The Effect of Treatment of Obstructive Sleep Apnea on Diabetes Self Management and Glycemic Control
Phase: NA
Conditions: Type 2 Diabetes, Obstructive Sleep Apnea
Sponsor: Eileen R. Chasens

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Diabetes Sleep Treatment Trial (DSTT) - PRO16080062 
Protocol and Statistical Analysis Plan 
 
 
 

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A. SPECIFIC AIMS 
Obesity and sedentary lifestyle are associated with poor glucose control in persons with type 2 diabetes mellitus 
(T2DM) and resistance to behavioral interventions. While diabetes self-management education and counseling (DEC) 
has been improved and refined over the last 30 years, many persons with T2DM continue to have difficulty in achieving 
glycemic goals.1,2 Excessive daytime sleepiness, a frequent problem associated with obstructive sleep apnea (OSA), is a 
likely barrier to self-management of T2DM. The prevalence of OSA in persons withT2DM is notably greater than that for 
the general population, estimated to range from 40% to 97% depending on the degree of OSA severity and the age of the 
sample.3-6 In addition, results of previous studies suggest that OSA and T2DM not only co-exist but that sleep-related 
breathing disorders directly adversely affect glucose homeostasis. 7-14 The most effective medical treatment for OSA is 
CPAP which eliminates apneas and hypopneas during sleep, and results in improved self-reported daytime functioning.15-
18  Unfortunately, there is a notable gap in our understanding of the association between OSA and T2DM. The effect of 
CPAP treatment on glucose control remains unclear, with conflicting results possibly related to the previous studies 
having small sample sizes15-20 and not intervening in behavioral aspects of glycemic control. Therefore, the effect of OSA 
on behavioral aspects of diabetes self-management and the effect of CPAP treatment on diabetes education and 
counseling (DEC) remains unknown.  
 
Data from our preliminary studies in persons with T2DM suggest that excessive daytime sleepiness may be a barrier 
to effective diabetes self-management and that poor sleep is associated with suboptimal diabetes self-management.21,22 We 
recently completed the OSA, Sleepiness and Activity in Diabetes Management study (OSA-DM) a double blind, 
randomized, placebo-controlled pilot study (R21 HL 089522, PI, E. Chasens), that compared physical activity and 
glycemic control in adults with T2DM treated with active CPAP vs. those on sham-CPAP. Our preliminary data analysis 
suggests that CPAP treatment of OSA improves glycemic control and increases physical activity in persons with T2DM. 
Hence, we demonstrated the feasibility to recruit and retain subjects, a requirement for undertaking a larger study to test 
the efficacy of CPAP treatment in moderate-to-severe OSA in adults with T2DM. 
 
The underlying premise of the proposed study from this new investigator is that OSA hinders diabetes self-
management in adults with T2DM. The next step in understanding the effect of OSA on diabetes self-management is to 
determine the efficacy of CPAP treatment in improving diabetes outcomes in adults treated with CPAP compared to those 
on sham-CPAP. This proposal differs from the pilot/feasibility study in that we have a broader set of health outcomes that 
we are testing. We propose to enroll 210 adults with T2DM and moderate-to-severe OSA who have suboptimal diabetes 
self-management. We will conduct a 12-week double blind, randomized, placebo-controlled trial to determine if diabetes 
self-management outcomes and glycemic control are superior in subjects with OSA who are treated with CPAP and 
receive a DEC (CPAP + DEC) compared to control subjects (sham-CPAP + DEC). We will also explore the effect and 
robustness of treatment with CPAP (after 24-weeks) on glycemic control and factors associated with diabetes self-
management.  
 
Aim 1 (Primary): To determine if CPAP + DEC is superior to sham-CPAP + DEC for improving glycemic control.  H1: 
Subjects who receive CPAP + DEC will have improved glycemic control compared to subjects with sham-CPAP + DEC 
at 6 weeks and 12 weeks.   
 
Aim 2 (Secondary): To determine if CPAP + DEC is superior to sham-CPAP + DEC for improving diabetes self-
management outcomes. H2: Subjects who receive CPAP + DEC will have better diabetes self-management outcomes 
(retention of information taught during the DEC classes, improved self-management behaviors, diabetes monitoring 
activities, increased physical activity, and decreased diabetes-related distress compared to subjects with sham-CPAP + 
DEC at 6 weeks and 12 weeks. 
 
