A Randomized, Open Label, Sleep Hygiene Controlled 6-Week Study to Compare the Efficacy of Four (CBT-I, FOA, Combined CBT-I and FOA and Sleep Hygiene) Different Behavioral Approaches for the Treatment of Adult Subjects With Insomnia
Phase: NA
Conditions: Primary Insomnia
Sponsor: Pacific Institute of Medical Sciences

                                                                                                                                             
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1.0                                                        TITLE PAGE 
 
 
                                                                    Puget Sound Psychiatry Center 
10634 E. Riverside Drive, Suite 130 
Bothell, WA. 98011 
 
                                  
 
“A Randomized, Open Label, Sleep Hygiene Controlled 6-Week 
Study to Compare the Efficacy of four (CBT-I, FOA, Combined 
CBT-I and FOA and Sleep Hygiene) Different Behavioral 
Approaches for the Treatment of Adult Subjects with 
Insomnia” 
 
PSPC-17-01 
NCT- 03461666 
                              
 
 
 
 
Protocol Date: 02-12-2018 
Version 1.2 
 
 
 
 
 
 
 
Confidentiality Statement: 
 
This document is the property of Puget Sound Psychiatry Center (PSPC), Bothell WA and may 
not–in full or part–be passed on, reproduced, published, distributed, or submitted to any 
regulatory authority without the express written permission of PSPC. 
 
 
 
 
 
 
 
 

2 
2.0                           SYNOPSIS AND SCHEDULE OF EVALUATIONS 
 
 
 
CLINICAL STUDY SYNOPSIS: Study PSPC-17-01 
Study Number 
PSPC-17-01 
Title of Study 
A Randomized Open Label, Sleep Hygiene Controlled 6-Week Study 
to Compare the Efficacy of four (CBT-I, FOA, Combined CBT-I and 
FOA and Sleep Hygiene) different Behavioral Approaches for the 
Treatment of Adult Subjects with Insomnia. 
 
Study Center (Country) 
Puget Sound Psychiatric Center, Bothell, WA 98011(United States) 
Development Phase 
Prospective Study 
 
Objective 
The current study seeks to evaluate and compare the effectiveness 
of (1) cognitive behavior therapy for insomnia [CBT-I], (2) focus of 
attention [FOA], (3) a combination of cognitive behavior therapy 
for insomnia and focus of attention, and (4) a sleep hygiene control 
intervention.   
 
Methodology 
Allocation: Randomized (1; 1; 1; 1)  
Intervention Model: Parallel Assignment 
Primary Purpose: Treatment 
 
Number of Patients 
40/group or 160 totals. It is estimated that 320 prospects will need to 
be screened in order to have 40 per group for a total of 160 
participants. 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                             
1 
Diagnosis and Main 
Criteria for Inclusion. 
 
Male and female outpatients who are 18 or older to 72 years. Insomnia 
Severity Index > or = 10 
Meet diagnostic criteria for Insomnia Disorder per DSM-5 Willing 
and able to sign Informed consent form Not planning on moving 
away from the area for the subsequent 12 weeks. 
 
Exclusion Criteria 
 
 
 
 
 
 
Participants who answer “yes” to any of the following will be 
excluded: 
Females who are lactating or who are pregnant  
Night shift workers, and individuals who nap 3 or more times per 
week over the preceding month  
Consumption of caffeine beverages (i.e. tea, coffee, or cola) 
comprising usually more than 5 cups or glasses per day  
Participation in another trial for insomnia 
Persons unable to complete the study questionnaires and 
psychological tests 
Persons who are unable to participate for the entire duration of the 
study, or in the opinion of the investigators, are likely to be non-
compliant with the obligations inherent in the trial participation 
Persons self-describing with severe anxiety or severe depression 
(BDI score of 29 or higher) or severe anxiety (BAI score of 36 or 
higher). 
Persons with a history of epilepsy, seizures, or dementia  
Any significant, severe or unstable, acute or chronically 
progressive medical or surgical condition  
Serious head injury or stroke within the past year 
Current alcohol or substance abuse/dependence (must have >90 
days of sobriety) 
Presence of other neurological disorders (e.g., multiple sclerosis, 
Parkinson's Disease) 
Presence of an untreated or unstable medical or psychiatric 
comorbid condition (e.g., major depressive disorder or psychotic 
disorder requiring admission within the last two years).  People 
using psychotropic medication, hypnotic or sedative medications 
may be included if they are on a stable dosage for the last 2 
months prior to the study, if the dose remains stable throughout 
the study, and if the medication is judged to not interfere with the 
study outcomes. 
Currently on medications known to produce insomnia (e.g., 
stimulants) 
Sleep apnea (AHI >15) or previous diagnosis of sleep apnea???   
Study participants who use a continuous positive airway 
pressure (CPAP) device for sleep apnea will be eligible for 
participation if they are below the apnea/hypopnea cutoff 
while using CPAP and agree to use the device during study 
participation. 
 
 

2 
Test Product, Dosage, and 
Mode of Administration 
Behavioral intervention, Six sessions, one hour each.  In person. 
 
Duration of Treatment 
Treatment involves six consecutive weekly sessions. The study 
also includes 3 month, 6 month and 12 month follow-up 
assessment. 
 
Reference Therapy, 
Dosage, and Mode of 
Administration 
Cognitive Behavior Therapy for Insomnia (CBT-I) 
Focus of Attention (FOA) 
Combined CBT-I and FOA 
Sleep Hygiene 
Six sessions, one hour each, in person. 
Criteria for Evaluation 
 
Primary Endpoint 
The primary end point is completion of 6 treatment sessions and 
completion of the 3 month, 6 month and 12 month follow-up 
assessment.  Improvement of insomnia outcome is measured by 
Self Report Sleep Measures (SRSM). 
Key Secondary Endpoint 
The Secondary end point is improvement outcomes. 
 
Additional Endpoints 
Safety Population: will include all randomized subjects who meet 
eligibility criteria and meet with their treatment provider for 
session 1. 
Intent-to-Treat Population: will include all subjects who meet 
with their treatment provider for session 1 and for whom the 
treatment provider determines the subject meets diagnostic criteria 
for 780.52 Insomnia Disorder. 
Pre-Protocol (PP) Population: will include all subjects who 
complete the 6 sessions of treatment as well as the 3 month, 6 
month and 12 month follow up assessment.  It is estimated that 
80% of those who complete session 1 will complete session 6.  It 
is estimated that 80% of those who complete session 6 will 
complete the 3 month, 6 month and 12 month follow up 
assessments.  This will result in 25 participants who will have 
completed the entire study 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                             
1 
 
 
Pharmacogenetics 
Sampling 
There are no pharmacogenetics samplings.  
 
Health Outcomes 
 
Safety Measures 
In general the potential risks for participants are minimal.  The 
treatment approaches involved in related studies have been 
shown to be a safe procedure and in most of the published 
studies people who underwent these procedures did not report 
any harmful effects.   
It is nonetheless possible participant (s) may experience some 
discomforts during the treatment.  These may include temporary 
decrease in time asleep and accompanying daytime drowsiness.  
Some people may become anxious while initially following the 
treatment procedures, with increased worry about their sleep 
difficulty.  Anxiety and worry about sleep difficulty are in fact 
common among persons with insomnia.  Therefore identifying 
and addressing these possibilities will be directly addressed 
during the treatment, and participants will be given guidance 
about what to expect and how to manage should these 
discomforts occur. 
Persons with certain medical illnesses, certain psychiatric 
illnesses or other sleep disorders may be at increased potential 
risk of exacerbation of that illness.  This is a possibility for 
participants with epilepsy, bipolar depression, parasomnia, 
obstructive sleep apnea or other illnesses which have excessive 
daytime sleepiness as a feature of the parent disorder.  The 
participant may (or may not) be assigned to a treatment which 
involves sleep restriction.  Sleep loss through sleep restriction 
may 
1) lower the threshold for seizures in persons with 
epilepsy; 
2)  precipitate mania in bipolar participants; 
3) exacerbate parasomnias; 
prevent adequate ventilation in patients with obstructive 
sleep apnea; and/or aggravate the day time somnolence 
to the point where it is no longer safe for the participant 
to drive, operate machinery and/or make judgments that 
adequately promote their own and/or the safety and 
well-being of others. 
The risk is generally higher when these illnesses are untreated.  
Prospective participants treated for any of these illnesses and 
interested in participating must have the written approval of 
their treatment provider in order to be eligible.  
Prospective participants will be screened and informed of these 
potential risks.  
If any of these risks (1-5 above) occur during the study, the 
participant will be asked to immediately discontinue the sleep 
restriction, and an alternative treatment not involving sleep 

2 
restriction will be offered.  The participant will also have the 
option of discontinuing the treatment if they prefer this to 
proceeding with the alternative treatment which does not 
involve sleep restriction. 
 
Pharmacokinetic 
Sampling 
There are no pharmacokinetic samplings. 
 
Statistical Analysis              Repeated measures analysis of variance (ANOVA)                        
will be used to test Hypotheses 1, 2 and 3.                                      
Chi square will be used to test Hypothesis 4.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                             
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                SCHEDULE OF EVALUATIONS: Study PSPC-17-01 
 
 
(GMS) Goal Motivation Scale; (GMS-I) Goal Motivation Scale-Insomnia, Beck Depression Inventory (BDI); Beck Anxiety Inventory 
(BAI); Insomnia Severity Index (ISI); Self Report Sleep Measures (SRSM); Weekly Sleep Log (WSL);                             
Clinical Global Impression - Improvement (CGI-I), Clinical Global Impression – Severity scale (CGI-S)  
Quality of Life Enjoyment and Satisfaction (Q-LES), End of Treatment (EOT)/Early Termination (One week F/U): (ET) 
Columbia suicide severity rating scale (C-SSRS); Baseline Visit (BV) 
 
 
Screening 
Randomized, Open label, 
sleep  Hygiene Controlled 6 
Week  study 
EOT/
ET (1 
week 
F/U) 
Safety Follow up Period 
 
Visit # 
1 
(BV)/
2 
3 
4 
5 
6 
7        8 
9 
11 
   10 
Study Day  
Weeks/Months  
up to 
1W 
2W 
3W 
4W 
5W 
6W 
7W 
 3M 
6M 
12M 
14 days 
Informed consent 
       x 
Review of    
Histories 
       x 
Medication 
           x 
History 
+Concomitant 
Medications 
Inclusion/ 
Exclusion 
 x 
X x 
X 
x 
x 
x 
x 
x 
x 
x 
 Randomization 
X 
 Assessment 
 Questionnaire & 
 Inventories 
 GMS/GMS-I 
x 
 
 
ISI 
x                    
x 
x 
x 
x 
x 
BDI 
x 
x 
x 
x 
BAI 
x 
x  
x 
x 
x 
SRSM 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
WSL 
 
 
x 
x 
x 
x 
CGI-I 
           x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
CGI-S 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Q-LES 
x 
 
x 
 
DSM-5 diagnostic 
 Interview 
x 
C-SSRS 
           x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 

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3.0 
                         TABLE OF CONTENTS 
 
1.0 TITLE PAGE ------------------------------------------------------------------------------------------------1 
2.0 SYNOPSIS AND SCHEDUALE OF EVALUATIONS-----------------------------------------------2 
 
3.0 TANLE OF CONTENTS-----------------------------------------------------------------------------------8 
 
4.0 LIST OF ABBREVIATIONS------------------------------------------------------------------------------12 
 
5.0 ETHICAL CONSIDERATIONS--------------------------------------------------------------------------13 
5.1   INSTITUTIONAL REVIEW BOARD AND INDEPENDENT ETHICS--------------------------13 
 
5.2   COMMITTEE ETHICAL CONDUCT OF THE STUDY --------------------------------13 
 
5.3 PATIENT INFORMATION AND INFORMED CONSENT ------------------------------13 
6 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE---------------------------14 
7 
INTRODUCTION-------------------------------------------------------------------------------------------15 
 
8 
STUDY OBJECTIVES--------------------------------------------------------------------------------------22 
 
9 
INVESTIGATIONAL PLAN-------------------------------------------------------------------------------28 
9.1 OVERALL STUDY DESIGN AND PLAN: DESCRIPTION------------------------------------------28 
 
 9.1.1  IN PERSON SCREENING AND DATA GATHERING--------------------------------------------28 
 
 9.1.2 DSM-5 DIAGNOSTIC SCREENING INTERVIEW--------------------------------------------------28 
 
9.1.3 SAFTY FOLLOW UP PERIOD---------------------------------------------------------------------------31 
 
9.2 DISCUSSION OF STUDY DESIGN-----------------------------------------------------------------------34 
 
9.3 SELECTION OF STUDY POPULATION-----------------------------------------------------------------34 
 
9.3.1 INCLUSION CRITERIA ----------------------------------------------------------------------------------34 
 
9.3.2 EXCLUSION CRITERIA ----------------------------------------------------------------------------------34 
 
9.3.3 REMOVAL OF PATIENTS FROM THERAPY OR ASSESSMENT-------------------------------35 
 
9.3.4 PATIENT REPLACEMENT PROCEDURES-----------------------------------------------------------35 
 
9.4 TREATMENTS-------------------------------------------------------------------------------------------------35 
9.4.1 ASSIGNMENT TO TREATMENT & SCHEDULING-------------------------------------------------35 
9.4.2 METHOD OF ASSIGNING PATIENTS & TREATMENT GROUPS-------------------------------36 
9.4.3 CLINICAL PROCEDURES---------------------------------------------------------------------------------37 

                                                                                                                                             
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9.4.4 DATA GATHERING DURING TREATMENT---------------------------------------------------------37 
9.4.5 END OF TREATMENT-----------------------------------------------------------------------------------37 
9.4.6 SELECTION & TIMING OF 6 SESSION TREATMENT-------------------------------------------38 
9.4.6.1 SCREENING PERIOD----------------------------------------------------------------------------------38 
9.4.6.2 RANDOMIZATION OPEN-LABEL SLEEP HYGIENE CONTROLLED 6 WEEK STUDY                          
            TREATMENT PERIOD---------------------------------------------------------------------------------39 
9.4.6.3 SAFETY FOLLOW-UP PERIOD----------------------------------------------------------------------39 
9.4.7 CONCOMITANT MEDICATION -----------------------------------------------------------------------39 
9.4.7.1 PERMITTED MEDICATIONS/TREATMENTS----------------------------------------------------39 
9.4.7.2 PROHIBITED MEDICATIONS/TREATMENTS---------------------------------------------------39 
9.4.8 OTHER RESTRICTIONS---------------------------------------------------------------------------------40 
9.4.8.1 ALCOHOL-------------------------------------------------------------------------------------------------40 
9.4.9 MONITORING TREATMENT COMPLIANCE-------------------------------------------------------40 
9.4.10 TREATMENT DISCONTINUATION-----------------------------------------------------------------41 
9.5.1 DIAGNOSTIC ASSESMENTS---------------------------------------------------------------------------41 
9.5.1.2  EFFICACY ASSESMENTS----------------------------------------------------------------------------41 
9.5.1.3 THE CLINICAL GLOBAL IMPRESSIONS- SEVERITY-----------------------------------------41 
9.5.2  SAFETY ASSESSMENTS--------------------------------------------------------------------------------41 
 
9.5.2.1 ADVERSE EVENTS-------------------------------------------------------------------------------------42 
9.5.2.2 CASUALITY ASSESMENT----------------------------------------------------------------------------42 
9.5.2.3 SERVERITY ASSESMENT----------------------------------------------------------------------------42 
9.5.2.4 SERIOUS ADVERSE EVENTS------------------------------------------------------------------------43 
9.5.2.5 REPORTING ADVERSE EVENTS & SERIOUS ADVERSE EVENTS------------------------43 
9.5.2.6 COLUMBIA SUICIDE SEVERITY RATING SCALE---------------------------------------------44 
9.5.3 SCHEDULE OF ASSESMENTS-------------------------------------------------------------------------44 
9.5.3.1 VISIT 1 (SCREENING)---------------------------------------------------------------------------------45 
9.5.3.2 VISIT 2 (OR) BASELINE-------------------------------------------------------------------------------45 
9.5.3.3 VISIT 3-----------------------------------------------------------------------------------------------------45 

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9.5.3.4 VISIT 4-----------------------------------------------------------------------------------------------------46 
9.5.3.5 VISIT 5-----------------------------------------------------------------------------------------------------46 
9.5.3.6 VISIT 6-----------------------------------------------------------------------------------------------------46 
9.5.3.7 VISIT 7-----------------------------------------------------------------------------------------------------46 
9.5.3.8 VISIT 8-----------------------------------------------------------------------------------------------------46 
9.5.3.9 VISIT 9 (3 MONTHS FOLLOW-UP PERIOD)------------------------------------------------------47 
9.5.3.10 VISIT 10 (6 MONTHS FOLLOW-UP PERIOD)---------------------------------------------------47 
9.5.3.11 VISIT 11 (12 MONTHS FOLLOW-UP PERIOD)--------------------------------------------------47 
9.5.3.12 UNSCHEDULED VISIT--------------------------------------------------------------------------------48 
9.6 DATA QUALITY ASSURANCE----------------------------------------------------------------------------48 
9.6.1 DATA MONITORING---------------------------------------------------------------------------------------48 
9.6.2 DATA RECORDING AND DOCUMENTATION-------------------------------------------------------48 
9.7 STATISTICAL METHODS AND DETERMINATIONS OF SAMPLE SIZE-------------------------49 
9.7.1 SAMPLE SIZE-------------------------------------------------------------------------------------------------49 
9.7.2 ANALYSIS POPULATIONS--------------------------------------------------------------------------------49 
9.7.3 SAFETY PARAMETERS------------------------------------------------------------------------------------49 
9.7.4 COMPUTER METHODS-------------------------------------------------------------------------------------49 
9.8 DATA AND SAFETY MONITORING BOARD------------------------------------------------------------49 
9.9 CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED ANALYSES---------------------50 
9.10 PROTOCOL DEVIATIONS-----------------------------------------------------------------------------------50 
10.0 STUDY SPONSORSHIP---------------------------------------------------------------------------------------50 
10.1 STUDY TERMINATION--------------------------------------------------------------------------------------50 
10.2 REPORTING AND PUBLICATION-------------------------------------------------------------------------50 
11.0 INVESTIGATOR OBLIGATIONS---------------------------------------------------------------------------51 
11.1 DOCUMENTATION--------------------------------------------------------------------------------------------51 
11.2 PERFORMANCE------------------------------------------------------------------------------------------------51 
11.3 USE OF INVESTIGATIONAL MATERIALS--------------------------------------------------------------51 
11.4 CASE REPORT FORMS----------------------------------------------------------------------------------------52 

                                                                                                                                             
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11.5 RETENTION AND REVIEW OF RECORDS---------------------------------------------------------------52 
11.6 PATIENT CONFIDENTIALITY-------------------------------------------------------------------------------52 
12.0 INVESTIGATOR’S STATEMENT----------------------------------------------------------------------------53 
13.0 APPENDICES-----------------------------------------------------------------------------------------------------54 
APPENDIX I  ELEMENTS OF INFORMED CONSENT--------------------------------------------------------55 
APPENDIX II  CONTACT INFORMATION----------------------------------------------------------------------57 
APPENDIX III  CONCOMITANT MEDICATIONS--------------------------------------------------------------58 
APPENDIX IV  BECK’S DEPRESSION INVENTORY----------------------------------------------------------60 
APPENDIX V  BECK’S ANXIETY INVENTORY----------------------------------------------------------------64 
APPENDIX VI  GOAL MOTIVATIONAL SCALE---------------------------------------------------------------65 
APPENDIX VII  GOAL MOTIVATIONAL SCALE-INSOMNIA----------------------------------------------66 
APPENDIX VIII  INSOMNIA SEVERITY INDEX---------------------------------------------------------------67 
APPENDIX IX  SELF-REPORT SLEEP MEASURES------------------------------------------------------------68 
APPENDIX X  CLINICAL GLOBAL IMPRESSION-GLOBAL IMPROVEMENT (CGI-I) SCALE-----70 
APPENDIX XI CLINICAL GLOBAL IMPRESSIONS-SEVERITY SEVERITY OF ILLNESS-----------71 
 
APPENDIX XII  QUALITY OF LIFE ENJOYMENT AND SATISFACTION QUESTIONNAIRE-SHORT                   
FORM (Q-LES-Q-SF) ---------------------------------------------------------------------------------------------------72 
APPENDIX XIII COLUMBIA-SUICIDE SEVERITY RATING SCALE- BASELINE OR SCREENING                    
 VERSION-----------------------------------------------------------------------------------------------------------------74 
APPENDIX XIV COLUMBIA SUICIDE SEVERITY RATING SCALE- SINCE LAST VISIT------------76 
14.0 LITERATURE CITED---------------------------------------------------------------------------------------------80 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
 
4.0 
LIST OF ABBREVIATIONS 
 
BMI 
Body mass index 
BP 
Blood pressure 
CI 
Confidence interval 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition 
ET 
Early termination 
FDA 
Food and Drug Administration 
GCP 
Good clinical practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
PSPC                                 Puget Sound Psychiatry Center 
SD 
Standard deviation 
SAEs/AEs                          Serious adverse events/Adverse Events  
ANOVA                            Analysis of Variance     
PN                                     Participant Number 
eCRFs                               Electronic Case Report Forms  
MDC                                Manual Data Capture 
ECG                                 Electro Cardiogram 
BDI                                  Beck Depression Inventory  
BAI                                  Beck Anxiety Inventory  
ISI)                                   Insomnia Severity Index  
SRSM                              Self Report Sleep Measures                                          
WSL                                Weekly Sleep Log  
CGI-I                               Clinical Global Impression - Improvement  
CGI-S                              Clinical Global Impression – Severity scale  
Q-LES                             Quality of Life Enjoyment and Satisfaction   
EOT/ET                           End of Treatment/Early Termination  
C-SSRS                           Columbia suicide severity rating scale  
BV                                   Baseline Visit  
CBT                                 Cognitive behavioral therapy 
CBT-I                              Cognitive Behavior Therapy for Insomnia  
FOA                                Focus of Attention  
SAS                             Software; Statistical Analysis System 
DSMB                            Data and Safety Monitoring Board  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                             
1 
 
 
5.0 
                        ETHICAL CONSIDERATIONS 
5.1 
INSTITUTIONAL REVIEW BOARD AND INDEPENDENT 
ETHICS COMMITTEE 
 
 
Approval by the local IRB/PSPC Ethical Committee, before the start of the study will be the 
responsibility of the Investigator. A copy of the approval letter will be supplied to the Sponsor-PSPC, 
along with a roster of IRB members. During the course of the study, the Investigator will provide timely 
and accurate reports to the IRB on the progress of the study, at intervals not exceeding 1 year (or as 
appropriate), and will notify the IRB of serious adverse events (SAEs) or other significant safety 
findings. The study protocol, informed consent form (ICF), information sheet advertisements, and 
amendments (if any) will be approved by the IRBs at the study centers in conformance with the US CFR, 
Title21, Part 56. 
 
