scheduled to be 
completed if a participant drops out of the intervention).  This assessment will include 2 visits to the study site. 

Study Protocol   
 
14 
   V 6.16.2023 
The measures collected will be identical to the post-treatment assessment. At visit 1, the participant will receive 
an actigraph to wear at home for 1 week, a sleep and medication diary to complete, and selected 
questionnaires will be administered. At visit 2, the participant will return the actigraph, diary, six-month fall log, 
and will complete additional questionnaires and provide a urine sample.  The CURES database will also be 
queried to obtain data about prescriptions for controlled medications. Participants who complete the 6-month 
follow-up will receive $50 for their travel and time. 
 
Amendment for telehealth option 
Post-treatment follow-up assessment (begins at end of session 8) 
Prior to intervention session 8 VVC visit, participants will receive by mail/pick-up the following items: 
• 
Wrist actigraph 
• 
Sleep diary 
• 
Questionnaire packet 
• 
Medication log 
• 
Fall log 
• 
Postage-paid return, insured Return Box to return the study materials (e.g.,actigraph) 
Participants will also be instructed to go to the VA clinical laboratory to provide a urine sample. 
 
 
At the end of session 8, the participant will be instructed to put on the actigraph to wear at home for 1 week 
and to complete the sleep and medication diary each day of that week.  
One week later, a VVC post-treatment assessment visit will occur.  At that visit, the participant will be 
administered selected questionnaires included in the baseline assessment. Participants will also be instructed 
to record any falls they experience over the next six months in the fall log.  Participants will mail/deliver the 
actigraph and sleep diary back to the study office. 
 
Six-month follow-up assessment 
A few days prior to the VVC visit, participants will receive by mail/pick-up the following items: 
 
• 
Wrist actigraph 
• 
Sleep diary 
• 
Questionnaire packet 
• 
Medication log 
• 
Postage-paid return, insured Return Box to return the study materials (e.g., actigraph, sleep diary and 
fall log) 
 
Participants will also be instructed to go to the VA clinical laboratory to provide a urine sample. 
 
Participants will wear the actigraph for 7 days and nights, complete the sleep diary, and answer the 
questionnaires over the course of two VVC visits.   
 
Amendment for telephone option 
If video connection is not possible due to technical issues (e.g., bandwidth connectivity issues, software 
problems, hardware issues), research staff will conduct the follow-up visits via telephone.   
 
Amendment for abbreviated mailed follow-up questionnaire  
When a participant is unable to be contacted (e.g., due to a non-working phone number) or refuses to 
complete a follow-up assessment by video or telephone, the participant will be mailed an abbreviated 
assessment that includes three questionnaires from the approved follow-up assessment (i.e., ISI, Dbase-16, 
and sleeping pill use). 
 
Amendment to add giftcards as an alternative patient compensation  
The giftcards will serve as alternative subject payment if the subject did not receive original VA issued check 
compensation after a completed study visit. This addition to the protocol was added to reduce delayed 
payment compensation and maintain study integrity. 
 
 

Study Protocol   
 
15 
   V 6.16.2023 
• 
Follow-up for Missed Appointments  
Participants who miss a study appointment will be telephoned by research staff on the day of the missed 
appointment. If the participant does not return the call within 10 days of the missed appointment, a letter will be 
sent that encourages the participant to contact the research office (see Missed Appointment Letter). If a 
participant has not returned an actigraph or Watch-PAT device, the letter will also include a paragraph about 
the importance of returning the device.  If the participant does not return the device after 10 days from the date 
of the first letter, a second letter will be sent that explains that failure to return the device requires staff to 
submit a missing equipment report to VA police (see Failure to Return Device Letter).        
 