Aim 3: To explore adherence to CPAP (dose) and specific neuro-behavioral and physiological mechanisms (sleep quality, 
daytime sleepiness, mood, and vigilance that may mediate the effects of CPAP treatment on glycemic control and diabetes 
self-management outcomes (6 weeks and 12 weeks).   
 
Aim 4: To explore the association between the durability of treatment of OSA (i.e. adherence to CPAP) and sleep quality, 
daytime sleepiness, mood, diabetes self-management, and glycemic control after 24 weeks of active CPAP in the full 
sample. 
 
 
 

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B. PROTOCOL 
 
Design. We will use a 2-group, randomized controlled design with treatment cross-over. Adults with T2DM who have an 
AHI ≥ 10 and suboptimal diabetes management, defined as an A1C ≥ 6.5.0%, will be randomized to one of two 
conditions: CPAP + DEC vs. control group - sham-CPAP + DEC (see Figure 2). We will compare the primary outcomes 
between the two groups on 1) glycemic control and 2) diabetes self-management outcomes. After cross-over, we will pool 
subject’s 6 months data to evaluate 
robustness of treatment effects.  
Subjects and Recruitment 
We will recruit adults with T2DM who 
are at high risk for OSA and suboptimal 
diabetes management from UPMC 
diabetes and sleep clinics in the 
Pittsburgh area (Monroeville, Mount 
Lebanon, and Mt. Nebo) in addition to 
the Oakland site, the community, and the 
Veterans Administration Pittsburgh 
Healthcare System (VAPHS).  
 
At West Virginia University the 
following methods will be utilized to identify potential subjects: EPIC electronic medical record review, work with 
primary care providers in the Family Medicine, Medical Group Practice, and Medical Specialties clinics.  Brochures 
describing the trial will be made available in the outpatient settings. 
 
University of Pittsburgh will enhance strategies that were successful in the pilot/feasibility study by using resources from 
the Clinical & Translational Science Institute (CTSI), which has developed community partnerships to assist in the 
recruitment of minorities. We will also recruit from completed studies and research registries by having letters sent to 
former participants in those studies. The PI/Project Manager and their staff of studies or research registries will identify 
the participants who may be appropriate to receive the letter and will send the letters. We will utilize social media 
advertisements developed by TrialSpark to recruit for the study. Potential participants are screened on-line after they have 
indicated their consent, they will receive follow-up email messages informing them if they are eligible. Those persons 
who are potentially eligible will receive telephone phone calls to confirm their eligibility and to set up an appointment for 
the first assessment.  If individuals who receive the letter are interested in potentially participation in the DSTT study, 
they will be provided on the letter with DSTT contact information to obtain further study information. We will embed 
research staff in VAPHS and UPMC clinics to recruit subjects. We have initial contacts with the Hispanic Chamber of 
Commerce and the Latino Roundtable of Pittsburgh. We will directly recruit subjects by attending community events, 
speaking at public health events, placing flyers in the community, and through newspaper advertisements. We will expand 
recruitment by the co-investigators (Drs. Atwood, Korytkowski, and Strollo) speaking to medical providers in internal 
medicine, geriatric medicine, public health, women’s health, sleep, and diabetes clinics to discuss the study and encourage 
referral of potential subjects at the University of Pittsburgh and at the VAPHS. Drs. Rao and Atwood at the VAPHS will 
assist in identifying potential patients. We will develop pocket guides on the purpose of the study and inclusion/ exclusion 
criteria for medical providers.  
A brochure and flyer describing the study will be created for distribution; a “Dear Patient” letter will be generated for 
distribution to patients scheduled for diabetes and/or sleep clinic visits; a “Dear Colleague” letter will be generated and 
distributed to primary care, and women’s health physicians in the community; newspaper advertisements describing the 
study and seeking individuals who snore will be circulated in the local newspapers. Dr. Susan Redline will act as a 
consultant on recruitment.  
 