5.2 
ETHICAL CONDUCT OF THE STUDY 
 
This clinical study will be conducted in accordance with the ethical principles that have their origins in 
the Declaration of Helsinki. This clinical study will comply with the ICH Guidance on General 
Considerations for Clinical Trials (ICH-E8; 62 FR 66113, 17 Dec 1997) and GCP (ICH-E6; 62 FR 
25692, 09 May 1997).  
 
5.3 
PATIENT INFORMATION AND INFORMED CONSENT 
 
After being given an explanation of the study and before participating in any study procedures, each 
patient must provide written informed consent in compliance with 21 CFR, Parts 50 and give HIPAA 
authorization. 
 
Each patient will read and sign an ICF and/or other authorization form as per local regulations; each 
patient will be made aware that he or she may withdraw from the study at any time. 
 
The ICF contains all the elements of informed consent listed in Appendix I of this protocol. Signed 
copies of the ICF and the HIPAA or other locally applicable form will be given to the patient, and both 
documents will be placed in the Investigator‘s study files. 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
 
6.0                INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
 
 
This study will be performed at Puget Sound Psychiatry Center (PSPC) Bothell WA,  in the United States.  
The Investigator is responsible for ensuring that the investigation is conducted according to the signed 
Investigator statement, the investigational plan, GCP guidelines, and applicable regulations; for protecting 
the rights, safety, and welfare of patients under the Investigator‘s care; and for the control of investigational 
products under investigation. An investigator shall obtain the informed consent for each patient prior to the 
patient enrolling in the study and/or prior to participating in any study-related activity. 
 
The Investigator at Puget Sound Psychiatry Center (PSPC) must meet his or her obligations to the 
patients, ethics committee, Sponsor, and regulatory authorities by maintaining oversight and control of 
the study‘s conduct and the study staff. It is the responsibility of the Investigator to ensure that any and 
all delegated duties be assigned to qualified staff by education, experience, and licensure (in accordance 
with local regulations) and that the Investigator oversight is documented and assessment of staff 
capabilities and performance is consistent with the study investigational plan. The Investigator at Puget 
Sound Psychiatry Center (PSPC) will be responsible for the management of the study, including 
maintaining the study file and the patient records, corresponding with the IRB, and completing the 
electronic case report forms (eCRFs). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                             
1 
 
 
7.0                                                           INTRODUCTION 
 
REVIEW OF RELATED LITERATURE: BEHAVIORAL TREATMENT OF 
INSOMNIA DISORDER 
 
The annual prevalence of insomnia symptoms in the general adult population ranges from 35% to 50% 
(Walsh, Coulouvrat & Hajak et al, 2011).  To distinguish chronic from acute insomnia, which may occur 
in anyone at one time or another, varied definitions for chronic insomnia have been utilized from study to 
study, with minimum durations ranging from 30 days to as long as 6 months (National Institutes of Health, 
2005).  The prevalence of insomnia disorder ranges from 12% to 20% (Morin, LeBlanc, Belanger, Ivers, 
Merette, & Savard J. 2011; Roth, Coulouvrat, & Hajak et al. 2011). 
Insomnia Disorder involves a predominant complaint of dissatisfaction with sleep quantity or quality, 
associated with one or more of the following symptoms: (1) difficulty initiating sleep, (2) difficulty 
maintaining sleep characterized by frequent awakenings or problems returning to sleep after awakenings; 
(3) early morning awakening with inability to return to sleep (American Psychiatric Association, 2013).  
Sedative hypnotics or antidepressant drugs are the most common treatments offered patients who meet 
clinical criteria for Insomnia Disorder (Walsh & Schweitzer, 1999).  Numerous negative side effects 
accompany traditional hypnotics, e.g., benzodiazepines.  In addition, these drugs provide only symptomatic 
relief because they do not address underlying mechanisms which sustain primary insomnia.  As a result, 
upon termination of the sleep medications, patients very commonly experience a full return of their 
insomnia symptoms. Given the prevalence of insomnia and the limited effectiveness of medication for the 
treatment of insomnia disorder, there is a need for non-pharmaceutical behavioral treatment approaches. 
 
COGNITIVE BEHAVIORAL THERAPY FOR INSOMNIA: 
Cognitive behavioral therapy for insomnia (CBT-I) is the most prominent non-pharmacologic treatment for 
insomnia disorder (Wu, Appleman, Salazar & Ong, 2015).  Early in the development of what is now “CBT-
I”, first generation behavioral interventions were designed to target presumed perpetuating mechanisms 
involved in primary insomnia.  The approach aimed to correct sleep disrupting habits using stimulus control 
and to reduce bedtime arousal using relaxation training, for example.  Over time cognitive behavior therapy 
for insomnia has adopted a multi-component approach to treatment.   
As noted by Perlis et al (2008), the clinical practices which constitute the primary or first line components 
are to some extent debated.  However, most clinical practices and clinical trial protocols now include (1) 
stimulus control therapy and (2) sleep restriction therapy along with (3) sleep hygiene education, (4) 
cognitive therapy to identify and reduce negative sleep thoughts, and often (5) relaxation strategies such as 
progressive muscle relaxation and bedtime rituals that facilitate calming, especially as bedtime approaches.  
(1) Stimulus control is a set of instructions originally developed by Richard Bootzin that address 
conditioned arousal.  These instructions strengthen the bed and bedroom as a cue for sleep and weaken the 
bed and bedroom as a cue for wakefulness.  (2) Sleep restriction therapy or “sleep consolidation training” 
is a procedure originally designed by Arthur Spielman to eliminate prolonged awakenings in the middle of 
the night.  The procedure can also help with difficulty initiating asleep at the beginning of the night.  This 
step-wise procedure aims to first improve sleep quality and later worry about sleep quantity. The time spent 
in bed is initially restricted to the currently feasible amount of sleep.  Time spent in bed is gradually 
increased in subsequent steps.  (3) Sleep hygiene education commonly lists best practices in sleep hygiene 
(get up at the same time each day, cut down on all caffeine products, make sure your bedroom is at a 
comfortable temperature during the night, etc.).  Typically this involves education, then identifying specific 
sleep hygiene practices for improvement, identifying goals and follow up.  (4) Cognitive therapy and (5) 
relaxation therapy are often included on an as needed basis to bolster incomplete treatment responses and 
address predisposing and precipitating factors thought to still be substantially contributory (Perlis et al, p. 

2 
17).  The cognitive therapy component identifies negative sleep talk such as “I can’t stand it that I’m not 
getting to sleep” or “If I don’t get 8 hours of sleep tonight, I’ll do poorly at work and I could get fired”.  
Some cognitive therapists have a didactic focus.  Others use a variety of cognitive restructuring procedures.  
While the therapies differ in approach, all are based on the observation that persons with insomnia have 
negative thoughts and beliefs about their condition and its consequences (Perlis, p. 18).  Relaxation therapy 
focuses on managing stress, muscle relaxation and bedtime rituals that facilitate calming [https:// 
stanfordhealthcare.org/medical-treatments/c/cognitive-behavioral-therapy-insomnia.html]. 
 
EFFECTIVENESS OF CBT-I: 
The results using CBT-I among subjects with primary insomnia reporting sleep onset problems have been 
moderately effective for treating sleep onset problems.  In a meta-analysis of 37 studies, Wu, Appleman, 
Salazar and Ong (2015) reported 36% of CBT-I patients were in remission from insomnia and no longer 
met diagnostic criteria for Insomnia Disorder at post-treatment evaluation compared to 16.9% in 
comparison conditions.   
Key quantitative measures include sleep latency, the amount of time it takes person to initiate sleep upon 
retiring to bed; wake time after sleep onset (WASO); total sleep time (TST); and sleep efficiency, the 
percentage of sleep period during which person is actually asleep. In their review of the results of five 
randomized clinical trials which compared CBT-I to medications among patients with primary insomnia, 
Mitchell, Gehman, Perlis and Umscheid (2012) report sleep efficiency improved 8 to 16 percent with CBT-
I.  CBT-I generally led to improvement of 30 to 45 minutes in sleep latency and 30 to 60 minutes in total 
sleep time.  Note that TST is not only an outcome variable but is manipulated as part of CBT-I using the 
restriction of time spent in bed.  Sleep restriction therapy requires that time in bed be reduced to a time 
interval equal to the patient’s ‘sleep ability’ by measuring average TST with a sleep log during a baseline 
period. As noted by Mitchell, Gehrman, Perlis and Umscheid, “The net result of this, after completion of 
CBT-I, is that many patients do not recover their baseline TST but are nevertheless substantially improved 
with respect to other aspects of sleep” (p. 6).  
 
LIMITATIONS OF COGNITIVE BEHAVIOR THERAPY FOR INSOMNIA: 
According to Mitchell et al “There are two main disadvantages to CBT-I.  First, during the first few week 
of treatment there is often an acute reduction in total sleep time that can lead to the side effect of increased 
daytime sleepiness which, for some, is enough to lead them to drop out of treatment.  Second, improvements 
from CBT-I are typically not seen until 3-4 weeks into treatment” (p. 3 of 18).  Also noteworthy is the 
emotional response of patients upon learning their sleep will be restricted, commonly with a markedly later 
bedtime during the implementation of sleep restriction.  Although apparently no research to date has 
assessed patient satisfaction and/or distress during treatment implementation, this may be a factor related 
to dropout rate with CBT-I.  Among ten randomized controlled trials of CBT-I for primary insomnia 
reporting dropout rate and involving sleep restriction, dropout rates ranged from 0% to 33%.  Specifically, 
4 studies reported 0% dropout; 1 study reported 7% dropout; 2 studies reported 8% dropout; and dropout 
rates of 11%, 18% and 33% were each reported in one study (Table 1, Okajima, Komada & Inque, 2011). 
In addition, while 36% remission of insomnia disorder is better than 16.9% (comparison group), this means 
64% of those completing CBT-I continued to meet diagnostic criteria for Insomnia Disorder (Wu, 
Appleman, Salazar and Ong, 2015).  With all due respect for the major contribution of CBT-I in assisting 
those with insomnia, there is room for improvement as evidenced by 64% still having Insomnia Disorder 
upon completion of treatment.  
Another potential limitation of CBT-I relates to the mechanism of change and may lead to a means to 
improve upon the efficacy of behavioral treatment(s) for insomnia.  “Research by Gregg D. Jacobs, Ph.D. 
and colleagues has established that insomniacs have faster brain wave patterns in bed than good sleepers 
which is consonant with heightened mental activity.” (Jacobs, 2000, p. 22).  The faster brain wave pattern 
is only partially addressed in CBT-I which focuses on negative sleep talk. However, the emphasis in CBT-
I is upon reality testing and/or challenging negative sleep talk, not upon slowing the faster brain wave 
pattern itself.  A behavioral treatment approach which targets the actual here-and-now brain wave frequency 

                                                                                                                                             
1 
with the goal of slowing the brain wave frequency in the moment at the time when the person wants to go 
to sleep may further improve their ability to do so.  
 
BRAIN WAVE FREQUENCY AND SLEEP: 
The human brain is composed of neurons that are interconnected to each other in networks.  These neurons 
receive inputs from other areas of the brain.  Electrical activity in the form of nerve impulses is always 
present in the form of nerve impulses being sent and received, even during sleep.  The electrical activity 
reflects both intrinsic activity of neurons in the cerebral cortex (an internal process, i.e., thinking) and 
information sent to it by the body and sensory receptors (input from sight, sound, smell, touch).  This 
composite activity is measured with an electroencephalogram or EEG.  An EEG mainly detects the activity 
of the brain region just under it, the cerebral cortex.  Nevertheless, the electrodes receive the activity from 
thousands of neurons.  In fact, one square millimeter of cortex has more than 100,000 neurons.   
 
Frequency 
range 
Name 
Usually associated with: 
13–39 Hz 
Beta 
waves 
Active, busy or anxious thinking and active concentration, arousal, 
cognition, and or paranoia 
7–13 Hz 
Alpha 
waves 
Relaxation (while awake), pre-sleep and pre-wake drowsiness, REM 
sleep, Dreams 
4–7 Hz 
Theta 
waves 
Deep meditation/relaxation, NREM sleep 
< 4 Hz 
Delta 
waves 
Deep dreamless sleep, loss of body awareness 
 
(Precise boundaries between ranges vary among definitions; there is no universally accepted standard). The 
dominant frequency determines one's current state. For example, if alpha waves are dominating, the person 
is in the alpha state.  This happens when one is relaxed but awake.  However, other frequencies will also 
be present, although with smaller amplitudes. Falling asleep for a waking state begins with Stage 1 (non-
REM) which is the stage between wakefulness and sleep, sometimes referred to as somnolence or drowsy 
sleep, in which the muscles are still quite active and the eyes roll around slowly and may open and close 
from time to time.  In more scientific terms, stage 1 is the period of transition from relatively 
unsynchronized beta and gamma brain waves (with a frequency of 12-30 Hz and 25-100 Hz respectively), 
which is the normal range for the awake state, to more synchronized but slower alpha waves with a 
frequency of 8-13 Hz, and then to theta waves with a frequency of 4-7 Hz.  It is difficult to pinpoint the 
actual point of sleep onset (falling asleep), as the process is a continuum as brain wave activity gradually 
slows down (http://www.howsleepworks.com/types_nonrem.html). 
In short, a predominant lower brain wave frequency is associated with sleep, and a predominant higher 
brain wave frequency is associated with busy or anxious thinking and arousal.  Therefore shifting the 
predominant brain wave frequency to a lower frequency should be associated with increased ability to 
initiate sleep. How can lower brain wave frequencies be increased when a person wants to sleep?  A 
potential answer to this question and an associated treatment approach for insomnia comes primarily from 
the literature on meditation with ancillary guidance from the literature on brain entrainment. 
MEDITATION: 
Meditation’s effect on the brain can be put into two categories: state changes and trait changes, respectively 
alterations in brain activities during the act of meditating and changes that are the outcome of long-term 

2 
practice.  The former is of interest as relates to lowering the predominant brain wave frequency to increase 
ability to initiate sleep.  Assessed in a review by Cahn and Polich (2006), many studies on meditation have 
linked frequency alpha (8-13 Hz) and theta (4-7 Hz) waves to meditation (Cahn & Polich, 2006).  A much 
older study reports more specific findings, such as decreased alpha blocking and increased frontal lobe 
specific theta activity.  Alpha blocking is a phenomenon where the active brain, normally presenting beta 
wave activity, cannot as easily switch to alpha wave activity (Kasamatsu & Hirai, 1966). 
Envision a person is in bed, head on the pillow, sheet and blanket covering them, eyes closed, and wanting 
to go to sleep.  If the person does not go to sleep, they are very likely thinking about things.  For example, 
they might think about what a family member said or something they have to do tomorrow.  In any event, 
thinking about things activates the brain, and the brain activation maintains a higher predominant brain 
wave frequency which is associated with being awake.  In essence, that upon which the person focuses their 
attention stimulates a certain brain wave frequency.  Imagine falling out a window several stories above 
street level, for example, and notice how anxiety immediately increases.  Think of the possibility a loved 
one’s flight tomorrow will crash, and anxiety level will again immediately increase.  These examples 
illustrate how focus of attention relates to brain wave frequency: anxiety reflects a higher predominant brain 
wave frequency at the moment.  In short, a person’s focus of attention relates to their predominant brain 
wave frequency.   
When in bed and wanting to initiate sleep, “thinking about things” reflects the mind focused on activating 
thoughts.  These activating thoughts relate to higher brain wave frequency.  Thus the person has difficulty 
initiating sleep, a phenomenon associated with a lower brain wave frequency.  With the focus on something 
less activating, it is reasonable to believe the predominant brain wave frequency will be lower. Meditation 
eliminates background mental noise, commonly by focusing attention on the breathe (yoga, for example), 
a mantra (transcendental meditation), a calming image (guided imagery), or non-judgmental observation of 
one’s own thinking (mindfulness).  As relates to facilitating sleep, the sound of the breath and a mantra are 
of particular interest as steady, unmoving auditory processes.  Imagery involves the visual brain, and it is 
the auditory brain which is activated while “thinking about things”.  Mindfulness meditation focuses on 
observing one’s own thinking process, which is itself an ever shifting phenomenon and therefore at least 
mildly activating.  While in bed trying to sleep, the act of thinking “Oh, I have to remember to pay the rent 
tomorrow” involves auditory activation.  A much less activating auditory stimulus is the sound of one’s 
breathing. Shifting and then maintaining the focus of attention on listening to the sound of here-and-now 
breathing shifts the auditory brain to a less activating auditory stimulus, thereby lowering the predominant 
brain wave frequency.  One tends to become bored with continued listening to the sound of one’s own 
breath.  Boredom reflects less activation.  Similarly, repeating a non-stimulating mantra again and again in 
one’s mind shifts the focus to a less activating auditory stimulus, thereby lowering the predominant brain 
wave frequency. 
Lower brain wave frequency is associated with relaxation, deep meditation and sleep.  Therefore, meditative 
practices which increase the predominance of lower brain waves appear fitting as a means of increasing the 
ability to initiate sleep. The first author has been using specific meditative strategies with outpatient clients 
whose therapy goals include increased ability to initiate sleep.  The meditation strategies are (1) listening 
to the sound of one’s own breathing; (2) using a mantra to slow and quell thinking; and (3) guided imagery 
linking breathing with focus on calming during exhalation.  With an explanation of the approaches and 
specific directions for focusing attention on listening to the sound of their own breathing, clients whose 
overall anxiety level is low to moderate often report the next week, “It works.”  However, clients whose 
overall anxiety level is moderate to high often report the next week, “It works a little.” “Some nights it 
worked.  Some nights I just couldn’t stop thinking about things.”  As follow up, when these more anxious 
clients are then given an explanation and specific directions for using a mantra, these clients often report 
the next week, “It works.”  As follow up with more anxious clients reporting considerable body activation, 
specific directions are given for guided imagery to link the calming body sensation with breathing out. 
Listening in the moment to the sound of the breath is a more passive activity, presumably with less brain 
activation than actively repeating a mantra.  If in fact manta-based meditation is more effective in slowing 
the brain of the more anxious person, brain entrainment provides one possible explanation.  Here is a 

                                                                                                                                             
1 
synopsis on brain entrainment, followed by a working hypothesis regarding the differential effectiveness 
of the two meditative strategies. 
 