Potential Risks and Safety Plan 
 
• 
Benzodiazepine withdrawal symptoms: Symptoms are not common with withdrawal of low doses of 
benzodiazepines, but could include dizziness, anxiety, depression, and insomnia. The proposed 
intervention has a similar risk level to behavioral/ pharmacological strategies recommended by healthcare 
providers to adults as part of routine clinical care. Based on our pilot data and our team’s collective clinical 
experience with low-dose hypnotic discontinuation, withdrawal symptoms that warrant protocol changes 
are uncommon. To reduce the risk of severe withdrawal symptoms, adults at high risk of complicated 
withdrawal or on high benzodiazepine doses (based on comorbidities, current prescriptions, and answers 
to assessment questions) will not be randomized to receive the intervention.  Participants will be monitored 
weekly with the Clinical Institute Withdrawal Assessment-Benzodiazepine [CIWA-B] instrument and with 
weekly vital signs. If the participant is found to have mild symptoms of withdrawal based on select items 
from the CIWA-B or on mild changes in vital signs, a study physician (e.g., Drs. Fung or Alessi) and the 
participant may decide to plateau the taper until the participant is ready to continue with the dose taper. If 
participants are found to have moderate, severe, or very severe scores on select items in the CIWA-B, or 
moderate or severe vital sign changes, or have worsening severed insomnia, the study physicians will 
discuss the patient’s symptoms with a staff psychiatrist to determine whether the changes to the taper 
schedule are needed (including increasing or plateauing the dose) and whether the patient needs 
additional clinical evaluation. If the patient needs clinical evaluation, the participant will be escorted to the 
outpatient clinic or for life-threatening emergencies at our facility, we will call 911. 
 
Amendment for telehealth option 
If a participant needs clinical evaluation during a VVC appointment, staff will advise the participant to seek 
medical care locally at the nearest emergency department, or for life-threatening emergencies, we will call 911. 
 
• 
Confusion about duplicate hypnotic prescriptions: Participants may not understand that the hypnotic 
provided by the study (in blister packs or medication bottle) replaces the hypnotic that they were previously 
taking. This could result in participants taking both prescriptions at the same time, which would result in a 
higher dose than prescribed, and possible side-effects (e.g., daytime sleepiness, dizziness).  To avoid 
confusion about duplicate hypnotic prescriptions, participants in both groups will be asked to bring all their 
medications to the first intervention session.  The interventionist will identify the hypnotic that will be 
tapered and will place the bottle in a sealed envelope.  A label will be affixed to the outside of the envelope 
that states, “Do not take this medication during the 8-week SWITCH study unless instructed by the study 
staff.” The interventionist will explain that the participant will receive the same hypnotic either in a new 
medication bottle or in the blister packs and should put the old prescription in the sealed envelope in a safe 
location.  
 
• 
Increased daytime sleepiness: Adjustments to the participant’s sleep habits may result in some initial 
daytime sleepiness. Daytime sleepiness will be monitored during each weekly in-person intervention 
assessment with the Epworth Sleepiness Scale, and participants with increased daytime sleepiness will be 
counseled on the possibility of impaired cognition and increased fall and motor vehicle crash risk. If 
excessive daytime sleepiness is thought to be due to study-related sleep restriction (as opposed to, for 
example, a newly-prescribed medication from the individual’s physician), the prescribed sleep schedule will 
be adjusted.  
 
• 
Mental discomfort: The minor risks associated with completion of the questionnaires include tediousness, 
fatigue, and/or mental discomfort answering the items. Participants could also find wearing the actigraph 

Study Protocol   
 
16 
   V 6.16.2023 
and home sleep apnea testing device (e.g., WatchPAT device) to be annoying or uncomfortable. To reduce 
the risk of mental discomfort among participants, research staff will be trained to recognize discomfort in 
participants, and they will be trained to remind participants of the voluntary nature of the research and the 
option for participants to decline participation in any portion of the research project. 
 
• 
Falling during one-leg balance test: Participants could lose balance and fall during the one-leg balance test. 
To reduce the risk of falling during the one-leg balance test, research staff will place a gait belt around 
participants. For participants who use mobility aids, two research staff will perform the testing and 
additional steps such as placing a walker around the participant may also be employed. 
 
• 
Skin irritation: The sensors worn for one night as part of the home sleep apnea testing device (e.g., 
WatchPAT device) and the actigraph wrist band worn for 7 days may cause skin irritation or an allergy. We 
have extensive experience using wrist actigraphy and the home sleep apnea testing devices such as the 
WatchPat system, and have chosen these devices because they are well-tolerated by participants. They 
are also substantially less burdensome than other objective methods of recording sleep (i.e., requiring the 
participant to spend a night in a sleep laboratory). Research staff will carefully review with participants 
potential skin problems associated with wearing the wrist actigraph and the home sleep apnea testing 
device sensors. Participants will be told to remove the device if they have any significant discomfort or any 
evidence of skin injury. Participants will have access to a research staff person, in case they have 
questions or concerns about the equipment. In addition, the company which makes the WatchPAT device 
has a 24-hour advice line that also provides troubleshooting support. Our monitoring devices are checked 
regularly to insure safe and proper operation. Dr. Fung (PI) will be notified immediately of any significant 
discomfort experienced by study participants. 
 