Eligibility criteria:.  
When the potential subjects have met the initial eligibility criteria, and before the sleep study is conducted, their PCP will 
be contacted by the study coordinator to inform him/her of the potential subject’s study participation and ask for their 
approval, if appropriate. 
 
The following criteria must be met for subjects to be randomized into the study:  
1) T2DM with suboptimal glucose control (A1C ≥ 6.5%),87,88 
2) AHI greater than ≥ 10 (ApneaLinkPlus®,  

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3) Age 18 years or older 
4) Willing to be randomized to CPAP or sham-CPAP.  
 
Exclusion criteria include: 
1.)   A1C > 11 
2.)   Gestational or type 1 DM 
3.)   Sleep duration < 4 hrs per day 
4.)  Change in diabetes medications during the previous 3 months 
5.) Acute medical or surgical conditions or hospitalization ≤ 3 months (e.g. angina, stroke, major surgery, major 
depression or serious psychiatric conditions) 
6.) Previous diagnosis of another sleep disorder, oxygen or bi-level PAP required 
7.) O2 sat. < 75% for > 25% of the ApneaLinkPlus sleep study  
8.) Cardiovascular events noted during overnight titration sleep study,  
9.)  Prior CPAP 
10.) Persons in household with CPAP  
11.) History of near-miss or auto accident during last 12 months  
12.) Employed in safety sensitive job (i.e. truck driver or airline pilot)  
13.) Non-ambulatory 
14.) Regular use of hypnotic or alerting (e.g. modafinil) medications  
Women: > 3 drinks a day and > 7 drinks per week 
16.) Claustrophobia to wearing mask  
17.) Unable to speak, read & write English  
18.) Pregnancy  
19. Request of PCP  
 
Exclusion criteria were determined to maintain subject safety and study integrity.  
 
Intervention and sham. 
Subjects in both arms of the study will be treated with the Respironics System One Auto CPAP System. This system 
contains a wireless modem (Respironics EncoreAnywhere™) that records adherence to CPAP nightly treatment and 
transmits the data to a password protected, web-based secure server. During the entire protocol, CPAP machines will be 
provided free of charge to the subjects; CPAP machines are being provided by the manufacturer (see Respironics, Inc. 
Letter of Support). A standardized procedure to ensure adherence will be utilized in both treatment arms. The 
EncoreAnywhere™ system will record data for the entire time CPAP is in use.  The Sleep Educator will upload 
participant adherence data from the EncoreAnywhere™ system on a regular (weekly) basis.  
A sham circuit, a modification of the design of Farré and co-workers89 manufactured by Respironics Inc., will create a 
CPAP placebo. This device was utilized by T. Weaver (CATNAP study) and by C. Kushida (APPLES study). This design 
places a hidden leak and a restrictor in the connector (Respironics, Inc WhisperSwivel®) between the mask and CPAP 
tubing that allows air to escape and to prevent the rebreathing of carbon dioxide. The pressure will be set to 0.5-1 cm H2O 
at the mask to generate sufficient airflow to convince the CPAP naïve subject that they are receiving treatment, however; 
the pressure is insufficient to hold open the pharynx. The airflow generates a similar degree of blower noise from both 
circuits, providing CPAP naïve subjects with audible and tactile cues that do not differ between sham and active-CPAP 
and thus maintains blinding. The only difference between the two circuits is the mask pressure, which is the desired 
variable to be blinded. Data demonstrate that the sham-CPAP does not deliver therapeutic pressure nor produce clinically 
meaningful alterations in pre-treatment AHI, the nadir of oxygen desaturation, arousal index, and sleep efficiency.90,91 
This design was used successfully by our research team in the pilot/feasibility study with subjects remaining blinded (p = 
.67) to the group assignment.  
Length of the intervention. The duration of the blinded intervention with sham comparison is 12 wks. This is based on 
previous studies in OSA patients demonstrating that improvements of objective sleepiness plateaus after 2 wks of 
treatment,94 results that are supported by several clinical trials that found significant improvement after 4 wks of CPAP 
treatment in subjective sleepiness,44-47 objective sleepiness,45,47 neuro-behavior outcomes,44 mood,45 and functional 
status.45,47 After the completion of the intervention, we will provide CPAP treatment to those subjects who were initially 
15.) Excessive consumption of alcohol.  
Men: > 4 drinks a day and more than 14 drinks per week 