BRAIN ENTRAINMENT: 
Human subjects rarely hear frequencies below 20 Hz, which is exactly the range of Delta, Theta, Alpha, , 
and low to mid Beta brainwaves.  Among the methods by which some investigations have sought to induce 
lower brain wave frequencies is to have subjects listen to binaural beats.  A binaural beat is an auditory 
illusion perceived when two different pure-tone sine waves, both with frequencies lower than 1500 Hz, 
with less than a 40 Hz difference between them, are presented to a listener, one through each ear.  For 
example, if a 530 Hz pure tone is presented to a subject's right ear, while a 520 Hz pure tone is presented 
to the subject's left ear, the listener will perceive the auditory illusion of a third tone, in addition to the two 
pure-tones presented to each ear. The third sound is called a binaural beat, and in this example would have 
a perceived pitch correlating to a frequency of 10 Hz, that being the difference between the 530 Hz and 
520 Hz pure tones presented to each ear (Draganova, Ross, Wollbrink & Pantev, 2008).  
Listening to binaural beats has been shown to precipitate auditory driving by which ensembles of cortical 
neurons entrain their frequencies to that of the binaural beat, with associated changes in self-reported 
subjective experience of emotional and cognitive state (Becher, Höhne, Axmacher, Chaieb, Elger & Fell, 
2015; Pratt, Starr, Michalewski, Dimitrijevic, Bleich & Mittelman, 2009; Karino, Yumoto, Itoh, Uno, 
Yamakawa, Sekimoto & Kaga, 2006; McConnell, Froeliger, Garland, Ives & Sforzo, 2014).  The brain 
entraining is more effective if the entraining frequency is close to the user's starting dominant frequency.  
Therefore, it is suggested to start with a frequency near to one's current dominant frequency (likely to be 
about 20 Hz or less for a waking person) and then slowly decrease or increase it towards the desired 
frequency.  
 
IMPLICATIONS FOR MEDITATION PRACTICES FOR INSOMNIA: 
While brain entrainment provides a means of stimulating a particular brain wave frequency, the approach 
requires expensive equipment not commonly available and to date untested in the treatment of insomnia.  
It nonetheless provides guidance in the process of shifting the brain wave frequency.  Specifically, a strategy 
that increases the frequency slightly lower than the predominant brain wave frequency at hour of sleep may 
be more effective than a strategy that increases a frequency markedly lower than the predominant frequency 
at that moment. 
 
SUMMARY: 
The prevalence of insomnia disorder ranges from 12% to 20%.  The most prominent non-pharmacologic 
treatment for insomnia disorder is cognitive behavioral therapy for insomnia (CBT-I).  Meta-analysis 
indicates 36% remission of insomnia disorder upon completion of CBT-I vs. 16.9% in the comparison 
group(s). This means 64% of those completing CBT-I continued to meet diagnostic criteria for Insomnia 
Disorder.  While CB-I has made a major contribution in assisting those with insomnia, there is room for 
improvement as evidenced by 64% still having Insomnia Disorder upon completion of treatment with CBT-
I.  
Research has established that insomniacs have faster brain wave patterns in bed than good sleepers which 
is consonant with heightened mental activity. The mechanisms of action for CBT-I do not directly address 
the faster brain wave patterns.  Assessed in a review by Cahn and Polich (2006), many studies on meditation 
have linked frequency alpha (8-13 Hz) and theta (4-7 Hz) waves to meditation (Cahn & Polich, 2006).  A 
predominance of these lower brain wave frequencies has been found to be directly related to relaxation and 
sleep.  The first author’s clinical use of meditation techniques to increase clients’ ability to initiate sleep 
has met with frequent client feedback that “It works”.  This approach, called “focus of attention” appears 
promising.  However, “It works” is not sufficient.  A clinical trial is needed in order to assess the relative 
efficacy of (a) cognitive behavior therapy for insomnia, (b) focus of attention [FOA], (c) a combination of 
CBT-I and FOA and (d) a comparison group.  

2 
 
 
REFERENCES: 
American Psychiatric Association.  Diagnostic and Statistical Manual of Mental Disorders, 5th 
edition.  Washington, DC: American Psychiatric Association, 2013. 
Becher AK, Höhne M, Axmacher N, Chaieb L, Elger CE & Fell J. Intracranial electroencephalography 
power and phase synchronization changes during monaural and binaural beat stimulation. European Journal 
of Neuroscience, Vol. 41, No. 2, 2015, pp. 254-263. doi:10.1111/ejn.12760. PMID 25345689 
 
Cahn, BR & Polich, J. (2006).  “Meditation states and traits: EEG, ERP, and neuroimaging studies”.  
Psychological Bulletin, 132 (2): 180-211.  Doi: 10.1037/0033-2909.132.2180. PMID 16536641. 
Draganova R, Ross B, Wollbrink A & Pantev C. (2008). Cortical steady-state responses to central and 
peripheral auditory beats. Cerebral Cortex Vol. 18, 2008, pp1193–1200. 
 
Jacobs, GD.  Clinical Training Manual for a CBT-I Insomnia Program.  Copyright 2000-2010 Gregg D. 
Jacobs.   
 
Mitchell MD, Gehrman P, Perlis M, & Umscheid CA.  Comparative effectiveness of cognitive behavioral 
therapy for insomnia: A systematic review.  BMC Fam Pract. 2012; 13: 40. [Published on line 2012 May 
25. Doi: 10.1186/1471-2296-13-40.] 
 
Karino S, Yumoto M, Itoh K, Uno A, Yamakawa K, Sekimoto S & Kaga K. (2006). Neuromagnetic 
responses to binaural beat in human cerebral cortex. Journal of Neurophysiology, Vol. 96, No. 4, 2006, 
pp1927-1938. 
 
Kasamatsu KH & Hirai T (1966). “An electroencephalographic study on the zen meditation (Zazen)”.  
Psychiatrica et Neurologica Japonica, 20 (40: 315-336. Doi:10/1111k/1440-1819.1966.tb02646.x. 
 
McConnell PA, Froeliger B, Garland EL, Ives JC & Sforzo, GA.  Auditory driving of the autonomic nervous 
system: Listening to theta-frequency binaural beats post-exercise increases parasympathetic activation and 
sympathetic withdrawal. Frontiers in Psychology, Vol. 5, 2014 
 
Morin CM, LeBlanc M, Belanger L, Ivers H, Merette C & Savard J.  Prevalence of insomnia and its 
treatment in Canada. Canadian Journal of Psychiatry, 2011; 56(9): 540-548.  
 
Okajima I,  Komada Y & Inque, Y.  A meta-analysis on the treatment effectiveness of cognitive behavioral 
therapy for primary insomnia.  Sleep and Biological Rhythms, 2011; 9: 24-34. 
 
Perlis ML, Jungquist C, Smith MT & Posner, D.  Cognitive Behavioral Treatment of Insomnia: A Session-
by-Session Guide. 2008. New York: Springer. 
Pratt, H, Starr A, Michalewski HJ, Dimitrijevic A, Bleich N & Mittelman N. Cortical evoked potentials to 
an auditory illusion: binaural beats. Clinical Neurophysiology, Vol. 120, No. 8, 2009, pp1514-1524. 
 
Roth T, Coulouvrat C, Hajak G et al.  Prevalence and perceived health associated with insomnia based 
on DSM-IV-R-TR; International Statistical Classification of Diseases and Related Health Problems, Tenth 

                                                                                                                                             
1 
Revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders, Second 
Edition criteria: results from the America Insomnia Survey.  Biological Psychiatry. 2011; 69(6): 592-600. 
 
National Institutes of Health State of the Science Conference Statement: Manifestations and Management 
of Chronic Insomnia in Adults. June 13-15, 2005. Sleep, 28(9): 1049-1057. 
  
Walsh JK, Coulouvrat C, Hajak G et al. Nighttime insomnia symptoms and perceived health in the America 
Insomnia Survey (AIS).  Sleep, 2011; 34(8): 99; 7-1011].   
Walsh JK & Schweitzer PK.  Ten-year trends in the pharmacologic treatment of insomnia. Sleep. 1999; 
22:371-375. 
 
Wu JQ, Appleman ER, Salazar RD & Ong JC.  Cognitive behavioral therapy for insomnia comorbid 
with psychiatric and medical conditions: A meta-analysis.  JAMA Intern Med. 2015; 175(9): 1461-
1472. [Published online before print July 6, 2015]. doi: 10: 1001/jamainternmed.2015.3006]. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
8.0 
                            STUDY OBJECTIVES 
 
The objectives of this study seeks to evaluate and compare the effectiveness of (1) cognitive behavior 
therapy for insomnia [CBT-I], (2) focus of attention [FOA], (3) a combination of cognitive behavior 
therapy for insomnia and focus of attention,  and (4) a sleep hygiene control intervention.   
 
PRIMARY OBJECTIVE The primary objective is completion of 6 treatment sessions and completion 
of the 3 months, 6 months and 12 months follow-up assessment. Improvement of insomnia outcome is 
measured by Self Report Sleep Measures (SRSM). 
 
SECONDRY OBJECTIVE The Secondary objective is improvement outcomes. 
 
SAFETY AND TOLERABILITY END POINTS 
In general the potential risks for participants are minimal.  The treatment approaches involved in related 
studies have been shown to be a safe procedure and in most of the published studies people who 
underwent these procedures did not report any harmful effects.  It is nonetheless possible participant(s) 
may experience some discomforts during the treatment.  These may include temporary decrease in time 
asleep and accompanying daytime drowsiness.  Some people may become anxious while initially 
following the treatment procedures, with increased worry about their sleep difficulty.  Anxiety and worry 
about sleep difficulty are in fact common among persons with insomnia.  Therefore identifying and 
addressing these possibilities will be directly addressed during the treatment, and participants will be 
given guidance about what to expect and how to manage should these discomforts occur. Persons with 
certain medical illnesses, certain psychiatric illnesses or other sleep disorders may be at increased 
potential risk of exacerbation of that illness.  This is a possibility for participants with epilepsy, bipolar 
depression, parasomnia, obstructive sleep apnea or other illnesses which have excessive daytime 
sleepiness as a feature of the parent disorder.  The participant may (or may not) be assigned to a treatment 
which involves sleep restriction.  Sleep loss through sleep restriction may 
 
1) Lower the threshold for seizures in persons with epilepsy; 
2) Precipitate mania in bipolar participants; 
3) Exacerbate parasomnias; 
4) Prevent adequate ventilation in patients with obstructive sleep apnea; and/or 
5) Aggravate the day time somnolence to the point where it is no longer safe for the participant to 
drive, operate machinery and/or make judgments that adequately promote their own and/or the 
safety and well-being of others. 
The risk is generally higher when these illnesses are untreated.  Prospective participants treated for any of 
these illnesses and interested in participating must have the written approval of their treatment provider in 
order to be eligible. Prospective participants will be screened and informed of these potential risks.  
If any of these risks (1-5 above) occur during the study, the participant will be asked to immediately 
discontinue the sleep restriction, and an alternative treatment not involving sleep restriction will be 
offered.  The participant will also have the option of discontinuing the treatment if they prefer this to 
proceeding with the alternative treatment which does not involve sleep restriction. 
 
SAMPLE SIZE 
It is estimated that 320 prospects will need to be screened in order to have 40 per group for a total of 160 
participants. 
 
 
 
 
 

                                                                                                                                             
1 
ANALYSIS POPULATIONS 
Safety Population: will include all randomized subjects who meet eligibility criteria and meet with their 
treatment provider for session 1. 
Intent-to-Treat Population: will include all subjects who meet with their treatment provider for session 1 
and for whom the treatment provider determines the subject meets diagnostic criteria for 780.52 Insomnia 
Disorder. 
Pre-Protocol (PP) Population: will include all subjects who complete the 6 sessions of treatment as well 
as the 3 month, 6 month and 12 month follow up assessment.  It is estimated that 80% of those who 
complete session 1 will complete session 6.  It is estimated that 80% of those who complete session 6 will 
complete the 3 month, 6 month and 12 month follow up assessments.  This will result in 25 participants 
who will have completed the entire study. 
 
HYPOTHESES 
Hypothesis 1: Treatment Effect on Subjective Measures from Weekly Sleep Log 
There will be no statistically significant overall post-treatment minus pre-treatment differences across the 
four treatment groups in subjective sleep measures using standardized sum scores across the four 
measures of self-report data from Weekly Sleep Log. If ANOVA indicates a significant overall 
difference, pairwise t-tests will test the following hypotheses: 
Hypothesis 1a. There will be no statistically significant post-treatment minus pre-treatment mean 
differences across the four treatment groups in the mean number of minutes to initiate sleep (SL); 
Hypothesis 1b. There will be no statistically significant post-treatment minus pre-treatment differences 
across the four treatment groups in the mean number of minutes to return to sleep upon awakening after 
sleep onset (WASO); 
Hypothesis 1c. There will be no statistically significant post-treatment differences across the four 
treatment groups in the mean total number of minutes of sleep (TST); 
Hypothesis 1d. There will be no statistically significant post-treatment minus pre-treatment differences 
across the four treatment groups in the mean total number of minutes of sleep divided by the total number 
of minutes in bed (SE). 
 
Hypothesis 2: Treatment Effect on Objective Measures of Sleep 
There will be no statistically significant overall post-treatment minus pre-treatment differences across the 
four treatment groups in overall objective sleep measures using standardized sum scores for data from 
subjects wearing an ActiWatch 2.  If ANOVA indicates a significant overall difference, pairwise t-tests 
will test the following hypotheses: 
Hypothesis 2a. There will be no statistically significant post-treatment minus pre-treatment mean 
differences across the four treatment groups in the mean number of minutes to initiate sleep (SL); 
Hypothesis 2b. There will be no statistically significant post-treatment minus pre-treatment differences 
across the four treatment groups in the mean number of minutes to return to sleep upon awakening after 
sleep onset (WASO); 
Hypothesis 2c. There will be no statistically significant post-treatment minus pre-treatment differences 
across the four treatment groups in the mean total number of minutes of sleep (TST); 
Hypothesis 2d. There will be no statistically significant post-treatment minus pre-treatment differences 
across the four treatment groups in the mean total number of minutes of sleep divided by the total number 
of minutes in bed (SE). 
 
Hypothesis 3: Treatment Effect on Insomnia Severity 
There will be no statistically significant post-treatment minus pre-treatment mean differences across the 
four treatment groups in insomnia severity as measured by the Insomnia Severity Index (ISI). 
 
 
 

2 
Hypothesis 4: Treatment Effect on Insomnia Diagnosis 
There will be no statistically significant (chi square) post-treatment minus pre-treatment mean differences 
across the four treatment groups in the percentage of subjects who meet DSM-5 criteria for 780.52 
 Insomnia Disorder across time (pre-treatment; post-treatment). 
 
Hypothesis 5: Treatment Effect on Self Report Sleep Satisfaction Measures 
There will be no statistically significant overall post-treatment minus pre-treatment differences across the 
four treatment groups in overall satisfaction/dissatisfaction with sleep using standardized sum scores for 
data from subjects across the five likert scale measures of satisfaction/dissatisfaction on the Self Report 
Sleep Measures.   
If ANOVA indicates a significant overall difference, pairwise t-tests will test the following hypotheses: 
Hypothesis 5a. There will be no statistically significant post-treatment minus pre-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
ability to get to sleep at bedtime; 
Hypothesis 5b. There will be no statistically significant post-treatment minus pre-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
frequency of awakenings after having initiated sleep; 
Hypothesis 5c. There will be no statistically significant post-treatment minus pre-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
ability to return to sleep after awakenings during the night; 
Hypothesis 5d. There will be no statistically significant post-treatment minus pre-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
average quantity of sleep; 
Hypothesis 5e. There will be no statistically significant post-treatment minus pre-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
overall quality of sleep. 
 
Hypothesis 6: Treatment Effect on Subjective Sleep Distress 
There will be no statistically significant post-treatment minus pre-treatment mean differences across the 
four treatment groups in self report of extent of distress with sleep difficulty.   
 
Hypothesis 7: Treatment Effect on Subjective Report of Impairment 
There will be no statistically significant overall post-treatment minus pre-treatment differences across the 
four treatment groups in overall self-report of impairment due to sleep difficulty measures using 
standardized sum scores across the three measures.  If ANOVA indicates a significant overall difference, 
pairwise t-tests will test the following hypotheses: 
Hypothesis 7a. There will be no statistically significant post-treatment minus pre-treatment mean 
differences across the four treatment groups in self report of extent of social impairment due to sleep 
difficulty; 
Hypothesis 7b. There will be no statistically significant post-treatment minus pre-treatment mean 
differences across the four treatment groups in self report of extent of occupational impairment due to 
sleep difficulty; 
Hypothesis 7c. There will be no statistically significant post-treatment minus pre-treatment mean 
differences across the four treatment groups in self report of extent of academic impairment due to sleep 
difficulty. 
 
Hypothesis 8: Endurance of Treatment Effect on Subjective Measures from Weekly Sleep Log 
There will be no statistically significant overall 12 month follow up minus pre-treatment differences 
across the four treatment groups in subjective sleep measures using standardized sum scores across the 
four measures of self-report data from Weekly Sleep Log. If ANOVA indicates a significant overall 
difference, pairwise t-tests will test the following hypotheses: 

                                                                                                                                             
1 
Hypothesis 8a. There will be no statistically significant 12 month follow up minus pre-treatment mean 
differences across the four treatment groups in the mean number of minutes to initiate sleep (SL); 
Hypothesis 8b. There will be no statistically significant 12 month follow up minus pre-treatment 
differences across the four treatment groups in the mean number of minutes to return to sleep upon 
awakening after sleep onset (WASO); 
Hypothesis 8c. There will be no statistically significant 12 month follow up minus pre-treatment 
differences across the four treatment groups in the mean total number of minutes of sleep (TST); 
Hypothesis 8d. There will be no statistically significant 12 month follow up minus pre-treatment 
differences across the four treatment groups in the mean total number of minutes of sleep divided by the 
total number of minutes in bed (SE). 
 
Hypothesis 9: Endurance of Treatment Effect on Objective Measures 
There will be no statistically significant overall significant overall 12 month follow up minus pre-
treatment differences across the four treatment groups in overall objective sleep measures using 
standardized sum scores for data from subjects wearing an ActiWatch 2.   
If ANOVA indicates a significant overall difference, pairwise t-tests will test the following hypotheses: 
Hypothesis 9a. There will be no statistically significant post-treatment minus pre-treatment differences 
across the four treatment groups in each of the following objective sleep measures using data from 
subjects wearing an ActiWatch 2: 
Hypothesis 9b. There will be no statistically significant 12 month follow up minus pre-treatment mean 
differences across the four treatment groups in the mean number of minutes to initiate sleep (SL); 
Hypothesis 9c. There will be no statistically significant 12 month follow up minus pre-treatment 
differences across the four treatment groups in the mean number of minutes to return to sleep upon 
awakening after sleep onset (WASO); 
Hypothesis 9d. There will be no statistically significant 12 month follow up minus pre-treatment 
differences across the four treatment groups in the mean total number of minutes of sleep (TST); 
Hypothesis 9e. There will be no statistically significant 12 month follow up minus pre-treatment 
differences across the four treatment groups in the mean total number of minutes of sleep divided by the 
total number of minutes in bed (SE). 
 
Hypothesis 10: Endurance of Treatment Effect on Insomnia Severity 
There will be no statistically significant 12 months follow up minus pre-treatment mean differences 
across the four treatment groups in insomnia severity as measured by the Insomnia Severity Index (ISI). 
 
Hypothesis 11: Endurance of Treatment Effect on Insomnia Diagnosis 
There will be no statistically significant chi square 12 month follow up minus pre-treatment mean 
differences across the four treatment groups in the percentage of subjects who meet DSM-5 criteria for 
780.52 Insomnia Disorder across time (pre-treatment; post-treatment; 12 month follow-up).  
 