• 
Confidentiality and privacy breach: There is risk of breach of privacy via unintentional disclosure of 
Protected Health Information, which could lead to embarrassment and fraud, which in turn could have 
negative financial impact on participants. To ensure confidentiality of the research data collected, all 
participants will have a unique identification number assigned that is not based on any identifying 
information. This identification number will be used for all computer databases, which will be stored behind 
a firewall on the VAGLA Health Services Research & Development (HSR&D)-managed server, as well as 
for hard copy data collection forms. Access to these databases and hard copy forms will be limited to the 
study’s approved research staff and will not be transmitted. Research hypnotic tracking logs (that use 
subject identification numbers) will be maintained to ensure that all hypnotics that are prepared, dispensed, 
and disposed (if unused) are accounted for at all times. These hypnotic tracking logs will be shared with the 
VA research pharmacy (via a shared folder located behind a firewall). Consent forms and hard copies of 
data forms will be stored in locked file cabinets in locked offices with access limited to approved research 
staff, in the VAGLA Geriatric Research, Education and Clinical Center (GRECC) research offices. 
Electronic lists of names and contact information will be kept separate from other data in limited access 
folders on the VAGLA HSR&D-managed secure server behind a VA firewall. Data will be destroyed 
according to the Records Control Schedule. 
 
Amendment for telehealth option 
Video/telehealth Standard Practices  
VA Video Connect (VVC) will be the preferred platform that will be used for video interactions with research 
participants. In the event that VVC fails, we will follow current VA guidance and use currently approved 
patient-facing platforms.  
 
We will use standard video/telehealth practices including verifying the participant’s identity, inquiring 
whether they have privacy during the visit, as well as obtaining their location and an emergency contact, in 
case of an emergency during the visit. 
 
Our overall procedure for monitoring and reporting study-related adverse events includes:  
Step 1: If a participant reports or monitoring reveals a study-related adverse event, research staff will report 
this to the Principal Investigator (Dr. Fung). When Dr. Fung is unavailable, Dr. Alessi (study co-investigator) 
will be contacted. The research staff will closely adhere to VAGLA emergency reporting policies and 
procedures. 

Study Protocol   
 
17 
   V 6.16.2023 
Step 2:  If indicated, Dr. Fung will speak with the participant to determine the severity and likely cause of 
the concern.  If medical examination is needed and the situation is non-emergent, the participant will be 
advised to go to the VA outpatient clinic.   
Step 3: Dr. Fung will report the event to the IRB and will make a determination whether study protocols 
should be modified for that participant, whether the participant should be withdrawn from the study, or 
whether the study protocols should be modified overall.  
Step 4: All concerns reported by research staff will be documented, whether they appear to be study-
related, and will be reviewed monthly by Dr. Fung. 
If a participant reports a high level of mental distress, or discloses suicidal ideation during the interview 
process, research staff will follow these steps: 
Step 1: Research staff will immediately contact Dr. Fung (or another immediately available clinician) who 
will do an assessment. If relevant, the participant will be provided with the telephone number for the VHA 
suicide prevention hotline or other local suicide prevention resources. 
Step 2:  If needed, the participant will be taken by research staff to the mental health or primary care 
outpatient clinic for evaluation and/or treatment. For all life-threatening emergencies at our facility, we call 
911 and notify VA police. 
Step 3: As above, events will be reported to the IRB and a determination will be made about the protocol 
and the appropriateness of the participant continuing in the study. 
 
Primary Analysis Plan  
We plan to randomize 132 individuals, of whom we expect 13% to drop out (i.e., fail to complete assessments) 
by 6-months, yielding N=114 participants with complete data (~ 57 per group). We base this drop-out on our 
completed study (Alessi VA Merit 08-295). We will include terms for stratification characteristics and covariates 
for baseline pain intensity, PHQ-9, and opioid use in all of the models. All analyses below assume α=0.05, 
power=0.80, two-sided hypothesis tests, and intention-to-treat approach. Effect sizes are in the measure’s 
natural units and Cohen's d (large=.8; medium=.5; small=.2).  
 