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randomized to sham-CPAP. We will follow all subjects for a total of 24 weeks of therapeutic CPAP treatment to 
evaluation durability of adherence to CPAP, glycemic control, and behavioral outcomes.   
CPAP Titration Study/Sham-CPAP Titration. The nighttime CPAP titration PSG will be performed to determine the 
optimal level of CPAP needed to eliminate the subject’s apnea. The CPAP titration PSG will be performed using standard 
techniques,92 with effective CPAP level defined as an AHI <5/hr with the minimum effective pressure for each subject. 
Patients randomized to the sham-CPAP arm will have titration studies that are performed identically to the CPAP titration 
except the standard CPAP connection will have a sham-CPAP restrictor piece added, the modified expiratory valve will 
be attached and pressure at the nose mask will be < 1 cm H2O. The WhisperSwivel® connectors (sham and regular 
connectors) will be coded for the active CPAP intervention or the sham-CPAP group. A trained research Registered 
Polysomnographic Technologist at will choose the appropriate connector and record the number and the group 
(CPAP/sham-CPAP) in a secure file; this person is unblinded. The sham CPAP blower will be set at a pre-set level (this 
pressure is not transmitted to the subject, but determines the blower sound). The level of pressure for the blower of each 
sham CPAP participant will be displayed to participants as a “10 cm of H2O”. 
 
Setting.  
The N-CTRC, located at Western Psychiatric Institute and Clinic (WPIC), will be the site for all sleep studies (see letter of 
support Dr. Daniel Buysse) for University of Pittsburgh recruited. The setting for all assessments will be the VAPHS for 
subjects recruited there. . Montefiore Hospital CTRC (MUH-CTRC) will be the site for all University of Pittsburgh 
recruited participants.  
 
West Virginia University:  Subjects will be consented and undergo study procedures at the WVU Medicine outpatient 
clinics (Sleep Evaluation Center, Medical Group Practice, Family Medicine, and Medical Specialties clinics), and the 
Clinical Trials Research Unit. 
  
Study Measures. (See Appendix for copies of instruments). We selected the self-report and physiological measures to 
reflect the key behavioral domains that are adversely affected by OSA and EDS as documented by numerous published 
studies. They provide a comprehensive assessment of treatment response and the basis for secondary analyses and 
hypothesis generation. The tests are organized to reduce subject burden. Data from the pilot study indicate that the clinical 
assessments can be completed in < 1 hour, and questionnaires can be completed in the subject’s home at their leisure. We 
recognize the need to decrease subject burden and have reduced the number of visits by having the subjects’ return their 
devices (ApneaLinkPlus®, Body Media SenseWear Pro Armband®) by mail, a strategy that was successful in the 
pilot/feasibility study.  
 
Screening Measures:  
Screening interview. Respondents to recruitment solicitations will undergo a brief interview (in-person or telephone) to 
determine if they meet initial eligibility criteria. The interview includes the MAP Index.  
Multivariable Apnea Prediction (MAP) Index 93 will be used to identify persons at moderate-to-high risk for OSA. The 
MAP uses the frequency of snoring, breath holding, and snorting, age, sex, and self- reported height and weight to 
determine the likelihood of OSA. The MAP estimates using multiple logistic regression; its positive predictive ability of 
AHI≥10 in patients presenting at sleep disorders centers was 0.79 (p<0.0001).   
ApneaLinkPlus® is an FDA approved level III device for in-home unattended sleep studies (see Figure 3). Previous 
studies found the device to be highly sensitive and specific to diagnose moderate-to-severe OSA. 94-96 The clinical 
guideline by the Portable Monitoring Task Force of the American Academy of Sleep Medicine concluded that level III 
portable devices were appropriate for the diagnosis of OSA in patients with a high pretest probability of moderate-to-
severe sleep apnea.97 The older single channel ApneaLink was evaluated in determining the presence and severity of OSA 
in a recent study by Drs. Atwood and Strollo.98 In a sample (mean age 45.1 + 11.3, 55% female, BMI 35.9 + 9.1) that will 
be similar to ours, the ApneaLink had a sensitivity of 79.0% and specificity of 88.2% for detecting an AHI ≥ 15; for an 
AHI≥ 20 the sensitivity was 100.0% and specificity 92.5% compared to a simultaneous in-laboratory polysomnography. 
The ApneaLinkPlus® that we will use is a 4-channel device that records breaths, respiratory flow, oxygen saturation and 
pulse rate. We will ask enrolled participants to wear the ApneaLinkPlus® for a single night to identify those persons with 
≥10 apneas/hour. The ApneaLinkPlus® has scoring software version v9.2 that analyzes data. Drs. Atwood, Strollo 
(University of Pittsburgh/VAPHS), or Stansbury (West Virginia University) will review all ApneaLinkPlus® studies. At 
the John Dingel VAHS, a similar FDA approved level III device, the NOX-T3, will be used. This device provides the 
same metrics as the ApneaLink Plus®.  
 