Hypothesis 12: Endurance of Treatment Effect on Sleep Satisfaction Measures 
There will be no statistically significant overall 12 month follow up minus post-treatment differences 
across the four treatment groups in overall satisfaction/ dissatisfaction with sleep using standardized sum 
scores for data from subjects across the five likert scale measures of satisfaction/dissatisfaction on the 
Self Report Sleep Measures.   
If ANOVA indicates a significant overall difference, pairwise t-tests will test the following hypotheses: 
Hypothesis 12a. There will be no statistically significant 12 month follow up minus post-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
ability to get to sleep at bedtime; 
Hypothesis 12b. There will be no statistically significant 12 month follow up minus post-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
frequency of awakenings after having initiated sleep; 

2 
Hypothesis 12c. There will be no statistically significant 12 month follow up minus post-treatment  mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
ability to return to sleep after awakenings during the night; 
Hypothesis 12d. There will be no statistically significant 12 month follow up minus post-treatment  mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
average quantity of sleep; 
Hypothesis 12e. There will be no statistically significant 12 month follow up minus post-treatment  mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
overall quality of sleep. 
 
Hypothesis 13: Endurance of Treatment Effect on Subjective Sleep Distress 
There will be no statistically significant 12 month follow up minus post-treatment mean differences 
across the four treatment groups in self report of extent of distress with sleep difficulty. 
 
Hypothesis 14: Endurance of Self Report Sleep Satisfaction Measures 
There will be no statistically significant overall 12 month follow up minus post-treatment differences 
across the four treatment groups in overall satisfaction/ dissatisfaction with sleep using standardized sum 
scores for data from subjects across the five likert scale measures of satisfaction/dissatisfaction on the 
Self Report Sleep Measures.   
If ANOVA indicates a significant overall difference, pairwise t-tests will test the following hypotheses: 
Hypothesis 14a. There will be no statistically significant 12 month follow up minus post-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
ability to get to sleep at bedtime; 
Hypothesis 14b. There will be no statistically significant 12 month follow up minus post-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
frequency of awakenings after having initiated sleep; 
Hypothesis 14c. There will be no statistically significant 12 month follow up minus post-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
ability to return to sleep after awakenings during the night; 
Hypothesis 14d. There will be no statistically significant 12 month follow up minus post-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
average quantity of sleep; 
Hypothesis 14e. There will be no statistically significant 12 month follow up minus post-treatment mean 
differences across the four treatment groups in self report of extent of satisfaction or dissatisfaction with 
overall quality of sleep. 
 
Hypothesis 15: Satisfaction with Treatment 
There will be no statistically significant differences across treatment types in post-treatment reported 
overall level of satisfaction with the treatment received as measured with a 5-point Likert Scale on the 
FEEDBACK QUESTIONNAIRE.  
 
Hypothesis 16: Likelihood to Recommend to Others 
 
There will be no statistically significant differences across treatment types in post-treatment reported level 
of likelihood to recommend to others the treatment received as measured with a 5-point Likert Scale on 
the FEEDBACK QUESTIONNAIRE.  
 
MISSING DATA 
All data measures will be reviewed upon receipt to ensure no data is missing. Subjects who have not 
completed the data measures and/or specific items will be asked to do so immediately upon the review 
having identified missing data.  In any situations in which important missing data cannot be gathered, the 
subject will be eliminated from the study.  It is anticipated that in effect 5-10% of subjects will not 

                                                                                                                                             
1 
complete 12 month follow-up.  These subjects will then be eliminated as relates to analyses involving 12 
month follow-up data. Statistical analyses will be conducted to determine whether those with missing data 
differ significantly from those without missing data using t test comparing the two groups on total scores 
on Insomnia Severity Index at pre-treatment as well as post-treatment. 
 
STATISTICS 
Repeated measures analysis of variance (2 X 4 ANOVA) will be used to test the Hypotheses 1-3, 5-10 
and  11-16.  Any statistically significant ANOVAs will be followed by pairwise t-test comparisons to 
identify between group differences.  Chi square will be used to test Hypotheses 4 and 11.  
 
SAFETY ANALYSIS 
In general the potential risks for participants are minimal.  The treatment approaches involved in related 
studies have been shown to be a safe procedure and in most of the published studies people who 
underwent these procedures did not report any harmful effects.   
Prospective participants will be informed that it is nonetheless possible you may experience some 
discomforts during the treatment.  These may include temporary decrease in time asleep and 
accompanying daytime drowsiness.  Some people may become anxious while initially following the 
treatment procedures, with increased worry about their sleep difficulty.  Anxiety and worry about sleep 
difficulty are in fact common among persons with insomnia.  Therefore identifying and addressing these 
possibilities will be directly addressed during the treatment, and participants will be given guidance about 
what to expect and how to manage should these discomforts occur. Prospective participants will also be 
informed that persons with certain medical illnesses, certain psychiatric illnesses or other sleep disorders 
may be at increased potential risk of exacerbation of that illness.  This is a possibility for participants with 
epilepsy, bipolar depression, parasomnia, obstructive sleep apnea or other illnesses which have excessive 
daytime sleepiness as a feature of the parent disorder.  The participant may (or may not) be assigned to a 
treatment which involves sleep restriction.  Sleep loss through sleep restriction may 
 
1) Lower the threshold for seizures in persons with epilepsy; 
2)  Precipitate mania in bipolar participants; 
3) Exacerbate parasomnias; 
4) Prevent adequate ventilation in patients with obstructive sleep apnea; and/or 
5) Aggravate the day time somnolence to the point where it is no longer safe for the participant to 
drive, operate machinery and/or make judgments that adequately promote their own and/or the 
safety and well-being of others. 
The risk is generally higher when these illnesses are untreated.  Prospective participants treated for any of 
these illnesses and interested in participating must have the written approval of their treatment provider in 
order to be eligible.  If any of these risks (1-5 above) occur during the study, the participant will be asked 
to immediately discontinue the sleep restriction, and an alternative treatment not involving sleep 
restriction will be offered.  The participant will also have the option of discontinuing the treatment if they 
prefer this to proceeding with the alternative treatment which does not involve sleep restriction. 
 
 
 
 
 
 
 
 
 

2 
9.0                                       INVESTIGATIONAL PLAN 
 
9.1               OVERALL STUDY DESIGN AND PLAN: DESCRIPTION 
 
                    TELEPHONE PRE-SCREENING 
 
A) Provide information about the study, what to expect and what is required if participating.  Use 
Informed Consent form as an outline and a reference.  Ask if the person has any questions. 
 
B) Assess: Inclusion and Exclusion Criteria 
            The definition of insomnia will be that of DSM-5.   
 
9.1.1            IN PERSON SCREENING AND DATA GATHERING 
 
Complete diagnostic interview per DSM-5.  To be eligible, the person must meet the DSM-5 
diagnostic criteria for 780.52 Insomnia Disorder. This includes a cumulative minimum average sum 
of 30 minutes or more of time spent, adding number of minutes of inability to initiate or return to 
sleep plus number of minutes of early morning awakening with inability to return to sleep. 
 
If the person does not meet diagnostic criteria, thank them for their interest and inform the person that 
they are not eligible. Provide the specific reason for ineligibility.  For example, the person may not meet 
one or more required aspect of the diagnostic criteria for Insomnia Disorder per DSM-5. 
 
If the person meets eligibility criteria and DSM-5 diagnostic criteria for insomnia disorder, provide the 
person with a copy of the Informed Consent form.  Have the person follow along as you read the form 
aloud in their presence. 
 
At the end of this process, if the person is still interested in participating, go through the Informed 
Consent Form (ICF) for Participants in Insomnia Study with the participant.  
 
9.1.2                 DSM-5 DIAGNOSTIC SCREENING INTERVIEW 
 
Once the Informed Consent form has been completed, the next step involves a diagnostic interview to 
assess for Insomnia Disorder. The Research Coordinator reads the bold print script to the prospective 
participant.  See DSM-5 Diagnostic Assessment Interview. 
 
QUESTIONNAIRE AND INVENTORIES 
 
Since this is a clinical research trial, we have a questionnaire and some inventories for you to 
complete as part of the initial data gathering.   
 
Here is the first one.  Give the person the Sleep Measures (SM) questionnaire. 
 
I recommend you use a pencil so you can erase if you make an error.  Do you need a pencil?   
Be sure the person has a comfortable place to write (a table top, for example). 
 
This is the first one.  Go ahead.  Take a few minutes to complete it.  I’m here if you have any 
questions. 
When the participant has completed the Sleep Measures (SM) questionnaire, check to ensure that all 
questions have been answered.  Be sure questions with numerous options (a-f; -3 to +3; etc.) are clearly 
answered. 

                                                                                                                                             
1 
 
Ask the person to complete the Insomnia Severity Index (ISI). 
 
This will give us important information about your insomnia. 
When the participant has completed the inventory, check to ensure that all questions have been answered 
clearly.  Check for ISI > or = 10. If not, the person is not eligible.  If still eligible, record their score. 
 
Ask the person to complete the Beck Depression Inventory (BDI). 
 
Depression may or may not be a factor for you.  However, this is a research study, and the 
researchers want to be able to assess whether the treatment effect differs by level of depression. 
When the participant has completed the BDI, check to ensure that all questions have been answered 
clearly.  Check for BDI > or = 29. If so, the person is not eligible.  If still eligible, record their score. 
 
Similarly explain and ask the person to complete the Beck Anxiety Inventory (BAI).  When the 
participant has completed the BAI, check to ensure that all questions have been answered clearly.  Check 
for BAI > or = 36. If so, the person is not eligible.  If still eligible, record their score. 
 
1. Goal Motivation Scale (GMS) 
2. Goal Motivation Scale-Insomnia (GMS-I) 
3. Self-Report Sleep Measures (SRSM) 
4. Clinical Global Impression (CGI) 
5. Clinical Global Impression – Severity scale (CGI-S)  
6. Quality of Life Enjoyment and Satisfaction (Q-LES)  
7. Columbia Suicide Severity Rating Scale (C-SSRS) 
 
Give the person an ActiWatch.  Ask them to read and sign the ActiWatch Liability Agreement.  Ask them 
to return the Actiwatch on the day of their first scheduled session with their treatment provider. 
 
Explain the treatment scheduling to the participant. Read the following aloud.  
It is after your initial meeting with the treatment provider that we will make a final decision about 
your eligibility.  This depends on the ActiWatch data and the opinion of the treatment provider 
whether you do or do not meet the diagnostic criteria for Insomnia Disorder.  I am not a clinician, 
and therefore I am not qualified to give a diagnosis. 
 
As a participant, if you are eligible after the first session, you will be expected to participate in five 
additional treatment sessions scheduled weekly on the same day of the week and at the same time 
each week as was your first session with the treatment provider.   
 
It will be very important that you arrive on time for each of the treatment sessions.  If you miss one 
of the scheduled sessions for any reason, you must reschedule that session with your treatment 
provider for later that day or on the next day. If not, you will be discontinued from the study.  The 
treatment provider may only be available at certain times, and you will be expected to flex to make 
up for the session you missed.  Only one such rescheduling is allowed.   
 
ASSIGNMENT TO TREATMENT AND SCHEDUILNG 
Each participant will be assigned a “Participant Number” (PN).  The first seven digits will identify the 
participant with date of birth followed by the first letter in their first name (given at birth).  Digits the first 
three digits will identify the participant.  The first participant assigned a PN will be 001.  The second 
participant assigned a PN will be 002, etc. The 4th digit will identify the participant’s gender (M/F).  The 
5th digit will identify the participant’s treatment type [1 = Focus of Attention (FOA); 2 = Cognitive 

2 
Behavior Therapy for Insomnia (CBT-I); 3 = Combination of FOA and CBT-I (Combined); and 4 = 
Placebo (Sleep Hygiene only).  Digits 5-6 will identify the primary study staff delivering the treatment.  
An example might be  01 = Brie Everard.  
 
The Research Coordinator will determine the scheduling.   
If you participate, your time commitment will include six one hour appointments with your study 
staff.  These appointments will be on a weekday day, at 11:00am, 12:00 noon or 2:00pm.   As a 
participant, you will be assigned to on weekday for a one hour appointment for six consecutive 
weeks.  Please put an X beside each time that works for you on each day.  
Monday @ 
   ___ 11:00am;      ____ 12:00 noon;      ____ 2:00pm 
Tuesday @         ____ 11:00am;      ____ 12:00 noon;      ____ 2:00pm 
Wednesday @    ____ 11:00am;      ____ 12:00 noon;      ____ 2:00pm 
Thursday  @      ____ 11:00am;      ____ 12:00 noon;      ____ 2:00p 
 
Treatment providers will be required to declare at least one and preferably two of these times (11am, noon 
and/or 2pm) as times they will be available to delivery treatment, given two week notice of a participant 
being assigned.  The Research Coordinator will make effort to inform each provider when it is likely they 
will be assigned a new participant. 
 
The Research Coordinator will inform the treatment provider one week in advance of a probably 
participant being assigned, also informing the treatment provider of the treatment to be utilized (FOA, 
CBT-I, Combined and Sleep Hygiene).  
 
The Research Coordinator will keep an Excel spread sheet in order to systematically assign subjects 
(participants) to treatment.  Participants will be randomly assigned to treatment and then assigned to the 
next treatment provider in a systematic, non-biased manner.  The first four treatment providers will be 
randomly designated by the Research Coordinator as the first, second, third or fourth treatment provider 
to be assigned the participant.  The first participant in the clinical trial will go to the provider declared 
first to be assigned.  The second participant in the clinical trial will go to the provider declared second to 
be assigned.  Similarly for assignment of a participant to the third and fourth provider.  The fifth 
participant will be assigned to the provider who had been randomly designated as the first to be assigned a 
participant.  The assignment will proceed, sixth participant to the provider who had been assigned the 
second participant in the study, etc.  The Research Coordinator will use Excel spread sheet in order to 
determine which treatment provider is next to be assigned a participant.  
 
At the end of the In Person Screening and Data Gathering, the Research Coordinator will inform the 
participant of the time and date of their first treatment session and the name of the treatment provider.   
 
The Research Coordinator will direct the participant to arrive a few minutes early and to check in at the 
front desk in the first floor reception area.  The participant will be told to tell the receptionist their name, 
the name of their treatment provider, and that they are receiving treatment for insomnia in the Insomnia 
Clinical Research Trial. 
 
The Research Coordinator will schedule the participant with one of the treatment providers.  The 
treatment will be at either 11:00am, 12 noon or 2:00pm depending on which one hour block of time that 
treatment provider has reserved for treatment delivery.  The Research Coordinator will schedule the initial 
session in Practice Fusion with 5 weekly repeats.  The Research Coordinator will then send an email to 
the treatment provider indicating the name of the client, the time and date on which the first session is 
scheduled, and the treatment the provider is to deliver (FOA, CBT-I, Combined and Sleep Hygiene). 
 
 

                                                                                                                                             
1 
 
CLINICAL PROCEDURES 
The study staff will follow the six session protocol for treatment delivery.  Each of the six sessions is 
scripted so as to provide standardization, and the study staff will generally be reading the script.  The first 
session is identical across all four treatments.  For specifics, see file folders entitled CBT-I, FOA, Combo 
and Sleep Hygiene. 
 
DATA GATHERING DURING TREATMENT 
Ongoing self-report data pertaining to the participant’s sleep using a Weekly Sleep Log. Weekly Sleep 
Logs will be completed by the participant and brought to each treatment session.  At the beginning of 
each session, the study staff will review the Weekly Sleep Log for completion.  After the treatment 
session has ended and during the same day, the study staff will forward the Weekly Sleep Log to the 
Research Coordinator.   
 
The Research Coordinator will enter the following information onto the DATA  SHEET: 
1. SL; Sleep Latency (time to fall asleep in minutes) 
2. NOA: Number of Awakenings 
3. WASO: Wake After Sleep Onset (in minutes) 
4. SL +  WASO (in minutes) 
5. TOB: Total Time Out of Bed in minutes 
6. TST: Total Sleep Time (in minutes) 
7. TIB: Time In Bed (total, in minutes) 
8. SE: Sleep Efficiency = TST/TIB (as a decimal) 
 
9.1.3                                 SAFETY FOLLOW UP PERIOD 
 
Coordinated and administered by Research Coordinator.  Completed after last treatment session; can be 
on that day but not before the treatment session; must be no later than one week after that date. 
 
FEEDBACK QUESTIONNAIRE: 
1. Beck Depression Inventory (BDI) 
2. Beck Anxiety Inventory (BAI) 
3. Insomnia Severity Index (ISI) 
4. Self-Report Sleep Measures (SRSM)  
5. Clinical Global Impression (CGI) 
6. Clinical Global Impression – Severity scale (CGI-S)  
7. Quality of Life Enjoyment and Satisfaction (Q-LES)  
8. Columbia Suicide Severity Rating Scale (C-SSRS) 
 
THREE MONTH FOLLOW UP: 
WEEKLY SLEEP LOG (WSL) 
Data entry completed for one week at each administration [At in person intake, each week during 
treatment and at 3, 6 and 12 months] 
[Each of the following is needed for data entry as an average for the last 7 nights] 
1. SL; Sleep Latency (time to fall asleep in minutes) 
2. NOA: Number of Awakenings 
3. WASO: Wake After Sleep Onset (in minutes) 
4. SL +  WASO (in minutes) 
5. TOB: Total Time Out of Bed in minutes 
6. WASO:  Waking Time After Sleep Onset in minutes 
7. TST: Total Sleep Time (in minutes) 

2 
8. TIB: Time In Bed (total, in minutes) 
9. SE: Sleep Efficiency = TST/TIB (as a percentage) 
10. Beck Depression Inventory (BDI) 
11. Beck Anxiety Inventory (BAI) 
12. Insomnia Severity Index (ISI) 
13. Self-Report Sleep Measures (SRSM) 
14. Clinical Global Impression (CGI) 
15. Clinical Global Impression – Severity scale (CGI-S)  
16. Columbia Suicide Severity Rating Scale (C-SSRS) 
 
SIX MONTH FOLLOW UP: 
This is the same as the THREE MONTH FOLLOW UP except that the following three are added. 
1. Beck Depression Inventory (BDI) 
2. Beck Anxiety Inventory (BAI) 
3. Insomnia Severity Index (ISI) 
4. Self-Report Sleep Measures (SRSM) 
5. Clinical Global Impression (CGI) 
6. Clinical Global Impression – Severity scale (CGI-S)  
7. Columbia Suicide Severity Rating Scale (C-SSRS) 
 
TWELVE MONTH FOLLOW UP: 
This is the same as the SIX MONTH FOLLOW UP adding the Feedback  
Questionnaire. 
1. Beck Depression Inventory (BDI) 
2. Beck Anxiety Inventory (BAI) 
3. Insomnia Severity Index (ISI) 
4. Self-Report Sleep Measures (SRSM) 
5. Clinical Global Impression (CGI) 
6. Clinical Global Impression – Severity scale (CGI-S)  
7. Columbia Suicide Severity Rating Scale (C-SSRS) 
 
A schematic of the study design is presented in Figure9.1-1. The Schedule of Evaluations is presented 
in Section 2.0. Detailed descriptions of each study visit can be found in Section 9.5.6. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                             
1 
 
 
 
 
 
FIDURE 9.1-1 
        STUDY DESIGN 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Follow up
Weekly Sleep 
Log
Randomization
Screening 
Pt w/ Insominia
Pt w/ Insominia
CBTI
CBTI
6 wks of Sleep diary 
completion for 6 
sessions
6 wks of Sleep diary 
completion for 6 
sessions
Complete sleep diary 
in 3,6,12 months 
(Phone calls)
Complete sleep diary 
in 3,6,12 months 
(Phone calls)
FOA
FOA
6 wks of Sleep diary 
completion for 6 
sessions
6 wks of Sleep diary 
completion for 6 
sessions
Complete sleep diary 
in 3,6,12 months 
(Phone calls)
Complete sleep diary 
in 3,6,12 months 
(Phone calls)
FOA+CBTI
FOA+CBTI
6 wks of Sleep diary 
completion for 6 
sessions
6 wks of Sleep diary 
completion for 6 
sessions
Complete sleep diary 
in 3,6,12 months 
(Phone calls)
Complete sleep diary 
in 3,6,12 months 
(Phone calls)
Sleep hiegene only
Sleep hiegene only
6 wks of Sleep diary 
completion for 6 
sessions
6 wks of Sleep diary 
completion for 6 
sessions
Complete sleep diary 
in 3,6,12 months 
(Phone calls)
Complete sleep diary 
in 3,6,12 months 
(Phone calls)

2 
9.2 
         DISCUSSION OF STUDY DESIGN 
This is a randomized, open label, sleep hygiene, controlled, 6-week study to compare the efficacy of four 
(CBT-I, FOA, Combined CBT-I and FOA and Sleep Hygiene) different behavioral approaches for the 
treatment of adult subjects with insomnia. In this study, investigators will enroll patients, male and female, 
who are 18 or older to 72 years. Insomnia Severity Index > or = 10 and meet diagnostic criteria for Insomnia 
Disorder per DSM-5 willing and able to sign Informed consent form not planning on moving away from 
the area for the subsequent 12 weeks. In this study, safety and efficacy assessments are included during 
every visit to determine adequacy of response, safety, and tolerability. 
 