• 
(H1a) Participants who receive MTcap will have increased likelihood of hypnotic discontinuation post-
treatment and at 6 months follow-up compared with those who receive SGT+CBTI: Hypnotic 
discontinuation (yes=1/no=0) will be regressed on treatment group assignment (MTcap vs. SGT+CBTI) in 
two logistic regression models (post-treatment and 6 months follow-up). Sample size calculations establish 
that 114 participants will be adequate to detect a difference of 21% to 26% between the MTcap and 
SGT+CBTI groups, depending upon the discontinuation percentage of the SGT+CBTI group (59% to 63% 
at follow-up57;102 in prior studies). In our feasibility study, 100% discontinued hypnotics post-treatment. We 
will use multiple imputation.  
• 
(H1b) Participants who receive MTcap will use less hypnotic medication post-treatment and at 6 months 
follow-up compared with those who receive SGT+CBTI: Two outcomes will be assessed: frequency (i.e., 0 
to 7 days used) and quantity (i.e., average daily dose in diazepam milligram equivalents66). For each 
outcome, we will fit a 2 (group) by 3 (time) general linear mixed model.66 Interaction terms will be used to 
assess the change in the outcome (baselinepost-treatment, baseline6 months) for MTcap vs. 
SGT+CBTI. Power Analysis: We use statistics from our recent study, which found a baseline to 6-month 
correlation of r=0.83 (95% CI=0.77-0.88) and a standard deviation (SD) of 1.94 for a similar outcome 
measure—“days used of medications commonly used for insomnia” (0 to 7 days used). Assuming r=0.83 
and n=57 per group, we could detect a treatment effect of 0.60 (Cohen's d=0.30) (i.e. a difference of 6/10ths 
of a day between the groups). Assuming r=0.77 (i.e., using the LCL), we could detect a treatment effect of 
0.70 days (Cohen's d=0.36). If we disregard data from our recent study, power calculations still show that 
we could detect a treatment effect of 1.02 days (Cohen's d=.53; i.e., detect a difference of 1 day between 
groups). For quantity of use, power calculations indicate that we could detect a treatment effect of d=.53 
(medium effect).  
• 
(H2) Participants who receive MTcap will have lower Insomnia Severity Index scores at 6 months follow-up 
compared to SGT+CBTI: We will fit a general linear mixed model, and an interaction term will assess the 
change in ISI from baseline to 6 months for MTcap vs. SGT+CBTI. Power Analysis: Our prior research 
shows an ISI SD=5.3 and r=0.39 (95% CI=0.24-0.52) between baseline ISI and 6 month follow-up ISI. 
Assuming this correlation and a sample size of N=57 per group, the study could detect an effect as small 
as 3.1 units on the ISI (or a Cohen's d=.58). Assuming r=0.24 (i.e., using the LCL), we could detect an 
effect as small as 3.43 units on the ISI (or a Cohen's d=.65). An effect of 4.0 units on the ISI has been 

Study Protocol   
 
18 
   V 6.16.2023 
determined to be clinically-meaningful in prior research,103 which means that the proposed study would be 
able to detect effects that are clinically-meaningful (as well as effects that smaller than clinically-
meaningful); both of these power analyses suggest that the study could detect effects that are between 
medium and large effects. 
• 
(H3) Dysfunctional Beliefs and Attitudes About Sleep (DBAS) – Medication Scale ratings will improve 
compared to SGT+CBTI post-treatment and at 6 months follow-up: We will fit a 2 (group) by 3 (time) 
general linear mixed model. Interaction terms will be used to assess the change in DBAS medication items 
(baselinepost-treatment, baseline6 months) for MTcap vs. SGT+CBTI group. Power Analysis: Our prior 
research shows a DBAS-16 SD= 2.1 and r=0.55 (95% CI=0.39,0.64) between baseline DBAS and 6-month 
follow-up DBAS. Assuming this correlation and a sample size of N=57 per group, the study could detect an 
effect size of d=0.50, which is a difference of 1.1 units on the DBAS-16. Assuming r=0.39 (the LCL), we 
could detect an effect size of d=.58, corresponding to a 1.2 unit change.  
 
Secondary Analysis Plan (H4) 
We will test whether MTcap improves cognition (DSS, Symbol Copy; Trails A & B) and balance (One-leg 
balance) at post-treatment and 6-month follow-up, using general linear mixed model (see Hypothesis 3 above). 
Effect size calculations: For the most pessimistic case—no correlation between these measures at the two 
time points—a post-test only analysis could detect a difference of d=0.52. 
 