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Primary Dependent Measures 
Aim 1: Glycemic control. Objective measures of glycemic control are 1) A1C and 2) serum fructosamine 
a.  The A1C (5 cc serum sample) offers a stable indication of glycemic control over the past 2 to 3 months. The American 
College of Endocrinology suggests a goal of an A1C of 6.5% or less. 99 We will utilize the use of only standardized, in-
laboratory validated assays for A1C testing.  
b.  The fructosamine level (5cc serum sample) measures glycation of serum proteins, it is responsive to changes in the 
patient’s average glucose because the half-life of albumin (about 20 days) is of shorter duration then the A1C. This test 
will show any change in glycemic control over the last 2 to 3 wks. (Optional measure, not done at WVU) 
Aim 2: Diabetes self-management behavior 
a.  The Diabetes Knowledge Test (DKT)100  We will use the first  15 items for subjects who do not use insulin and the 
additional 3 on insulin usage for subjects who are prescribed insulin. The psychometric properties of the items yield an 
alpha ≥ 0.70 for the general test and the insulin-use subscale, which indicates that both are reliable. The DKT takes 
approximately 5-10 minutes to complete. 
b.  The Summary of Diabetes Self-Care Activities (SDSCA)101 is a brief questionnaire about diabetes self-management 
that includes items assessing the following aspects of the diabetes regimen: general diet, specific diet, exercise, blood-
glucose testing, foot care, and smoking. This validated instrument has high inter-item correlations within scales (mean r = 
0.47), with the exception of specific diet; test-retest correlations were moderate (mean = 0.40). It takes 5-10 minutes to 
complete. 
c. Removed the Diabetes Care Profile (DCP) from protocol. 
d. The Body Media SenseWear Pro Armband® provides an objective measurement of physical activity. It was used 
successfully in the pilot/feasibility study and will be used to obtain 7-day 24-hour activity counts. The Body Media 
SenseWear Pro Armband® measures the duration and intensity of activity (daily total energy  
expenditure, number of steps walked, average metabolic equivalent, active energy expenditure) individuals.102 It was 
found accurate in measuring sedentary to high-impact activity; it collects data on sleep duration which can be evaluated 
along with the sleep diary. The armband allows activity not captured directly, such as water aerobics, to be manually 
entered; the software then utilizes an algorithm to determine the energy expenditure. The data will be uploaded to a 
computer, minimizing the potential for recording errors. The activity endpoint will be summarized as the subject’s mean 
daily activity count on days when the monitor is worn ≥ 20 hours. (At site WVU, the BodyMedia SenseWear Pro 
Armband® is not used. A pedometer will be used to obtain the steps walked). 
e.  The Problem Areas in Diabetes (PAID)103 will be used to assess emotional distress related to diabetes management and 
how it is affected by OSA and EDS. The PAID comprises 24 items on a 5-point Likert scale that are summed to provide a 
total score of emotional distress, with higher scores denoting greater distress. The internal reliability is >0.90; it has sound 
concurrent validity as determined by moderate to strong correlations with a range of theoretically-related measures, and 
responsiveness to change during brief psychosocial and educational interventions.103,104 Welch et al.105 showed effect sizes 
between .30 and .65 for the PAID across seven different intensive diabetes psychosocial, educational, and medical 
interventions, indicating good responsiveness. The PAID has demonstrated validity among minority urban patient 
populations.106 It takes 5-10 minutes to complete.  
Secondary Dependent Measures: 
a. Sleep Quality. The Pittsburgh Sleep Quality Index (PSQI)75 is a validated questionnaire that measures the quality, 
duration, and patterns of sleep in adults. It differentiates “poor” from “good” sleep over the past month. A global sum of 5 
or more indicates a poor sleeper. The PSQI has a Cronbach’s alpha of .83 and a test-retest correlation coefficient of 0.85. 
The PSQI takes 5 minutes to complete.  
b. Subjective Sleepiness. The Epworth Sleepiness Scale (ESS)74,110 is an 8-item scale that measures subjective daytime 
sleepiness, respondents are asked to rate the likelihood of falling asleep in situations using a 4-point Likert scale ranging 
from 0 (“never dozing”) to 3 (“high chance of dozing”). The ESS has test–retest reliability (r=.82) and internal 
consistency (Cronbach’s alpha =.88) . The ESS at ≥ 10 has a sensitivity of 93.5% and a specificity of 100% for 
distinguishing pathological sleepiness.111 The ESS takes 2-3 minutes to complete.  
c. Mood. The Profile of Mood States (POMS)76 is a reliable and valid measure of mood states that has been shown to be 
sensitive to sleep deprivation53 and to CPAP treatment of apnea.48 It presents 65 adjectives to rate (1 to 5) feelings during 
the last 7 days. The POMS takes 5 – 10 minutes to complete.  
d. Vigilance. The Brief Psychomotor Vigilance Test (PVT-B).113 will assess vigilance before and after each DEC 
session. The PVT-B is a computer-based reaction time test that was recently developed to evaluate the ability to sustain 
attention and respond in a timely manner to a signal during a 3-minute testing session. There is no difference in sensitivity 
to sleep loss between the PVT and the PVT-B with the lapse threshold reduced from 500 to 355ms. Total lapses, false 
starts, and reaction time will be the outcome measures of the PVT-B. 