9.3                                  SLECTION OF STUDY POPULATIONS 
 
Inclusion/Exclusion criteria to be assessed at Screening (Visit 1) and Every Visit (Visit 2, 3, 4, 5, 6, 7, 
8, 9, 10 and 11) 
9.3.1                                  INCLUSION CRITERIA  
All potential participants must meet these inclusion criteria:  
1. Both genders 
2. Age ≥ 18 to 72 years 
3. Insomnia Severity Index > or = 10 
4. Meet diagnostic criteria for Insomnia Disorder per DSM-5 
5. Be willing and able to sign Informed consent form 
6. Not planning on moving away from the area for the subsequent 12 weeks. 
 
9.3.2                                    EXCLUSION CRITERIA 
Participants who answer “yes” to any of the following will be excluded: 
1. Females who are lactating or who are pregnant  
2. Night shift workers, and individuals who nap 3 or more times per week over the preceding month  
3. Consumption of caffeine beverages (i.e. tea, coffee, or cola) comprising usually more than 5 cups 
or glasses per day  
4. Participation in another trial for insomnia 
5. Persons unable to complete the study questionnaires and psychological tests 
6. Persons who are unable to participate for the entire duration of the study, or in the opinion of the 
investigators, are likely to be non-compliant with the obligations inherent in the trial participation 
7. Persons self-describing with severe anxiety or severe depression 
a. (BDI score of 29 or higher) or severe anxiety (BAI score of 36 or higher). 
8. Persons with a history of epilepsy, seizures, or dementia  
9. Any significant, severe or unstable, acute or chronically progressive medical or surgical condition  
10. Serious head injury or stroke within the past year 
11. Current alcohol or substance abuse/dependence (must have >90 days of sobriety) 
12. Presence of other neurological disorders (e.g., multiple sclerosis, Parkinson's Disease) 
13. Presence of an untreated or unstable medical or psychiatric comorbid condition (e.g., major 
depressive disorder or psychotic disorder requiring admission within the last two years).  People 
using psychotropic medication, hypnotic or sedative medications may be included if they are on a 
stable dosage for the last 2 months prior to the study, if the dose remains stable throughout the 
study, and if the medication is judged to not interfere with the study outcomes. 
14. Currently on medications known to produce insomnia (e.g., stimulants) 
15. Sleep apnea (AHI >15) or previous diagnosis of.   Study participants who use a continuous positive 
airway pressure (CPAP) device for sleep apnea will be eligible for participation if they are below 
the apnea/hypopnea cutoff while using CPAP and agree to use the device during study participation. 
16. If the person not eligible per inclusion and exclusion criteria, thank the person for their interest 
and inform them that they are not eligible.  Also inform the person that regardless, they still have 

                                                                                                                                             
1 
the option of seeing a health care provider at their own initiative and under whatever financial 
agreement they may establish with that health care provider (insurance or otherwise). 
17. If the person is eligible and is interested in being considered, schedule the initial in person 
screening interview and data gathering. 
 
9.3.3 
REMOVAL OF PATIENTS FROM THERAPY OR ASSESSMENT  
 
A premature discontinuation will occur when a patient who signed the ICF ceases participation in the 
study, regardless of circumstances, before the completion of the study visits and procedures. Patients can 
be prematurely discontinued from the study after careful consideration for one of the following reasons: 
 
1. Screen failure (failure to meet inclusion/exclusion criteria or pregnancy) 
2. Pregnancy 
3. Withdrawal of consent 
4. Lack of efficacy 
5. Protocol violation 
6. Noncompliance with treatment plan 
7. Lost to follow-up 
8. Study terminated by Sponsor 
9. Study center terminated by Sponsor 
10. Other 
 
All randomized patients who prematurely discontinue from the study, regardless of cause, should be seen 
for a final assessment at an Early Termination (ET) Visit. A final assessment will be defined as completion 
of the evaluations scheduled for all patients at Visit 8. All patients discontinuing the study prematurely 
should enter the 1-week safety follow-up period (Visit 8: ET). 
Patients who discontinue from the study and do not return to the study center for final assessments must be 
requested in writing to return to the study center for a final assessment (Visit 8). A copy of the letter, 
together with the source documentation, will be kept in the Investigator‘s files. The reason for premature 
discontinuation from the study will be recorded on the Study Termination Page of the eCRF. Study center 
staff will be contacted by the Sponsor after each premature discontinuation to ensure proper 
characterization of the reason for discontinuation is captured. 
 
9.3.4 
        PATIENT REPLACEMENT PROCEDURES 
 
Patients in this study who prematurely discontinue treatment will not be replaced. 
 
9.4 
                         TREATMENTS 
 
Patients meeting the eligibility criteria at the end of Visit 2 (Baseline) will be randomized in open label, 
sleep hygiene controlled 6-week study fashion to compare the efficacy of 1 of 4 treatment groups: CBT-I, 
FOA, Combined CBT-I and FOA and Sleep Hygiene (Placebo) different behavioral approaches for the 
treatment of adult subjects with insomnia. 
 
9.4.1            ASSIGNMENT TO TREATMENT AND SCHEDUILNG 
 
Each participant will be assigned a “Participant Number” (PN).  The first seven digits will identify the 
participant with date of birth followed by the first letter in their first name (given at birth).  Digits the first 
three digits will identify the participant.  The first participant assigned a PN will be 001.  The second 
participant assigned a PN will be 002, etc. The 4th digit will identify the participant’s gender (M/F).  The 

2 
5th digit will identify the participant’s treatment type [1 = Focus of Attention (FOA); 2 = Cognitive Behavior 
Therapy for Insomnia (CBT-I); 3 = Combination of FOA and CBT-I (Combined); and 4 = Placebo (Sleep 
Hygiene only).  Digits 5-6 will identify the primary study staff delivering the treatment.  An example might 
be 01 = Brie Everard.  
 
9.4.2     METHOD OF ASSIGNING PATIENTS TO TREATMENT GROUPS 
 
The Research Coordinator will determine the scheduling: 
If you participate, your time commitment will include six one hour appointments with your study 
staff.  These appointments will be on a weekday day, at 11:00am, 12:00 noon or 2:00pm.  As a 
participant, you will be assigned to on weekday for a one hour appointment for six consecutive weeks.  
Please put an X beside each time that works for you on each day.  
 
Monday@       ____ 11:00am;      ____ 12:00 noon;       ____ 2:00pm 
Tuesday@       ____ 11:00am;      ____ 12:00 noon;        ____ 2:00pm 
Wednesday@  ____ 11:00am;      ____ 12:00 noon;        ____ 2:00pm 
Thursday@     ____ 11:00am;      ____ 12:00 noon;         ____ 2:00p 
 
Treatment providers will be required to declare at least one and preferably two of these times (11am, noon 
and/or 2pm) as times they will be available to delivery treatment, given two week notice of a participant 
being assigned.  The Research Coordinator will make effort to inform each provider when it is likely they 
will be assigned a new participant. 
 
The Research Coordinator will inform the treatment provider one week in advance of a probably participant 
being assigned, also informing the treatment provider of the treatment to be utilized (FOA, CBT-I, 
Combined and Sleep Hygiene).  
 
The Research Coordinator will keep an Excel spread sheet in order to systematically assign subjects 
(participants) to treatment.  Participants will be randomly assigned to treatment and then assigned to the 
next treatment provider in a systematic, non-biased manner.  The first four treatment providers will be 
randomly designated by the Research Coordinator as the first, second, third or fourth treatment provider to 
be assigned the participant.  The first participant in the clinical trial will go to the provider declared first to 
be assigned.  The second participant in the clinical trial will go to the provider declared second to be 
assigned.  Similarly for assignment of a participant to the third and fourth provider,   the fifth participant 
will be assigned to the provider who had been randomly designated as the first to be assigned a participant.  
The assignment will proceed, sixth participant to the provider who had been assigned the second participant 
in the study, etc.  The Research Coordinator will use Excel spread sheet in order to determine which 
treatment provider is next to be assigned a participant.  
 
At the end of the In Person Screening and Data Gathering, the Research Coordinator will inform the 
participant of the time and date of their first treatment session and the name of the treatment provider.   
 
The Research Coordinator will direct the participant to arrive a few minutes early and to check in at the 
front desk in the first floor reception area.  The participant will be told to tell the receptionist their name, 
the name of their treatment provider, and that they are receiving treatment for insomnia in the Insomnia 
Clinical Research Trial. 
 
The Research Coordinator will schedule the participant with one of the treatment providers.  The treatment 
will be at either 11:00am, 12 noon or 2:00pm depending on which one hour block of time that treatment 
provider has reserved for treatment delivery.  The Research Coordinator will schedule the initial session in 
Practice Fusion with 5 weekly repeats.  The Research Coordinator will then send an email to the treatment 

                                                                                                                                             
1 
provider indicating the name of the client, the time and date on which the first session is scheduled, and the 
treatment the provider is to deliver (FOA, CBT-I, Combined and Sleep Hygiene). 
 
9.4.3                               CLINICAL PROCEDURES 
The study staff will follow the six session protocol for treatment delivery.  Each of the six sessions is 
scripted so as to provide standardization, and the study staff will generally be reading the script.  The first 
session is identical across all four treatments.  For specifics, see file folders entitled CBT-I, FOA, Combo 
and Sleep Hygiene. 
 
9.4.4                   DATA GATHERING DURING TREATMENT 
Ongoing self-report data pertaining to the participant’s sleep using a Weekly Sleep Log. Weekly Sleep Logs 
will be completed by the participant and brought to each treatment session.  At the beginning of each 
session, the study staff will review the Weekly Sleep Log for completion.  After the treatment session has 
ended and during the same day, the study staff will forward the Weekly Sleep Log to the Research 
Coordinator.   
 
The Research Coordinator will enter the following information onto the DATA SHEET: 
1. SL; Sleep Latency (time to fall asleep in minutes) 
2. NOA: Number of Awakenings 
3. WASO: Wake After Sleep Onset (in minutes) 
4. SL +  WASO (in minutes) 
5. TOB: Total Time Out of Bed in minutes 
6. TST: Total Sleep Time (in minutes) 
7. TIB: Time In Bed (total, in minutes) 
8. SE: Sleep Efficiency = TST/TIB (as a decimal) 
 
9.4.5                                  END OF TREATMENT 
 
SAFETY FOLLOW UP PERIOD 
Coordinated and administered by Research Coordinator.  Completed after last treatment session; can be on 
that day but not before the treatment session; must be no later than one week after that date. 
 
FEEDBACK QUESTIONNAIRE: 
1. Beck Depression Inventory (BDI) 
2. Beck Anxiety Inventory (BAI) 
3. Insomnia Severity Index (ISI) 
4. Self Report Sleep Measures (SRSM)  
5. Clinical Global Impression (CGI) 
6. Clinical Global Impression – Severity scale (CGI-S)  
7. Quality of Life Enjoyment and Satisfaction (Q-LES)  
8. Columbia Suicide Severity Rating Scale (C-SSRS) 
 
THREE MONTH FOLLOW UP: 
WEEKLY SLEEP LOG (WSL) 
Data entry completed for one week at each administration [At in person intake, each week during treatment 
and at 3, 6 and 12 months] 
[Each of the following is needed for data entry as an average for the last 7 nights] 
1. SL; Sleep Latency (time to fall asleep in minutes) 
2. NOA: Number of Awakenings 
3. WASO: Wake After Sleep Onset (in minutes) 
4. SL +  WASO (in minutes) 

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5. TOB: Total Time Out of Bed in minutes 
6. WASO:  Waking Time After Sleep Onset in minutes 
7. TST: Total Sleep Time (in minutes) 
8. TIB: Time In Bed (total, in minutes) 
9. SE: Sleep Efficiency = TST/TIB (as a percentage) 
10. Beck Depression Inventory (BDI) 
11. Beck Anxiety Inventory (BAI) 
12. Insomnia Severity Index (ISI) 
13.  Self Report Sleep Measures (SRSM) 
14. Clinical Global Impression (CGI) 
15. Clinical Global Impression – Severity scale (CGI-S)  
16. Columbia Suicide Severity Rating Scale (C-SSRS) 
 
SIX MONTH FOLLOW UP: 
This is the same as the THREE MONTH FOLLOW UP except that the following three are added. 
1. Beck Depression Inventory (BDI) 
2. Beck Anxiety Inventory (BAI) 
3. Insomnia Severity Index (ISI) 
4. Self Report Sleep Measures (SRSM) 
5. Clinical Global Impression (CGI) 
6. Clinical Global Impression – Severity scale (CGI-S)  
7. Columbia Suicide Severity Rating Scale (C-SSRS) 
 
TWELVE MONTH FOLLOW UP: 
This is the same as the SIX MONTH FOLLOW UP adding the Feedback Questionnaire. 
 
1. Beck Depression Inventory (BDI) 
2. Beck Anxiety Inventory (BAI) 
3. Insomnia Severity Index (ISI) 
4. Self Report Sleep Measures (SRSM) 
5. Clinical Global Impression (CGI) 
6. Clinical Global Impression – Severity scale (CGI-S)  
7. Columbia Suicide Severity Rating Scale (C-SSRS) 
 
A schematic of the study design is presented in Figure 9.1-1. The Schedule of Evaluations is presented 
in Section 2.0. Detailed descriptions of each study visit can be found in Section 9.5.3. 
 
9.4.6 
    SELECTION AND TIMING OF SIX SESSION TREATMENT  
                              FOR EACH PATIENT  
The study staff will follow the six sleep hygiene treatment session at visits 2, 3, 4, 5, 6 and 7.  Each of the 
six sessions is scripted so as to provide standardization, and the study staff will generally be reading the 
script.  The first session is identical across all four treatments.  For specifics, see file folders entitled CBT-
I, FOA, Combo and Sleep Hygiene. 
 
9.4.6.1                               SCREENING PERIOD 
 
At Screening (Visit 1) after written consent is obtained, patients enter a screening period of up to 14 
days. No treatment is administered during the screening period.  
 
 

                                                                                                                                             
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9.4.6.2              RANDAMIZATION OPEN LABEL SLEEP HYGIENE CONTROLLED   
SIX WEEK STUDY TREATMENT PERIOD 
 
Patients who meet all eligibility criteria at Screening (Visit 1) and who continue to meet all the eligibility 
criteria for participation in the study at the Baseline Visit (Visit 2) will be assigned a “Participant Number” 
(PN).  The first seven digits will identify the participant with date of birth followed by the first letter in their 
first name (given at birth).  Digits the first three digits will identify the participant.  The first participant 
assigned a PN will be 001.  The second participant assigned a PN will be 002, etc. The 4th digit will identify 
the participant’s gender (M/F).  The 5th digit will identify the participant’s treatment type [1 = Focus of 
Attention (FOA); 2 = Cognitive Behavior Therapy for Insomnia (CBT-I); 3 = Combination of FOA and 
CBT-I (Combined); and 4 = Placebo (Sleep Hygiene only).  Digits 5-6 will identify the primary study staff 
delivering the treatment.  An example might be  01 = Brie Everard.  
 
9.4.6.3                          SAFETY FOLLOW-UP PERIOD 
 
Patients who complete 6 weeks of randomized, open label sleep hygiene controlled treatment are eligible 
to enter the safety follow-up period. Patients who discontinue the study prematurely should also enter the 
safety follow-up period. No sleep hygiene treatment session is administered during the safety follow-up 
period. 
 
9.4.7                              CONCOMITANT MEDICATIONS 
 
A list of example medications as concomitant medications is provided in Appendix III. Medication 
history (psychotropic medication history during the previous 5 years and all other medications during 
the past 12 months) will be recorded at Screening (Visit 1) in the eCRF. Thereafter, any changes in 
concomitant medications or any new medications added will be recorded in the eCRF. 
 
9.4.7.1                     PERMITED MEDICATIONS/TREATMENTS 
 
Therapy considered necessary for the patient's welfare may be given at the discretion of the Investigator. 
If the permissibility of a specific medication/treatment is in question, please contact the Sponsor. 
 
FOR INSOMNIA: 
Eszopiclone, zolpidem, zolpidem extended-release, zopiclone or zaleplon for insomnia may be 
continued provided the medication has been used in a consistent manner for 4 weeks prior to 
enrollment.  Following enrollment, these medications may also be introduced in patients not 
previously treated as necessitated by insomnia that emerges or worsens during the study.  
In these patients, the medications will be permitted up to 3 times a week at the following doses 
(not permitted within 8 hours of efficacy measures): 
1. Zolpidem (maximum of 10 mg/day) 
 
2. Zolpidem extended release (maximum of 12.5 mg/day) 
 
3. Zaleplon (maximum of 20 mg/day) 
 
4. Eszopiclone (maximum of 3 mg/day) 
 
5. Zopiclone (maximum of 7.5 mg/day) 
 
6. Suvorexant (maximum of 10 mg/day) 
 

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These medications must be administered before bedtime as recommended in their prescribing 
information. The medication must be documented on the concomitant medications page of 
the eCRF. No such medication is permitted within 8 hours of psychiatric or neurological 
assessments. 
 
FOR ANXIETY OR AGITATION: 
Episodic use of benzodiazepines up to approximately 2 mg/day lorazepam equivalent dose and for 
up to 3 consecutive days at a time may be given for anxiety-related conditions and agitation (not 
permitted within 8 hours of efficacy assessments). 
 
9.4.7.2                          PROHIBITED MEDICATIONS/TREATMENTS 
 
The decision to administer a prohibited medication/treatment is done with the safety of the patient as 
the primary consideration. When possible, the Sponsor should be notified before the prohibited 
medication/treatment is administered. 
 
The following medications are prohibited: 
1. Antipsychotics 
 
2. Antidepressants  
 
3. Stimulants 
 
 
4. Anticonvulsants/mood stabilizers 
 
5. Dopamine-releasing drugs or dopamine agonists 
 
6. Psychotropic drugs not otherwise specified (including herbal products and certain nutritional 
supplements) 
 
Appropriate washout of prohibited medications is to be conducted at the discretion of the 
Investigator and should begin as soon as practical following consent and screening. 
 
9.4.8                                 OTHER RESTRCTIONS 
 
9.4.8.1             ALCOHOL 
It is recommended that patients abstain from alcohol consumption during the study. 
  
9.4.9                MONITORING TREATMENT COMPLIANCE 
 
Six Week treatment session compliance during any period will be closely monitored by capturing the date 
and time of each visit. If a scheduled visit does not occur, the Sponsor must be notified and the reason 
captured in the eCRF. 
 
 
 
 
 
 
 

                                                                                                                                             
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9.4.10                    TREATMENT AFTER DISCONTINUATION 
 
Patients whose sleep symptoms worsen or are determined by the Investigator not to be adequately 
controlled prior to completing the randomization six week study period will be allowed to discontinue 
the study and start appropriate treatment at the Investigator‘s discretion. This new treatment will not be 
provided by the Sponsor. Patients who initiate a new treatment must be discontinued from the study. 
 
9.5 
EFFICACY AND SAFETY VARIABLES 
 
9.5.1 
DIAGNOSTIC AND EFFICACCY ASSESSMENTS 
 
9.5.1.1 
DIAGNOSTIC ASSESSMENTS 
 
Complete diagnostic interview per DSM-5.  To be eligible, the person must meet the DSM-5 
diagnostic criteria for 780.52 Insomnia Disorder. This includes a cumulative minimum average sum 
of 30 minutes or more of time spent, adding number of minutes of inability to initiate or return to 
sleep plus number of minutes of early morning awakening with inability to return to sleep. 
If the person does not meet diagnostic criteria, thank them for their interest and inform the person that they 
are not eligible. Provide the specific reason for ineligibility.  For example, the person may not meet one or 
more required aspect of the diagnostic criteria for Insomnia Disorder per DSM-5. 
If the person meets eligibility criteria and DSM-5 diagnostic criteria for insomnia disorder, provide the 
person with a copy of the Informed Consent form.  Have the person follow along as you read the form aloud 
in their presence. 
At the end of this process, if the person is still interested in participating, go through the Informed Consent 
Form for Participants in Insomnia Study with the participant.  
 
9.5.1.2 
          EFFICACY ASSESMENTS 
 
The efficacy assessments (CGI -S) will be administered by a psychiatrist, doctoral level clinical 
psychologist, or other study staff who has extensive professional training and experience in the 
diagnosis of mental illness and who meets the training requirements and qualifications standards set 
by the Sponsor. 
 