Exploratory Analysis Plan (E1)  
We will describe the frequency of falls in each arm. We will test whether MTcap is associated with not falling, 
using logistic regression (dependent variable [DV] is fall [binary]), which will be predicted as a function of 
treatment group assignment. E2: Mediation analyses to elucidate the relationship between insomnia severity, 
hypnotic use, and balance will be conducted using a statistical macro developed by UCLA, which 
simultaneously tests for the associations of the independent variable (IV; ISI) on the DV (balance), IV on the 
mediator (hypnotic dose in diazepam equivalents), and IV (ISI) plus mediator (hypnotic dose) on DV (balance) 
(Sobel, Goodman, and Goodman II tests). Similar mediation analyses (using a Stata user written command for 
binary mediation) will be performed for the DV, history of fall. 
 
Amendment: We will conduct the same analyses above, but with the addition of data from participants 
recruited and seen at the UCLA Health site. These data will be transferred in a limited data set from UCLA 
Health to VA Greater Los Angeles under an approved data use agreement. 
 
 
 

Study Protocol   
 
19 
   V 6.16.2023 
Project Timeline 
 
 

Study Protocol   
 
20 
   V 6.16.2023 
References 
 
 3.  Ford ES, Wheaton AG, Cunningham TJ et al. Trends in outpatient visits for insomnia, sleep apnea, and 
prescriptions for sleep medications among US adults: findings from the National Ambulatory Medical Care 
survey 1999-2010. Sleep 2014;37:1283-1293.PMC4096197 
 4. Mustafa M, Erokwu N, Ebose I et al. Sleep problems and the risk for sleep disorders in an outpatient 
veteran population. Sleep Breath 2005;9:57-63. 
 5. Rossat A, Fantino B, Bongue B et al. Association between benzodiazepines and recurrent falls: a cross-
sectional elderly population-based study. J Nutr Health Aging 2011;15:72-77. 
 6. Allain H, Bentue-Ferrer D, Polard E et al. Postural instability and consequent falls and hip fractures 
associated with use of hypnotics in the elderly: a comparative review. Drugs Aging 2005;22:749-765. 
 7. Zhong G, Wang Y, Zhang Y et al. Association between Benzodiazepine Use and Dementia: A Meta-
Analysis. PLoS One 2015;10:e0127836.PMC4446315 
 8. Tsunoda K, Uchida H, Suzuki T et al. Effects of discontinuing benzodiazepine-derivative hypnotics on 
postural sway and cognitive functions in the elderly. Int J Geriatr Psychiatry 2010;25:1259-1265. 
 9. Barker MJ, Greenwood KM, Jackson M et al. Persistence of cognitive effects after withdrawal from long-
term benzodiazepine use: a meta-analysis. Arch Clin Neuropsychol 2004;19:437-454. 
10. Darker CD, Sweeney BP, Barry JM et al. Psychosocial interventions for benzodiazepine harmful use, 
abuse or dependence. Cochrane Database Syst Rev 2015;5:CD009652. 
11. Vicens C, Fiol F, Llobera J et al. Withdrawal from long-term benzodiazepine use: randomised trial in family 
practice. Br J Gen Pract 2006;56:958-963.PMC1934057 
12. Perlis ML, McCall WV, Jungquist CR et al. Placebo effects in primary insomnia. Sleep Med Rev 
2005;9:381-389. 
13. Winkler A, Rief W. Effect of Placebo Conditions on Polysomnographic Parameters in Primary Insomnia: A 
Meta-Analysis. Sleep 2015;38:925-931.PMC4434559 
14. Perlis M, Grandner M, Zee J et al. Durability of treatment response to zolpidem with three different 
maintenance regimens: a preliminary study. Sleep Med 2015;16:1160-1168.PMC4709332 
15. Sangha O, Stucki G, Liang MH, Fossel AH, Katz JN. The Self-administered Comorbidity Questionnaire: A 
new method to assess comorbidity for clinical and health services research. Arthritis & Rheumatism 
2003;49:156-163. 
16. Bastien CH, Vallieres A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for 
insomnia research. Sleep Med 2001;2:297-307. 
17. Buysse DJ, Reynolds CFI, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new 
instrument for psychiatric practice and research. Psychiatry Res 1989;28(2):193-213. 
18. Morin CM, Vallieres A, Ivers H. Dysfunctional beliefs and attitudes about sleep (DBAS): validation of a brief 
version (DBAS-16). Sleep 2007;30:1547-1554. 
19. Horne JA, Ostberg O. A self-assessment questionnaire to determine morningness-eveningness in human 
circadian rhythms. Int J Chronobiol 1976;4:97-110. 
20. Krakow B. Nightmare complaints in treatment-seeking patients in clinical sleep medicine settings. Sleep 
2006;2:1313-1319. 
21. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J. Restless legs syndrome: 
diagnostic criteria, special considerations and epidemiology. A report from the restless legs syndrome 
diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003;4:101-119. 
22. Silva GE; Vana KD; Goodwin JL; Sherrill DL; Quan SF. Identification of patients with sleep disordered 
breathing: comparing the Four-Variable screening tool, STOP, STOPBang, and Epworth Sleepiness 
Scales. J Clin Sleep Med 2011;7(5):467-472. 
23. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 
1991;14:540-545. 
24. Keller S, Bann CM, Dodd SL, Schein J, Mendoza TR, Cleeland CS. Validity of the brief pain inventory for 
use in documenting the outcomes of patients with noncancer pain. Clin J Pain 2004;20:309-318. 
25. Skevington SM, Lotfy M, Connell KA. The World Health Organization’s WHOQOL-BREF quality of life 
assessment: Psychometric properties and results of the international field trial. A report from the WHOQOL 
Group. Quality of Life Research, 2004; 13:299–310. 
26. Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): 
the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J 
Clin Psychiatry 1998;20:22-23.  