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e. Diabetes Empowerment Scale-Short Form measures the psychosocial self-efficacy of people with diabetes. In order to 
allow for a brief overall assessment of diabetes related psychosocial self-efficacy, an eight-item short form of the DES 
(the DES-SF) was developed. The DES-SF was created by choosing items from the original 37 items. The reliability of 
the DES-SF using the original data set was alpha = 0.85. 
 
Additional measures: Demographic, Anthropometric Measures, and Process Measures,  
a) Sociodemographic and Lifestyle Questionnaire.116 Sociodemographic information will be obtained by a questionnaire 
developed for the Center for Research in Chronic Disorders at the University of Pittsburgh. 
b) Health History Questionnaire is a revision of the Charleson Comorbidity Index 117 to capture key information related 
to comorbid conditions and specific questions of interest such as duration of T2DM and medications 
c) BMI/ Body Composition. Height will be measured at baseline. The Tanita-300GS Scale and Body Fat Analyzer will 
be used to weigh subjects and determine body composition. (Regular scale used to weight subjects at WVU) 
d) AADE7 Goal Sheet will be used by the CDE to evaluate progress of self-care activity.  
e) Newest Vital Sign (NVS)118 serves as a screening test for limited health literacy. The NVS is administered using an 
enlarged, laminated food label that requires interpretation of the information and basic calculations of percent calories 
and fat (we will offer paper/pencil for calculation); less than 4 correct answers indicate the possibility of limited 
health literacy.  
f) Adherence. EncoreAnywhere™ will be used in the CPAP machines to measure adherence. EncoreAnywhere will be 
used to measure adherence. The online adherence data will be at least twice during the first week and then weekly. 
Because increased doses of CPAP are associated with improved daytime functioning, 80 we plan to encourage subjects 
to be adherent to CPAP/sham-CPAP all-night, every night. We will objectively measure the pattern of CPAP 
adherence to determine if the subject is a “good user” or “slowly improves” or has less than optimal use and requires 
focused CPAP support to assist with improved CPAP usage.109 If we are unable to use the Encore Anywhere device, 
we will verbally ask participants how many hours they have used the device and check for adherence with data 
automatically collected in the devices memory that can be downloaded and read from the SmartCard.  
g) Activity monitoring will be measured with Omron pedometers. Mean steps walked with the pedometers will be 
compared to individualized goal for steps based on baseline status during the DEC sessions.  
h) Sleep/Activity Diary will be used to record subjective sleep quality and duration, daytime sleepiness, and sleep habits.  
i) Food Diary will be used to record dietary intake for 3 days before the DEC. Diet data will be used by the Diabetes 
Educator to provide participants feedback and help improve eating behaviors.     
j) Connor Diet Habit Survey (Connor DHS)119 will assess eating habits and diet composition. The Connor DHS is a 38-
item multiple-choice questionnaire comprised of 5 sub-scales: (a) cholesterol-saturated fat, (b) carbohydrate, (c) 
beverage, (d) salt, and (e) restaurant eating and recipes. Validity of the DHS was established previously with 24-hour 