9.5.1.3                 THE CLINICAL GLOBAL IMPRESSIONS-SEVERITY 
 
The CGI-S (Guy, 1976) is a clinician-rated scale used to rate the severity of the patient‘s current state of 
mental illness compared with a patient population with MDD. The patient will be rated on a scale from 1 
to 7 with 1 indicating a —normal, “not at all ill” and 7 indicating —among the most extremely ill 
patients.“ The CGI-S will be administered by the Investigator or a sub-investigator with extensive 
professional training and experience in assessing mental illness and qualifications standards set by the 
Sponsor and rater training vendor. 
 
9.5.2 
               SAFETY ASSESMENTS 
 
Patients must be evaluated by a physician or an appropriately trained health care professional at 
every visit and the evaluation must be documented.  
 
 
9.5.2.1 
                    ADVERSE EVENTS 
 
An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a 
pharmaceutical product and which does not necessarily have to have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal 

2 
laboratory finding, for example), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the medicinal product (ICH-E2A). 
For the purpose of the study center‘s data collection responsibilities, any untoward event that was 
reported from the time the patient signed the ICF until 30 days after the final protocol-defined study visit 
or the last known dose of IP (if the final visit does not occur) is to be considered an AE. 
  
EXAMPLES OF AEs ARE AS FOLLOWS: 
1. Changes in the general condition of the patient 
2. Subjective symptoms offered by or elicited from the patient 
3. Objective signs observed by the Investigator or other study center personnel 
4. All diseases that occur after signing informed consent, including any change in severity or 
frequency of pre-existing disease 
5. All clinically relevant abnormalities in laboratory values or clinically relevant physical 
findings that occur during the study schedule 
 
9.5.2.2 
                     CAUSALITY ASSESSMENT 
 
The causality assessment must be recorded on the appropriate AE reporting page of the patient‘s eCRF. 
Causal relationship must be assessed by answering the following question: 
Is there a reasonable possibility the sleep study treatment caused the event? 
Yes: 
There is evidence to suggest a causal relationship between the sleep study treatment and AE, 
i.e.: 
1. There is a reasonable temporal relationship between the IP and the event, and/or 
 
2. The event is unlikely to be attributed to underlying/concurrent disease or other factors, and/or 
 
3. Positive de-challenge and/or re-challenge exist 
 
No: 
There is no evidence to suggest a causal relationship between the sleep study treatment 
and AE, i.e.: 
 
1. There is no reasonable temporal relationship between the IP and the event, or 
 
2. The patient did not take the IP, or 
 
3. The event is likely to be attributed to underlying/concurrent disease or other factors, or 
 
4. The event is commonly occurring in the (study) population independent of IP exposure 
 
9.5.2.3 
               SEVERITY ASSESMENT 
 
The Investigator will provide an assessment of the severity of each AE by recording a severity rating 
on the appropriate AE reporting page of the patient‘s eCRF. Severity, which is a description of the 
intensity of manifestation of the AE, is distinct from seriousness, which implies a patient outcome or 
AE-required treatment measure associated with a threat to life or functionality (Section 9.5.2.4). 
Severity will be assessed according to the following scale: 
Mild:             A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual 
activities of daily living. 

                                                                                                                                             
1 
Moderate:        A type of AE that is usually alleviated with additional specific therapeutic intervention. 
The event interferes with usual activities of daily living, causing discomfort, but poses 
no significant or permanent risk of harm to the research participant. 
Severe: 
A type of AE that interrupts usual activities of daily living, or significantly affects 
clinical status, or may require intensive therapeutic intervention. 
 
9.5.2.4 
              SERIOUS ADVERSE EVENTS 
 
An SAE is any untoward medical occurrence that at any dose: 
1. Results in death 
2. Is life threatening 
3. Requires inpatient hospitalization or prolongation of existing hospitalization 
4. Results in persistent or significant disability/incapacity, or 
5. Is a congenital anomaly/birth defect 
 
Important medical events that may not result in death, belief threatening, or require hospitalization may 
be considered serious when, based on appropriate medical judgment, they may jeopardize the patient and 
may require medical or surgical intervention to prevent one of the outcomes listed in this definition. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in patient hospitalization, 
or the development of IP dependency or drug abuse. 
Emergency room visits that do not result in hospitalization should be evaluated for one of the other 
serious outcomes to determine whether they qualify as SAEs. 
Preplanned hospitalizations (e.g, elective procedures for pre-existing conditions that did not worsen, 
such as cosmetic surgery and hysterectomy) are excluded from SAE reporting. 
 
9.5.2.5 
   REPORTING ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS  
 
At each visit, patients are to be queried regarding any AEs or SAEs that have occurred since the previous 
visit. Patients will be asked to volunteer information with a non leading question such as, —How do you 
feel since your last visit?“ Study center personnel will record all pertinent information in the patient‘s 
eCRF. All AEs must be recorded on the appropriate AE reporting page of the patient‘s eCRF whether or 
not they are considered causally related to the sleep study treatment.. 
For every AE, the Investigator must: 
 
1. Provide an assessment of the seriousness of the event (ie, is it an SAE?), as well as the severity 
and casual relationship 
 
2. Document all actions taken with regard to the IP 
 
3. Detail any other treatment measures taken for the AE 
 
4. Document the outcome of the AE 
 
In addition, patients are to be reminded, as described in the ICF and in accordance with Section 9.5.2.1, 
to notify study center personnel of any AEs occurring during the 30-day poststudy period. Any AEs 
reported by the patient (or patient representative) during this period are to be recorded in original source 
documents. AEs are also to be recorded in the eCRF if at least one of the following conditions is met: 1) 
the event meets the criteria for an SAE (see Sections 9.5.2.4 and 9.5.2.5), and/or 3) the event is judged by 
the Investigator to be potentially causally related to sleep study treatment. 

2 
Any AEs that are ongoing at the time of the final protocol-defined study visit will be followed until the 
condition returns to pre-study status, has resolved or stabilized, or can be explained as being unrelated 
to the sleep study treatment. If a follow-up visit is deemed necessary for appropriate safety 
surveillance, it will take place within 30 days of the final protocol-defined study visit. 
 
9.5.2.6           COLUMBIA SUICIDE SEVERITY RATING SCALE 
 
The C-SSRS is an instrument that reports the severity of both suicidal ideation and behavior. 
Suicidal ideation is classified on a 5-item scale: 1 (wish to be dead), 2 (nonspecific active suicidal 
thoughts), 3 (active suicidal ideation with any methods [not plan] without intent to act), 4 (active 
suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation 
with specific plan and intent). The C-SSRS also captures information about the intensity of 
ideation, specifically the frequency, duration, controllability, deterrents, and reasons for the most 
severe types of ideation. Suicidal behavior is classified on a 5-item scale: 0 (no suicidal behavior), 
1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), and 4 (actual 
attempt). More than 1 classification can be selected provided they represent separate episodes. 
For actual attempts only, the actual or potential lethality is classified for the initial, most lethal, 
and most recent attempts. The C-SSRS will be completed at all study visits. At Screening (Visit 
1), the C-SSRS will be completed for the patient‘s lifetime history of suicidal ideation and 
behavior (Appendix X). At all other visits, the C-SSRS will be completed for ideation and 
behavior since the previous visit (Appendix XI). The C-SSRS will be evaluated and signed at 
each visit by a qualified staff member (i.e, the Investigator or designee that has extensive 
professional training and experience in assessing mental illness), before the patient leaves the 
study center. 
 
9.5.3                            SCHEDUAL OF ASSESSMENT 
 
The schedule of study procedures and assessments is tabulated by visit in the Schedule of Evaluations in 
Section 2.0. The descriptions of the procedures to be performed at each visit are provided in the 
following sections. Upon providing written informed consent, patients enter a screening period of up to 
14 days. Following the screening period, patients enter the randomized, open label , sleep hygiene 
controlled six- week study to compare the efficacy of four (CBT-I, FOA, Combined CBT-I and FOA 
and Sleep Hygiene) different behavioral approaches for the treatment of adult subjects with insomnia.  
 
9.5.3.1        Visit 1 (Screening) 
 
At Screening (Visit 1), study procedures will be reviewed with the patient, and documentation of 
informed consent will be obtained (Section 5.3). After informed consent is obtained, patients will be 
assigned a unique “Participant Number” (PN) (Section 5.0). A review of inclusion/exclusion criteria and 
other screening assessments will be conducted to determine the patient‘s eligibility for enrollment 
(Sections 9.3.1 and 9.3.2). 
 
At Screening (Visit 1), the following procedures will also be performed: 
1. Obtain and record medical (surgical, neurological), psychiatric history 
2. Obtain and record prior medication history, nondrug psychiatric treatment history, and 
current medication status 
3. Review of all inclusion/exclusion criteria 
4. Administer ISI (Insomnia Severity Index) 
5. Administer BAI (Beck Anxiety Inventory) 
6. Administer BDI (Beck Depression Inventory) 
7. Administer SRSM (Self Report Sleep Measures) 
8. Administer WSL (Weekly Sleep Log 

                                                                                                                                             
1 
9. Administer CGI-S (Clinical Global Impression –Severity Scale) 
10. Administer CGI (Clinical Global Impression) 
11. Administer Q-LES (Quality of Life Enjoyment and Satisfaction) 
12. Administer C-SSRS (Columbia-Suicide Severity Rating Scale) 
13. Review concomitant medications 
 
 
Schedule Visit 2 up to 14 days after Visit 1 
 
9.5.3.2                 Visit 2 (or Baseline Visit) 
 
The Baseline Visit 2 will be conducted up to 14 days after Screening (Visit 1) to determine whether the 
patient is eligible to continue into the randomization, open label, sleep hygiene controlled 6 week study 
treatment period. 
At the visit 2, the following procedures will be performed: 
1. Review of all inclusion/exclusion criteria 
2. Administer SRSM (Self Report Sleep Measures) 
3. Administer CGI-S (Clinical Global Impression –Severity Scale) 
4. Administer CGI (Clinical Global Impression) 
5. Administer C-SSRS (Columbia-Suicide Severity Rating Scale)  
6. Review and record AEs 
7. Eligible patients will be assigned an “Participant Number” (PN).   
 
Administer Randomization (must occur after all efficacy and safety assessments) 
Schedule Visit 3  
 
9.5.3.3                Visit 3 
 
At Visit 3, the following procedures will be performed: 
1. Review of all inclusion/exclusion criteria 
2. Administer SRSM (Self Report Sleep Measures) 
3. Administer CGI-S (Clinical Global Impression –Severity Scale) 
4. Administer CGI (Clinical Global Impression) 
5. Administer C-SSRS (Columbia-Suicide Severity Rating Scale)  
6. Review concomitant medications 
 
Schedule Visit 4  
 
 
9.5.3.4                Visit 4 
 
At Visit 4, the following procedures will be performed: 
1. Review of all inclusion/exclusion criteria 
2. Administer SRSM (Self Report Sleep Measures) 
3. Administer CGI-S (Clinical Global Impression –Severity Scale) 
4. Administer CGI (Clinical Global Impression) 
5. Administer C-SSRS (Columbia-Suicide Severity Rating Scale)  
6. Review concomitant medications 
 
Schedule Visit 5 
 
 
 

2 
9.5.3.5 
               Visit 5 
 
At Visit 5, the following procedures will be performed: 
1. Review of all inclusion/exclusion criteria 
2. Administer SRSM (Self Report Sleep Measures) 
3. Administer CGI-S (Clinical Global Impression –Severity Scale) 
4. Administer CGI (Clinical Global Impression) 
5. Administer C-SSRS (Columbia-Suicide Severity Rating Scale)  
6. Review concomitant medications 
 
Schedule Visit 6 
9.5.3.6 
                 Visit 6 
 
At Visit 6, the following procedures will be performed: 
1. Review of all inclusion/exclusion criteria 
2. Administer SRSM (Self Report Sleep Measures) 
3. Administer CGI-S (Clinical Global Impression –Severity Scale) 
4. Administer CGI (Clinical Global Impression) 
5. Administer C-SSRS (Columbia-Suicide Severity Rating Scale)  
6. Review concomitant medications 
 
Schedule Visit 7 
9.5.3.7 
                 Visit 7 
 
At Visit 7, the following procedures will be performed: 
1. Review of all inclusion/exclusion criteria 
2. Administer SRSM (Self Report Sleep Measures) 
3. Administer CGI-S (Clinical Global Impression –Severity Scale) 
4. Administer CGI (Clinical Global Impression) 
5. Administer C-SSRS (Columbia-Suicide Severity Rating Scale)  
6. Review concomitant medications 
 
Schedule Visit 8 (Follow up Period) 
9.5.3.8 
Visit 8 (1 Week Follow up Period) 
 
At Visit 8, the following procedures will be performed: 
1. Review of all inclusion/exclusion criteria 
2. Administer ISI (Insomnia Severity Index) 
3. Administer BAI (Beck Anxiety Inventory) 
4. Administer BDI (Beck Depression Inventory) 
5. Administer SRSM (Self Report Sleep Measures) 
6. Administer WSL (Weekly Sleep Log 
7. Administer CGI-S (Clinical Global Impression –Severity Scale) 
8. Administer CGI (Clinical Global Impression) 
9. Administer Q-LES (Quality of Life Enjoyment and Satisfaction) 
10. Administer C-SSRS (Columbia-Suicide Severity Rating Scale) 
 
Schedule Visit 9 (3 Months Follow up Period)  
 
9.5.3.9           Visit 9 (3 Months Follow up Period) 
 
At Visit 9, the following procedures will be performed: 
1. Review of all inclusion/exclusion criteria 

                                                                                                                                             
1 
2. Administer ISI (Insomnia Severity Index) 
3. Administer BAI (Beck Anxiety Inventory) 
4. Administer BDI (Beck Depression Inventory) 
5. Administer SRSM (Self Report Sleep Measures) 
6. Administer WSL (Weekly Sleep Log 
7. Administer CGI-S (Clinical Global Impression –Severity Scale) 
8. Administer CGI (Clinical Global Impression) 
9. Administer C-SSRS (Columbia-Suicide Severity Rating Scale) 
 
Schedule Visit 10 (6 Months Follow up Period) 
 
9.5.3.10          Visit 10 (6 Months Follow up Period) 
 
At Visit 10, the following procedures will be performed: 
1. Review of all inclusion/exclusion criteria 
2. Administer ISI (Insomnia Severity Index) 
3. Administer BAI (Beck Anxiety Inventory) 
4. Administer BDI (Beck Depression Inventory) 
5. Administer SRSM (Self Report Sleep Measures) 
6. Administer WSL (Weekly Sleep Log 
7. Administer CGI-S (Clinical Global Impression –Severity Scale) 
8. Administer CGI (Clinical Global Impression) 
9. Administer C-SSRS (Columbia-Suicide Severity Rating Scale) 
 
Schedule Visit 11 (12 Months Follow up Period) 
 
9.5.3.11              Visit 11 (12 Months Follow up Period) 
 
At Visit 11, the following procedures will be performed: 
1. Review of all inclusion/exclusion criteria 
2. Administer ISI (Insomnia Severity Index) 
3. Administer BAI (Beck Anxiety Inventory) 
4. Administer BDI (Beck Depression Inventory) 
5. Administer SRSM (Self Report Sleep Measures) 
6. Administer WSL (Weekly Sleep Log 
7. Administer CGI-S (Clinical Global Impression –Severity Scale) 
8. Administer CGI (Clinical Global Impression) 
9. Administer C-SSRS (Columbia-Suicide Severity Rating Scale) 
 
Any clinical findings obtained during the Follow-up Visit will be followed until the condition returns to 
pre-study status, has resolved or stabilized, or can be explained as being unrelated to sleep study 
treatment. A follow-up visit, if one should be necessary, will take place within 7 days of sleep study 
treatment termination. 
9.5.3.12 Unscheduled Visits 
 
Unscheduled visits can be performed if safety concerns arise and at the discretion of the Investigator. 
Additional examinations may be performed as necessary to ensure the safety and well-being of the 
patients during the study. 
 
 
 
 

2 
9.6 
DATA QUALITY ASSURANCE 
9.6.1 
DATA MONITORING 
 
Before any patient enters the study, a representative of the Sponsor will meet with the Investigator and 
the study center staff to review the procedures to be followed during the study. Manual data capture 
(MDC) functionality training is provided via computer-based training to train investigators and 
authorized designees on recording the data in the eCRFs using the MDC system. After the first patient is 
enrolled, the Sponsor representative, a Regional Site Manager or designee, will periodically monitor the 
progress of the study by conducting on-site visits. This Regional Site Manager or designee will review 
query status remotely, possibly warranting more frequent communication and/or study center visits with 
the Investigator and the study center staff. The Investigator will make available to the Regional Site 
Manager or designee source documents (written notes and electronic medical records, if used), signed 
consent forms, and all other study-related documents. The Investigator and the study center staff will be 
responsible for data entry of patient data into the eCRFs via the MDC system, resolving data queries 
generated via the MDC system and providing missing or corrected data. The Investigator or designee 
will be responsible for approving all changes performed on the data, and endorsing the patient data 
within the MDC system. This approval method will include applying an electronic signature linked to a 
uniquely assigned username and password that together will represent a traditional handwritten signature 
used in the past. 
 
9.6.2 
DATA RECORDING AND DOCUMENTATION 
 
Data collection will involve the use of the MDC (Manual data capture) system, to which only authorized 
personnel will have access. Patient‘s data are to be entered into the MDC system by the Investigator or 
designee using their assigned MDC user account. After data entry into the MDC system by the 
Investigator or designee, a combination of manual and programmatic edit checks will be used to review 
the data for completeness, logic, and adherence to study protocol. As a result of these edit checks, data 
monitoring, and reviews, queries may be electronically issued to the study center and should be answered 
electronically via the MDC system. Each query will carry identifying information (assigned username, 
date, and time) to assist the Sponsor and the Investigator on the origin of the data clarification request and 
the response provided by the Investigator. All data changes made to the patient‘s data via a data query 
will be approved by the Investigator prior to final database lock.  
After all data have been reviewed and all issues have been resolved, the database will be locked. All data 
collected in the context of this study will be stored and evaluated per regulatory requirements and 
applicable guidance for electronic records. Also, data will be stored and evaluated in such a way as to 
guarantee patient confidentiality in accordance with the legal stipulations applying to confidentiality of 
data. Study records (e.g, copies of eCRFs, laboratory reports, regulatory documents) will be retained at 
the study center, along with adequate source documentation, according to FDA and ICH requirements. 
All study records must be available for inspection by the Sponsor, its authorized representatives, the 
FDA, or other health authorities. 
 
9.6 
              STATISTICAL METHODS AND DETERMINATION OF 
SMAPLE SIZE 
9.7.1   SAMPLE SIZE 
It is estimated that 320 prospects will need to be screened in order to have 40 per group for a total of 160 
participants. 
 
9.7.2    ANALYSIS POPULATIONS 
1. Safety Population: will include all randomized subjects who meet eligibility criteria and meet with 
their treatment provider for session 1. 

                                                                                                                                             
1 
2. Intent-to-Treat Population: will include all subjects who meet with their  treatment provider for 
session 1 and for whom the treatment provider determines the subject meets diagnostic criteria for 
780.52 Insomnia Disorder. 
3. Pre-Protocol (PP) Population: will include all subjects who complete the 6 sessions of treatment 
as well as the 3 month, 6 month and 12 month follow up assessment.  It is estimated that 80% of 
those who complete session 1 will complete session 6.  It is estimated that 80% of those who 
complete session 6 will complete the 3 month, 6 month and 12 month follow up assessments.  This 
will result in 25 participants who will have completed the entire study. 
9.7.3         SAFAETY PARAMETERS 
 
Safety parameters comprise the C-SSRS. 
The number and percentage of patients with suicidal ideation or suicidal behavior as recorded on the C-
SSRS will be summarized by treatment group. The distribution of responses for most severe suicidal 
ideation and most severe suicidal behavior during the patient’s lifetime, during the treatment period, and 
during the safety follow-up period will also be presented by treatment group for the Safety Population. 
Supportive listings will be provided and will include the “Participant Number” (PN), lifetime history, 
and post baseline values. Intensity of suicidal ideation, suicidal behavior type, and lethality of suicidal 
behavior will also be included in these listings. A listing of all AEs occurring in patients who have 
suicidal ideation or suicidal behavior will also be provided. 
  