Study Protocol   
 
21 
   V 6.16.2023 
27. Cameron, R. P., & Gusman, D. (2003). The primary care PTSD screen (PC-PTSD): development and 
operating characteristics. Primary Care Psychiatry, 9(1), 9-14. 
28. Spitzer RL, Kroenke K, Williams JB et al. A brief measure for assessing generalized anxiety disorder: the 
GAD-7. Arch Intern Med 2006;166:1092-1097. 
29. Kroenke K, Spitzer RL, Williams JBW. Validity of a brief depression severity measure. J Gen Intern Med 
2001;16:606-613. 
30. Humeniuk, R., Ali, R., World Health Organization, & ASSIST Phase II Study Group. (2006). Validation of 
the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and pilot brief intervention 
[electronic resource]: A technical report of phase II findings of the WHO ASSIST Project. 
31. Reitan RM. Trail Making Test: Manual for Administration and Scoring. Tucson, Arizona: Reitan 
Neuropsychology Lab, 1992. 
32. Joy S, Kaplan E, Fein D. Speed and memory in the WAIS-III Digit Symbol--Coding subtest across the adult 
lifespan. Arch Clin Neuropsychol 2004;19:759-767. 
33. Cockrell JR, Folstein MF. Mini-Mental State Examination (MMSE). Psychopharmacol Bull. 1988;24(4):689-
92 
34. Michikawa T, Nishiwaki Y, Takebayashi T et al. One-leg standing test for elderly populations. J Orthop Sci 
2009;14:675-685.DBEP 
35. Busto UE, Sykora K, Sellers EM. A clinical scale to assess benzodiazepine withdrawal. J Clin 
Psychopharmacol 1989;9:412-416. 
36. Baillie AJ, Mattick RP. The benzodiazepine dependence questionnaire: development, reliability and validity. 
Br J Psychiatry 1996;169:276-281. 
37. Devilly GJ, Borkovec TD. Psychometric properties of the credibility/expectancy questionnaire. J Behav 
Ther Exp Psychiatry 2000;31:73-86. 
57. Morin CM, Bastien C, Guay B et al. Randomized clinical trial of supervised tapering and cognitive behavior 
therapy to facilitate benzodiazepine discontinuation in older adults with chronic insomnia. Am J Psychiatry 
2004;161:332-342. 
66. Voshaar RC, Gorgels WJ, Mol AJ et al. Tapering off long-term benzodiazepine use with or without group 
cognitive-behavioural therapy: three-condition, randomised controlled trial. Br J Psychiatry 2003;182:498-
504. 
102. Baillargeon L, Landreville P, Verreault R et al. Discontinuation of benzodiazepines among older insomniac 
adults treated with cognitive-behavioural therapy combined with gradual tapering: a randomized trial. CMAJ 
2003;169:1015-1020.PMC236226 
103. Garland SN, Carlson LE, Stephens AJ et al. Mindfulness-based stress reduction compared with cognitive 
behavioral therapy for the treatment of insomnia comorbid with cancer: a randomized, partially blinded, 
noninferiority trial. J Clin Oncol 2014;32:449-457