9.7.4                          COMPUTER METHODS 
 
Statistical analyses will be performed using version 9.3 (or newer) of SAS on a Linux operating 
system.   
9.8 
DATA AND SAFETY MONITORING BOARD 
 
The study will be conducted under the supervision of an independent DSMB to be chartered to review 
safety data at predetermined points during the study. The DSMB may also decide to meet and review 
safety data at other time points should it be deemed necessary. The DSMB is responsible for the ongoing 
review of safety data in the clinical study and for making recommendations concerning the continuation, 
modification, and termination of the study (FDA Guidance for Clinical Trial Sponsors: Establishment 
and Operation of Clinical Trial Data Monitoring Committees, March 2006). All analyses that are 
required to support the DSMB will be performed by an independent unblinded statistician not otherwise 
involved in the study. Details of the DSMB membership, meeting schedule, and data review and analysis 
will be documented in the DSMB Charter. 
Any amendment to this protocol will be provided to the Investigator in writing by the Sponsor. No 
protocol amendment may be implemented (with the exceptions noted below) before it has been approved 
by the IRB, and the signature page, signed by the Investigator, has been received by the Sponsor. If the 
protocol is amended to eliminate or reduce the risk to patients, the amendment may be implemented 
before IRB review and approval. However, the IRB must be informed in writing of such an amendment, 
and approval must be obtained within reasonable time limits. 
 
9.9           CHANGES IN THE COUNDUCT OF THE STUDY OR  PLANNED ANALYSIS 
 
Any amendment to this protocol will be provided to the Investigator in writing by the Sponsor. No 
protocol amendment may be implemented (with the exceptions noted below) before it has been approved 
by the IRB, and the signature page, signed by the Investigator, has been received by the Sponsor. If the 

2 
protocol is amended to eliminate or reduce the risk to patients, the amendment may be implemented 
before IRB review and approval. However, the IRB must be informed in writing of such an amendment, 
and approval must be obtained within reasonable time limits. 
 
 
 
9.10 
           PROTOCOL DEVIATIONS 
 
A protocol deviation is any change, divergence, or departure from the study design or procedures that 
is under the Investigator’s responsibility and oversight (as defined by regulations) without prior written 
IRB approval or favorable opinion of an appropriate amendment and that does not have a major impact 
on the patient‘s rights, safety, or well-being, or on the integrity and authenticity of the study data. 
Deviations may include, but are not limited to, departure from inclusion/exclusion criteria, duration of 
treatment, failure to perform the required assessments at specified time points, scheduling of visits not 
in accordance with specifications, or patient safety. Deviating from the protocol is permitted only if 
absolutely necessary for the safety or clinical management of the patients and must immediately be 
reported to the Sponsor. 
Protocol deviations must be reported to the Sponsor either verbally or electronically within 5 
working days from the day of discovery. 
An important protocol deviation is a form of protocol deviation that has a major impact on the patient‘s 
rights, safety, or well-being, or on the integrity and authenticity of the study data. Important protocol 
deviations must be reported to the Sponsor within 24 hours, if possible. The IRB must be notified 
within the time period dictated by the IRB associated with this study. 
 
10.0 
              STUDY SPONSORSHIP 
 
This study is sponsored by Puget Sound Psychiatry Center (PSPC) Bothell, WA. 
 
 
10.1 
             STUDY TERMINATION 
 
The Sponsor reserves the right to terminate the study in its entirety or at a specific study center before 
study completion. 
 
10.2 
      REPORTING AND PUBLICATION 
 
All data generated in this study are the property of the Sponsor. An integrated clinical and statistical 
report will be prepared at the completion of the study. 
 
Publication of the results by the Investigator will be subject to mutual agreement between the Investigator 
and the Sponsor and will follow the Sponsor’ Standard Operating Procedure on publications. 
 
11.0 
INVESTIGATOR OBLIGATIONS 
 
11.1 
DOCUMENTATION 
 
The Investigator must provide the following to the Sponsor before the start of the study: 
 
1. A completed and signed Form FDA 1572. If, during the course of the study, any changes are 
made that are not reflected on Form FDA 1572, a new Form FDA 1572 must be completed and 
returned to the Sponsor for submission to the FDA 

                                                                                                                                             
1 
 
2. A fully executed contract. 
 
3. The curricula vitae for the Investigator and all sub-investigators listed on Form FDA 1572, 
including a copy of each physician‘s license. 
 
4. A copy of the original IRB approval for conducting the study. If the study is ongoing, renewals 
must be submitted at yearly intervals. All subsequent modifications must be submitted and 
approved by the IRB, as stated in Section 5.1. 
 
5. A copy of the IRB-approved ICF 
 
6. A copy of the HIPAA authorization form, or other local privacy applicable forms 
 
7. A list of the IRB members or the US Department of Health and Human Services general 
assurance number 
 
8. A copy of the laboratory certifications and reference ranges 
 
9. The Investigator‘s Statement page in this protocol, signed and dated by the Investigator 
 
10. Financial disclosure agreement, completed and signed by the Investigator and all sub-
investigators listed on Form FDA 1572. The Investigator and all sub-investigators will provide 
an updated financial disclosure agreement to the Sponsor 1 year after the completion of the 
study. 
 
11.2 
PERFORMANCE 
 
The Investigator must demonstrate reasonable efforts to obtain qualified patients for the study. 
 
11.3 
USE OF INVESTIGATIONAL MATERIALS 
 
The Investigator will acknowledge that the supplies (ActiWatch, Computers and Scales) are 
investigational and as such must be used strictly in accordance with the protocol and only under the 
supervision of the Investigator or sub-investigators. The supplies must be stored in a secured place and 
must be locked. The Investigator must maintain adequate records documenting the receipt of all study 
supplies. The Sponsor will supply forms on which to record the date of the supplies was received and all 
unused supplies must be returned to the Sponsor. 
 
11.4 
               CASE REPORT FORMS 
 
All patient data relating to the study will be recorded on eCRFs to be provided by the Sponsor through 
the MDC (Manual data capture) system. The Investigator is responsible for verifying that all data entries 
in the eCRFs are accurate and correct by signing the completed eCRF casebook submitted to the 
Sponsor. The Investigator must maintain and retain accurate documentation that supports the information 
entered into the MDC system for source document verification and possible regulatory inspection. 
 
11.5 
RETENTION AND REVIEW OF RECORDS 
 
Records and documents pertaining to the conduct of this study, including eCRFs, source documents, 
consent forms, regulatory documents, calibration logs, or reports and medication inventory records in all 
formats (including, but not limited to, written, electronic, magnetic, and optical records, and scans, x-

2 
rays, and ECGs) must be retained by the Investigator for a period of at least 15 years after study 
completion unless local regulations or institutional policies require a longer retention period or otherwise 
notified in writing by the Sponsor. 
 
No study records shall be destroyed without notifying the Sponsor and providing the Sponsor the 
opportunity to arrange long-term storage for such study records or authorizing in writing the 
destruction of records after the required retention period.  The Investigator must permit access to 
any documentation relating to the study upon request of the Sponsor or applicable regulatory 
authorities. If the Investigator for the study retires, relocates, or for other reasons withdraws from 
the responsibility of keeping the study records, custody must be transferred to a suitable alternate 
custodian employee of the institution or to a suitably qualified and responsible third party. The 
Sponsor must be notified in writing of the name and address of the new custodian in advance of the 
transfer. 
 
11.6 
PATIENT CONFIDENTIALITY 
 
All patient records will only be identified by initials and “Participant Number” (PN).  Patient’s names are 
not to be transmitted to the Sponsor. The Investigator will keep a master patient list on which the 
“Participant Number” (PN) and the full name, address, and telephone number. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                             
1 
12.0 
           INVESTIGATOR’S STATEMENT 
 
 
I agree to conduct the study in accordance with this protocol (PSPC-17-01, Dated:         ) and 
with all applicable government regulations and good clinical practice guidance. 
 
_______________________________________ 
_____/_____/______ 
 
Investigator‘s Signature 
Date 
 
_______________________________________ 
 
Investigator‘s Name 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
13.0 
                                 APPENDICES 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                             
1 
APPENDIX I 
     ELEMENTS OF INFORMED CONSENT 
   
Procedures will comply with 21 CFR, Parts 50 and 312. Signed informed consent will be 
obtained for each patient participating in a clinical research study. This consent must include the 
following items: 
 
1. A statement that the study involves research and an explanation of the purposes of the 
research; a description of the procedures to be followed and the identification of any 
procedures that are experimental; and the expected duration of the patient‘s participation 
 
2. A description of any reasonably foreseeable risks or discomforts to the patient 
 
3. A description of any benefits to the patient or to others that may reasonably be expected 
from the research. If the patient is to be paid for participating in the study, the consent 
form must state the amount that he/she will receive and the schedule of payment (to 
ensure neither coercion nor undue influence). 
 
4. A disclosure of appropriate alternative procedures or courses of treatment, if any, that 
might be advantageous to the patient 
 
5. A statement describing the extent, if any, to which confidentiality of records identifying 
the patient will be maintained and noting the possibility that the FDA, the Sponsor, the 
IRB, or an authorized contract research organization may inspect the records 
 
6. For research involving more than minimal risk, an explanation of whether any medical 
treatment is available if injury occurs and, if so, what it consists of or where further 
information may be obtained 
 
7. An explanation of whom to contact, including the relevant telephone number, for answers to 
pertinent questions about the research and the research patient‘s rights and whom to contact 
in the event of a research-related injury to the patient. (Note: In some cases, it may be 
necessary to identify a person other than the Investigator as the contact. The guidance of the 
IRB may be required.) 
 
8. A statement that participation is voluntary, that refusal to participate will involve no 
penalty or loss of benefits to which the patient is otherwise entitled, and that the patient 
may discontinue participation at any time without penalty or loss of benefits to which the 
patient is otherwise entitled 
 
9. A statement that the particular treatment or procedures may involve risks to the patient 
(or to the embryo or fetus if the patient is, or may become, pregnant) that are at present 
unforeseeable 
 
10. The expected circumstances for which the patient‘s participation may be terminated by 
the Investigator without regard to the patient‘s consent 
 
11. Any additional costs to the patient that may result from participation in the research 

2 
 
12. The consequences of a patient‘s decision to withdraw from the research and 
procedures for an orderly termination of the patient‘s participation 
 
13. A statement that significant new findings developed during the course of the research that 
may relate to the patient‘s willingness to continue participation will be provided to the 
patient 
 
14. The approximate number of patients involved in the study 
 
15. A statement of permission, providing consent for the patient to participate (eg, —I 
agree to participate . . .“) 
 
16. A place for the patient‘s signature and date of signing of the ICF 
 
A statement indicating that information about this study has been, or will be, entered into a 
databank that is publicly accessible at www.ClinicalTrials.gov. 
 
      A copy of the signed consent form must be given to the patient. 

                                                                                                                                             
1 
APPENDIX II 
             CONTACT INFORMATION 
 
Contact information for the Sponsor personnel is maintained in the Study Reference 
Manual. 

2 
APPENDIX III 
       CONCOMITANT MEDICATIONS 
 
 Medications which are considered necessary for the patient's welfare may be given at 
the discretion of the Investigator. If the permissibility of a specific 
medication/treatment is in question, please contact the Medical Director.  
 
Concomitant Medications  
Date of Visit:__/__/___  Patient Initials:_____ Subject Number:________ 
 
Note: if yes is not checked, patient is not taking listed medication/nutrient 
 
 
Nutrient 
Consumed 2 weeks 
prior to 
randomization? 
Date Consumed 
CYP3A4 Modulators 
(e.g.  grapefruit juice, 
St John’s Wort) 
 
 
 
Common Concomitant Medications (these are examples, not a complete list) 
 
Drug 
Currently 
Taking? 
Dosage (if yes) 
Indication 
Barbiturates (ex. 
Phenobarbital) 
 
 
 
Carbamazepine (ex. 
Tegretol) 
 
 
 
Erythromycin (ex. 
Erythrocin, EES) 
 
 
 
Valproic acid (ex. 
Depakote, Valparin) 
 
 
 
Oxcarbazepine (ex. 
Trileptal) 
 
 
 
 
Other Concomitant Medications (these are examples of CYP3A4 inhibitors/inducers) 
 
Drug 
Currently 
Taking? 
Dosage (if 
yes) 
Indication 
Amiodarone (ex. Cordarone, Pacerone) 
 
 
 
Amprenavir (ex. Agenerase)  
 
 
 
Aprepitant (ex. Cordarone) 
 
 
 
Atazanavir (ex. Reyataz) 
 
 
 
Buspirone 
 
 
 
Chloramphenicol (ex. Chloromycetin, 
Chlorsig) 
 
 
 
Cimetidine (ex. Tagamet) 
 
 
 
Ciprofloxacin (ex. Ciloxan, cipro) 
 
 
 

                                                                                                                                             
1 
Clarithromycin (ex Crixan, Biaxin) 
 
 
 
Clozapine 
 
 
 
Cyclosporine (Neoral, Sandimmune) 
 
 
 
Delavirdine (ex Rescriptor) 
 
 
 
Diethyl-Dithiocarbamate 
 
 
 
Diltiazem (ex Cardizem, Dilacorxr) 
 
 
 
Desmopressin (DDAVP) 
 
 
 
Dexamethasone (ex decadron) 
 
 
 
Efavirenz (ex. Sustiva) 
 
 
 
Fluconazole (ex. Diflucan) 
 
 
 
Fluvoxamine (ex Luvox) 
 
 
 
Fosamprenavir (ex Lexiva) 
 
 
 
Gestodene 
 
 
 
Glucocorticoids (ex Cortisol) chronic use 
 
 
 
Imatinib (ex Gleevec) 
 
 
 
Indinavir (ex. Crixivan) 
 
 
 
Itraconazole 
 
 
 
Ketoconazole (ex Feoris, Nizoral) 
 
 
 
Lithium 
 
 
 
Mibefradil (ex Posicor) 
 
 
 
Modafinil (ex 
Provigil, Alertec, Modavigil) 
 
 
 
Nefazodone (Serzone, Nefadar) 
 
 
 
Nelfinavir (ex Viracept) 
 
 
 
Norfloxacin (ex Noroxin) 
 
 
 
Nevirapine (ex Viramune) 
 
 
 
Oxytocin 
 
 
 
Phenytoin (ex. Dilantin) 
 
 
 
Pioglitazone (ex Actos, Glustin) 
 
 
 
Pregabalin 
 
 
 
Ritonavir (ex Norvir) 
 
 
 
Rifabutin (ex Mycobutin) 
 
 
 
Rifampin (ex Rifadin) 
 
 
 
Saquinavir (ex Invirase) 
 
 
 
St John’s Wort 
 
 
 
Telithromycin (ex Ketek) 
 
 
 
Troleandomycin (ex Triocetin) 
 
 
 
Troglitazone (ex Rezulin, Resulin or 
Romozin) 
 
 
 
Verapamil (ex Isoptin, Verelan, 
Calan, Bosoptin) 
 
 
 
Voriconazole (ex Vfend) 
 
 
 
 

2 
 
APPENDIX IV                    Beck Depression Inventory (BDI) 
 
On this questionnaire are groups of statements.  Please read each group of statements carefully.  
Then pick the one statement in each group which best describes the way you have been feelings 
the PAST WEEK, INCLUDING TODAY.  Circle the number beside the statement you picked.  
Be sure to read all the statements in each group before making your choice. 
 
This depression inventory can be self-scored.  The scoring scale is at the end of the 
questionnaire. 
 
Sadness 
0.  I do not feel sad. 
1.  I feel sad much of the time. 
2.  I am sad all of the time. 
3.  I am so sad or unhappy that I can’t stand it. 
 
Pessimism 
0.  I am not discouraged about my future. 
1.  I feel more discouraged about my future than I used to be. 
2.  I do not expect things to work out for me. 
3.  I feel my future is hopeless and will only get worse. 
 
Past Failure 
0.  I do not feel like a failure. 
1.  I have failed more than I should have. 
2.  As I look back I see a lot of failures. 
3.  I feel I am a total failure as a person. 
 
Loss of Pleasure 
0.  I get as much pleasure as I ever did from the things I enjoy. 
1.  I don’t enjoy things as much as I used to. 
2.  I get very little pleasure from the things I used to enjoy. 
3.  I can’t get any pleasure from the things I used to enjoy. 
 
Guilty Feelings 
0.  I don’t feel particularly guilty. 
1.  I feel guilty over many things I have done or should have done. 
2.  I feel guilty most of the time. 
3.  I feel guilty all of the time. 
 
Punishment Feelings 
0.  I don’t feel like I am being punished. 
1.  I feel I may be punished. 
2.  I expect to be punished. 
3.  I feel I am being punished. 

                                                                                                                                             
1 
 
Self-Dislike 
0.  I feel the same about myself as ever. 
1.  I have lost confidence in myself. 
2.  I am disappointed in myself. 
3.  I dislike myself. 
 
Self-Criticalness 
0.  I don’t criticize or blame myself more than usual. 
1.  I am more critical of myself than I used to be. 
2.  I criticize myself for all of my faults. 
3.  I blame myself for everything bad that happens. 
 
Suicidal Thoughts or Wishes 
0.  I don’t have any thoughts of killing myself. 
1.  I have thoughts of killing myself, but I would not carry them out. 
2.  I would like to kill myself. 
3.  I would kill myself if I had the chance. 
 
Crying 
0.  I don’t cry anymore than I used to. 
1.  I cry more than I used to. 
2.  I cry over every little thing. 
3.  I feel like crying, but I can’t. 
 
Agitation 
0.  I am no more restless or wound up than usual. 
1.  I feel more restless or wound up than usual. 
2.  I am so restless or agitated that it’s hard to stay still. 
3.  I am so restless or agitated that I have to keep moving or doing something. 
 
Loss of Interest 
0.  I have not lost interest in other people or activities. 
1.  I am less interested in other people or things than before. 
2.  I have lost most of my interest in other people or things. 
3.  It’s hard to get interested in anything. 
 
Indecisiveness 
0.  I make decisions about as well as ever. 
1.  I find it is more difficult to make decisions than usual. 
2.  I have much greater difficulty in making decisions than I used to. 
3.  I have trouble making any decisions. 
 
 
 
 

2 
 
Worthlessness 
0.  I do not feel I am worthless.  
1.  I don’t consider myself as worthwhile and useful as I used to. 
2.  I feel more worthless as compared to other people. 
3.  I feel utterly worthless. 
 
Loss of Energy 
0.  I have as much energy as ever. 
1.  I have less energy than I used to have. 
2.  I don’t have enough energy to do very much. 
3.  I don’t have enough energy to do anything. 
 
Changes in Sleeping Pattern 
0.  I have not experienced any change in my sleeping pattern. 
1.  I sleep somewhat less than usual –or– I sleep a lot more than usual. 
2.  I sleep a lot less than usual –or– I sleep a lot more than usual. 
3.  I sleep most of the day –or– I wake up 1-2 hours early and can’t get back to sleep. 
 
Irritability 
0.  I am no more irritable than usual. 
1.  I am more irritable than usual. 
2.  I am much more irritable than usual. 
3.  I am irritable all the time. 
 
Changes in Appetite 
0.  I have not experienced any change in my appetite. 
1.  My appetite is somewhat less than usual –or– My appetite is somewhat greater   
      than usual. 
2.   My appetite is much less than usual –or– My appetite is much great than usual. 
3.  I have no appetite at all –or– I crave food all the time. 
 
Concentration Difficulty 
0.  I can concentrate as well as ever. 
 
1.  I can’t concentrate as well as usual. 
2.  It’s hard to keep my mind on anything for very long. 
3.  I find I can’t concentrate on anything. 
 
Tiredness of Fatigue 
0.  I am no more tired or fatigued than usual. 
1.  I get more tired or fatigued more easily than usual. 
2.  I am too tired or fatigued to do a lot of the things I used to do. 
3.  I am too tired or fatigued to do most of the things I used to do. 
 
 
 

                                                                                                                                             
1 
 
 
Loss of Interest in Sex 
0.  I have not noticed any recent change in my interest in sex. 
1.  I am less interested in sex than I used to be. 
2.  I am much less interested in sex now. 
3.  I have lost interest in sex completely. 
 
 
INTERPRETING THE BECK DEPRESSION INVENTORY 
 
Now that you have completed the questionnaire, add up the score for each of the twenty-one 
questions by counting the number to the right of each question you marked.  The highest possible 
total for the whole test would be sixty-three.  This would mean you circled number three on all 
twenty-one questions.  Since the lowest possible score for each question is zero, the lowest 
possible score for the test would be zero.  This would mean that you circled zero on each 
question.  You can evaluate your depression according to the Table below. 
 
 
Total  Score ________________________ Levels of Depression 
1–10______________________________ These ups and downs are considered normal 
11–16______________________________Mild mood disturbance 
17–20_____________________________ Borderline clinical depression 
21–30_____________________________ Moderate depression 
31–40_____________________________ Severe depression 
Over 40____________________________ Extreme depression 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
APPENDIX V                      Beck Anxiety Inventory 
 
Below is a list of common symptoms of anxiety.  Please carefully read each item in the list.  Indicate how much you 
have been bothered by that symptom during the past month, including today, by circling the number in the 
corresponding space in the column next to each symptom. 
 
 
   Not At All 
Mildly, but it didn’t 
bother me much. 
Moderately – it 
wasn’t pleasant at 
times 
Severely – it 
bothered me a lot 
Numbness or tingling 
0 
1 
2 
3 
Feeling hot 
0 
1 
2 
3 
Wobbliness in legs 
0 
1 
2 
3 
Unable to relax 
0 
1 
2 
3 
Fear of the worst 
happening 
0 
1 
2 
3 
Dizzy or lightheaded 
0 
1 
2 
3 
Heart pounding/racing 
0 
1 
2 
3 
Unsteady 
0 
1 
2 
3 
Terrified or afraid 
0 
1 
2 
3 
Nervous 
0 
1 
2 
3 
Feeling of choking 
0 
1 
2 
3 
Hands trembling 
0 
1 
2 
3 
Shaky / unsteady 
0 
1 
2 
3 
Fear of losing control 
0 
1 
2 
3 
Difficulty in breathing 
0 
1 
2 
3 
Fear of dying 
0 
1 
2 
3 
Scared 
0 
1 
2 
3 
Indigestion 
0 
1 
2 
3 
Faint/ lightheaded 
0 
1 
2 
3 
Face flushed 
0 
1 
2 
3 
Hot/cold sweats 
0 
1 
2 
3 
Column Sum 
 
 
 
 
 
Scoring –  Sum each column.  Then sum the column totals to achieve a grand score.  Write that score here -
___________. 
Interpretation 
 
A grand sum between 0 – 21 indicates very low anxiety.  That is usually a good thing.  However, it is possible that 
you might be unrealistic in your assessment which would be denial or that you have learned to “mask” the 
symptoms commonly associated with anxiety.  Too little anxiety could indicate that you are detached from yourself, 
others, or your environment. 
 
A grand sum between 22 – 35 indicates moderate anxiety.  Your body is trying to tell you something.  Look for 
patterns as to when and why you experience the symptoms described above.  For example, if it occurs prior to public 
speaking and your job requires a lot of presentations you may want to find ways to calm yourself before speaking or 
let others do some of the presentations.  You may have some conflict issues that need to be resolved.  Clearly, it is 
not “panic” time but you want to find ways to manage the stress you feel. 
 
A grand sum that exceeds 36 is a potential cause for concern.  Again, look for patterns or times when you tend to 
feel the symptoms you have circled.  Persistent and high anxiety is not a sign of personal weakness or failure.  It is, 
however, something that needs to be proactively treated or there could be significant impacts to you mentally and 
physically.  You may want to consult a physician or counselor if the feelings persist. 
 

                                                                                                                                             
1 
 
 
 
APPENDIX VI                          Goal Motivation Scale 
The following three statements are followed by a visual scale in which  
0 = “Strongly Disagree” and 9 = “Strongly Agree.” Place a mark on the scale that you feel best represents how much 
you disagree or agree with the statement.  
 
1.  I put a lot of effort toward achieving my goals in life.  
 
0 
 9 
2.  I am committed to achieving my goals in life.  
 
0 
 9 
3.  I am willing to work toward achieving my goals in life.  
 
0 
 9 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
 
 
APPENDIX VII                      Goal Motivation Scale - Insomnia 
The following three statements are followed by a visual scale in which  
0 = “Strongly Disagree” and 9 = “Strongly Agree.” Place a mark on the scale that you feel best represents how much 
you disagree or agree with the statement.  
 
1.  I put a lot of effort toward resolving my insomnia.  
 
0 
 9 
2.  I am committed to resolving my insomnia.  
 
0 
 9 
3.  I am willing to work toward resolving my insomnia.  
 
0 
 9 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                             
1 
 
 
 
APPENDIX VIII                      INSOMNIA SEBVERITY INDEX 
 
 
 
 
 

2 
 
 
 
APPENDIX IX             SELF REPORT SLEEP MEASURES 
 
Participant’s Name: __________________________ 
Date: _____________ 
 
We want your assessment of specific aspects of your experience with sleep and 
insomnia during the past week.  Be as accurate as you can. 
 
I. Please circle the number/words that best describe how satisfied or dissatisfied 
you have been about your ability to get to sleep at bedtime during the past week. 
 
-3            
 -2            
1-           
  0             
+1            
 +2             
+3 
Very              Somewhat          Slightly        Neither Satisfied         Slightly           Somewhat            Very 
Dissatisfied   Dissatisfied      Dissatisfied    Nor Dissatisfied 
Satisfied          Satisfied            Satisfied  
                                               
II. Circle the number/words that best describe how satisfied or dissatisfied you 
are about your frequency of awakenings after having initiated sleep during the 
past week. 
 
-3            
 -2            
1-           
  0             
+1            
 +2             
+3 
Very              Somewhat          Slightly        Neither Satisfied         Slightly           Somewhat            Very 
Dissatisfied   Dissatisfied      Dissatisfied    Nor Dissatisfied 
Satisfied          Satisfied            Satisfied  
 
III. Circle the number/words that best describe how satisfied or dissatisfied you 
are about your ability to return to sleep after awakenings during the night over 
past week. 
 
-3            
 -2            
1-           
  0             
+1            
 +2             
+3 
Very              Somewhat          Slightly        Neither Satisfied         Slightly           Somewhat            Very 
Dissatisfied   Dissatisfied      Dissatisfied    Nor Dissatisfied 
Satisfied          Satisfied            Satisfied  
 
IV. Please circle the number and words that best describe how satisfied or 
dissatisfied you are about your average quantity of sleep during this past week. 
 
-3            
 -2            
1-           
  0             
+1            
 +2             
+3 
Very              Somewhat          Slightly        Neither Satisfied         Slightly           Somewhat            Very 
Dissatisfied   Dissatisfied      Dissatisfied    Nor Dissatisfied 
Satisfied          Satisfied            Satisfied  
 
V. Which number/words best describe how satisfied or dissatisfied you are 
about your overall quality of sleep during the past week? 
 
-3            
 -2            
1-           
  0             
+1            
 +2             
+3 
Very              Somewhat          Slightly        Neither Satisfied         Slightly           Somewhat            Very 
Dissatisfied   Dissatisfied      Dissatisfied    Nor Dissatisfied 
Satisfied          Satisfied            Satisfied  

                                                                                                                                             
1 
 
VI. On a scale of 1 to 10, where 0 is no distress or neutral and 10 is the highest 
level of distress you can imagine, how distressing has your sleep difficulty been 
during this past week? 
 
_____ on zero to ten (0-10) scale. 
 
VII. “Social impairment” refers to how much your sleep difficulty negatively 
impacts your social functioning.  How much does it impede or negatively impact 
your social functioning?  If zero equals “Not at all” or no social impairment and 
10 is the highest level of social impairment you can imagine, what is your best 
estimate of the level of social impairment due to your sleep difficulty during the 
last month? 
 
_____ on zero to ten (0-10) scale. 
 
If the participant is employed, 
VIII. “Occupational impairment” refers to how much your sleep difficulty 
negatively impacts your occupational functioning, your ability to perform your 
job.  How much does it impede or negatively impact your occupational 
functioning?  If zero equals “Not at all” or no occupational impairment and 10 
is the highest level of occupational impairment you can imagine, what is your 
best estimate of the level of occupational impairment due to your sleep difficulty 
during the last month? 
 
_____ on zero to ten (0-10) scale. 
 
If the participant is a full time or part time student, 
IX. “Academic impairment” refers to how much your sleep difficulty negatively 
impacts your academic functioning.  How much does it impede your academic 
functioning?  If zero equals “Not at all” or no academic impairment and 10 is 
the highest level of academic impairment you can imagine, what is your best 
estimate of the level of academic impairment due to your sleep difficulty during 
the last month? 
 
_____ on zero to ten (0-10) scale. 
 
 
 
 
 
 

2 
 
 
APPENDIX X  Clinical Global Impression – Global Improvement (CGI –I) Scale  
  
Patient Name:                                                                                    Date:  
  
Clinician Name:  
 
 
Rate total improvement whether or not, in your clinical judgment, it is due entirely to drug 
treatment.  
   
Compared to his/her condition at baseline, how much has he/she changed?  
  
 □  0 = Not assessed    
 □  1 = Very much improved    
 □  2 = Much improved   
 □  3 = Minimally improved    
 □  4 = No change    
 □  5 = Minimally worse    
 □  6 = Much worse    
 □  7 = Very much worse 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                                                                                                                             
1 
 
 
APPENDIX XI  
CLINICAL GLOBAL IMPRESSIONS-SEVERITY  
                                                      SEVERITY OF ILLNESS 
 
Considering your total clinical experience with this population, how mentally ill is the patient 
at this time? (Check one) 
 
1 
Normal, not at all ill 
 
2 
Borderline ill 
 
3 
Mildly ill 
 
4 
Moderately ill 
 
5 
Markedly ill 
 
6 
Severely ill 
 
7 
Among the most extremely ill patients 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
APPENDIX XII   Quality of Life Enjoyment and Satisfaction Questionnaire – Short 
Form (Q-LES-Q-SF) 
 
Name:______________________________________  Date:_________________  
 
 
 
 
 
 

                                                                                                                                             
1 
 
 
 
 
 
 

2 
APPENDIX XIII 
COLUMBIA-SUICIDE SEVERITY RATING SCALE 
 
BASELINE/SCREENING 
 

                                                                                                                                             
1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

2 
 
APPENDIX XIV 
COLUMBIA SUICIDE SEVERITY RATING SCALE - 
 
SINCE LAST VISIT 
 
 
COLUM BI A-SUICIDE SEVERITY 
 
RATING SCALE 
(C-SSRS) 
Since Last Visit 
Version 1/14/09 
 
Posner, K.; Brent, D.; Lucas, C.; Gould, M.; Stanley, B.; Brown, G.; Fisher, P.; 
 
Zelazny, J.; Burke, A.; Oquendo, M.; Mann, J. 
 
Disclaimer: 
 
This scale is intended for use by trained clinicians. The questions contained in the Columbia -Suicide 
Severity Rating Scale are suggested probes. Ultimately, the determination of the presence of suicidality 
depends on clinical judgment. 
 
 
Definitions of behavioral suicidal events in this scale are based on those used in The Columbia Suicide 
History Form, developed by John Mann, MD and Maria Oquendo, MD, Conte Center for the 
Neuroscience of Mental Disorders (CCNMD), New York State Psychiatric Institute, 1051 Riverside 
Drive, New York, NY 10032. (Oquendo M. A., Halberstam B. & Mann J. J., Risk factors for suicidal 
behavior: utility and limitations of research instruments. In M.B. First [Ed.] Standardized Evaluation in 
Clinical Practice, pp. 103 -130, 2003.) 
 
For reprints of the C-SSRS contact Kelly Posner, Ph.D., New York State Psychiatric Institute, 1051 
Riverside Drive, New York, New York, 10032; inquiries and training requirements contact 
posnerk@childpsych.columbia.edu 
 
© 2008 The Research Foundation for Mental Hygiene, Inc. 
 
 
SUICIDAL IDEATION 
 
Ask questions 1 and 2. If both are negative, proceed to —Suicidal Behavior“ section. If the 
Since 
answer to question 2 is —yes“ , ask questions 3, 4, and 5. If the answer to question 1 and/or 2 is 
—yes“ , complete —Intensity of Ideation“ section below. 
Last Visit 
1. Wish to be Dead 
Subject endorses thoughts about a wish to be dead or not alive anymore, or wish to fall asleep and not wake up. 
Yes No 
Have you wished you were dead or wished you could go to sleep and not wake up? 
̉̉ 
If yes, describe: 
2. Non-Specific Active Suicidal Thoughts 
General, non-specific thoughts of wanting to end one‘s life/commit suicide (e.g., —I‘ve thought about killing myself“ ) 
Yes No 
without thoughts of ways to kill oneself/associated methods, intent, or plan during the assessment period. 
̉̉ 

                                                                                                                                             
1 
Have you actually had any thoughts of killing yourself? 
If yes, describe: 
 
3. Active Suicidal Ideation with Any Methods(Not Plan) without Intent to Act 
Subject endorses thoughts of suicide and has thought of at least one method during the assessment period. This is 
different than a specific plan with time, place, or method details worked out (e.g., thought of method to kill self but not a 
Yes No 
specific plan). Includes person who would say, —I thought about taking an overdose but I never made a specific plan as 
̉̉ 
to when, where, or how I would actually do it…and I would never go through with it.“ 
Have you been thinking about how you might do this? 
If yes, describe: 
4. Active Suicidal Ideation with Some Intent to Act, without Specific Plan 
Active suicidal thoughts of killing oneself and subject reports having some intent to act on such thoughts, as opposed to 
Yes No 
—I have the thoughts but I definitely will not do anything about them.“ 
̉ 
Have you had these thoughts and had some intention of acting on them? 
If yes, describe: 
5. Active Suicidal Ideation with Specific Plan and Intent 
Yes No 
Thoughts of killing oneself with details of plan fully or partially worked out and subject has some intent to carry it out. 
Have you started to work out or worked out the details of how to kill yourself? Do you intend to carry out this plan? 
̉̉ 
If yes, describe: 
INTENSITY OF IDEATION 
The following features should be rated with respect to the most severe type of ideation (i.e., 1-5 from 
Most 
above, with 1 being the least severe and 5 being the most severe). 
Most Severe Ideation: ______________________________________________________ 
Severe 
Type # (1-5) Description of Ideation 
Frequency 
How many times have you had these thoughts? 
____ 
(1) Less than once a week (2) Once a week (3) 2-5 times in week (4) Daily or almost daily (5) Many times each day 
Duration 
When you have the thoughts, how long do they last? 
____ 
(1) Fleeting - few seconds or minutes 
(4) 4-8 hours/most of day 
(2) Less than 1 hour/some of the time 
(5) More than 8 hours/persistent or continuous 
(3) 1-4 hours/a lot of time 
Controllability 
Could/can you stop thinking about killing yourself or wanting to die if you want to? 
____ 
(1) Easily able to control thoughts 
(4) Can control thoughts with a lot of difficulty 
(2) Can control thoughts with little difficulty (5) Unable to control thoughts 
(3) Can control thoughts with some difficulty (0) Does not attempt to control thoughts 
Deterrents 
Are there things - anyone or anything (e.g., family, religion, pain of death) - that stopped you from 
wanting to die or acting on thoughts of committing suicide? 
____ 
(1) Deterrents definitely stopped you from attempting suicide   (4) Deterrents most likely did not stop you 
(2) Deterrents probably stopped you 
(5) Deterrents definitely did not stop you 
(3) Uncertain that deterrents stopped you 
(0) Does not apply 
 
Reasons for Ideation 
 
What sort of reasons did you have for thinking about wanting to die or killing yourself? Was it to end the pain 
or stop the way you were feeling (in other words, you couldn‘t go on living with this pain or how you were 
feeling) or wasit to get attention, revenge ,or a reaction from others? Or both? 
(1) Completely to get attention, revenge or a reaction from others (5) Completely to end or stop the pain (you 
____
(2) Mostly to get attention, revenge or a reaction from others living 
couldn‘t go on living with the pain or how 
(3) Equally to get attention, revenge or a reaction from others 
you were feeling) 
and to end/stop the pain 
(0) Does not apply 
 
(4) Mostly to end or stop the pain (you couldn‘t go on living 
with the pain or how you werefeeling). 

2 
 
 
 
 
 
SUICIDAL BEHAVIOR 
Since 
(Check all that apply, so long as these are separate events; must ask about all types) 
Last Visit 
Actual Attempt: 
Yes No 
A potentially self-injurious act committed with at least some wish to die, as a result of act. Behavior was in part thought 
of as method to kill oneself. Intent does not have to be 100%. If there is any intent/desire to die associated with the act, ̉̉ 
then it can be considered an actual suicide attempt. There does not have to be any injury or harm, just the potential for 
injury or harm. If person pulls trigger while gun is in mouth but gun is broken so no injury results, this is considered an 
attempt. 
Total # of 
Inferring Intent: Even if an individual denies intent/wish to die, it may be inferred clinically from the behavior or 
circumstances. For example, a highly lethal act that is clearly not an accident so no other intent but suicide can be 
Attempts 
inferred (e.g., gunshot to head, jumping from window of a high floor/story). Also, if someone denies intent to die, but 
______ 
they thought that what they did could be lethal, intent may be inferred. 
Have you made a suicide attempt? 
Have you done anything to harm yourself? 
Have you done anything dangerous where you could have died? 
What did you do? 
Did you______ as a way to end your life? 
Did you want to die (even a little) when you_____? 
Were you trying to end your life when you _____? 
Or did you think it was possible you could have died from_____? 
Or did you do it purely for other reasons / without ANY intention of killing yourself (like to relieve stress, 
feel better, get sympathy, or get something else to happen)? (Self-Injurious Behavior without suicidal intent) 
If yes, describe: 
Yes No 
Has subject engaged in Non-Suicidal Self-Injurious Behavior? 
̉̉ 
Interrupted Attempt: 
Yes No 
When the person is interrupted (by an outside circumstance) from starting the potentially self-injurious act (if not for 
that, actual attempt would have occurred). 
̉̉ 
Overdose: Person has pills in hand but is stopped from ingesting. Once they ingest any pills, this becomes an attempt 
rather than an interrupted attempt. Shooting: Person has gun pointed toward self, gun is taken away by someone else, or 
is somehow prevented from pulling trigger. Once they pull the trigger, even if the gun fails to fire, it is an attempt. 
Total # of 
Jumping: Person is poised to jump, is grabbed, and taken down from ledge. Hanging: Person has noose around neck but 
has not yet started to hang - is stopped from doing so. 
Interrupted 
Has there been a time when you started to do something to end your life but someone or something 
______ 
stopped you before you actually did anything? 
If yes, describe: 
Aborted Attempt: 
Yes No 
When person begins to take steps toward making a suicide attempt, but stops themselves before they actually have 
̉̉ 
engaged in any self-destructive behavior. Examples are similar to interrupted attempts, except that the individual stops 
him/herself, instead of being stopped by something else. 
Total # of 
Has there been a time when you started to do something to try to end your life but you stopped yourself 
Aborted 
before you actually did anything? 
______ 
If yes, describe: 
____ 
Preparatory Acts or Behavior: 
Acts or preparation towards imminently making a suicide attempt. This can include anything beyond a verbalization or 
thought, such as assembling a specific method (e.g., buying pills, purchasing a gun) or preparing for one‘s death by 
Yes No 
suicide (e.g., giving things away, writing a suicide note). 
Have you taken any steps towards making a suicide attempt or preparing to kill yourself (such as  
collecting pills, getting a gun, giving valuables away, or writing a suicide note)? 
If yes, describe: 
Suicidal Behavior: 
Yes No 
Suicidal behavior was present during the assessment period? 
̉ 

                                                                                                                                             
1 
 
 
 
Completed Suicide: 
Yes No 
̉̉ 
Most 
Answer for Actual Attempts Only 
Lethal 
Attempt 
Date: 
Actual Lethality/Medical Damage: 
0. No physical damage or very minor physical damage (e.g., surface scratches). 
1. Minor physical damage (e.g., lethargic speech; first-degree burns; mild bleeding; sprains). 
Enter Code 
2. Moderate physical damage; medical attention needed (e.g., conscious but sleepy, somewhat responsive; second-degree 
burns; bleeding of major vessel). 
3. Moderately severe physical damage; medical hospitalization and likely intensive care required (e.g., comatose with 
reflexes intact; third-degree burns less than 20% of body; extensive blood loss but can recover; major fractures). 
______ 
4. Severe physical damage; medical hospitalization with intensive care required (e.g., comatose without reflexes; third- 
degree burns over 20% of body; extensive blood loss with unstable vital signs; major damage to a vital area). 
5. Death 
Potential Lethality: Only Answer if Actual Lethality = 0 
Enter Code 
Likely lethality of actual attempt if no medical damage (the following examples, while having no actual medical 
damage, had potential for very serious lethality: put gun in mouth and pulled the trigger but gun fails to fire so no 
medical damage; laying on train tracks with oncoming train but pulled away before run over). 
0 = Behavior not likely to result in injury 
______ 
1 = Behavior likely to result in injury but not likely to cause death 
2 = Behavior likely to result in death despite available medical care 

2 
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