dietary recalls (r = .33, p <.01). The Connor DHS requires about 5-10 minutes to complete. The Connor DHS will be 
used at baseline and 6 months. 
k) Rapid Eating and Activity Assessment for Patients (REAP). 107is a dietary assessment tool to briefly assess patient’s 
diet and physical activity. The REAP is a validated instrument with test-retest reliability (r=.86, p<.001) and 
convergent reliability with the Healthy Eating Index108 score (r=.49, p<.0007). This instrument takes about 10 minutes 
to complete.  
l) SF-12v2 Health Survey is a short (12 questions) version of the SF-36v2® Health Survey that measures a patient’s 
subjective functional health and well-being. The SF-12v2 is a reliable and valid instrument that contains the same 
structure as the SF-36v2 with Component Summary Measures (Physical Health and Mental Health) and Scales 
(Physical Health: Physical Functioning, Role-Physical, Bodily Pain, General Health; Mental Health: Vitality, Social 
Functioning, Role-Emotional, and Mental Health). The SF-12v2 takes approximately two to three minutes to 
complete. 
m) Stanford Sleepiness Scale.112 Sleepiness varies during the day. The Stanford Sleepiness Scales, a single question that 
queries sleepiness on a 1-10 scale, is a validated measure of sleepiness or alertness at a specific moment in time. It 
will be asked before and immediately after each diabetes educational/counseling session.  
 
 
Procedures 
Assessment 1. Written and verbal explanation of the purpose, protocol, risks and benefits of the study will be provided 
and informed written consent will be obtained. The subject’s ability to read at the 5th grade reading level and comprehend 
information will be evaluated with questions that ask “if you feel sleepy, should you drive a car or use dangerous 
machines?” Health literacy will be evaluated by the Newest Vital Sign.118 A urine pregnancy test will be done, if 
appropriate. Study staff will perform anthropometric measurements (height, weight, body composition) and a 

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venipuncture to obtain no more than 30 cc blood for A1C, fructosamine, and lipid profile. Waist circumference will be 
measured twice with an inelastic measuring tape. The Project Manager/ Study Coordinator will instruct subjects on how to 
wear the ApneaLinkPlus® device that night when they go to sleep. Subjects’ will be instructed on wearing the SenseWear 
Armband® and filling out the Sleep/Activity/Diet Diary when they wake up and before bedtime for the next 7 days. 
Subjects will be instructed how to complete the questionnaires at home during the next week. They will be given two 
padded pre-paid mail packets: the first for returning the ApneaLinkPlus® the next day and the second to return the 
SenseWear Armband, questionnaires, and the Sleep/Activity /Diet Diary after using them for 7 days. Data from the 
ApneaLinkPlus® will be uploaded and data reviewed by either Drs. Atwood or Strollo (at Pitt/VAPHS) or Stansbury (at 
WVU) to determine the AHI.  When the ApneaLinkPlus® is uploaded, if there is inadequate data to determine AHI 
eligibility, we will contact the participant and ask if they would be willing to repeat the ApneaLinkPlus® at home sleep 
study. 
 
History and Physical. Subjects will have a history & physical by a Nurse Practitioner or Medical Fellow to determine if 
there is any factor that may exclude them from the study. Drs. Atwood, Strollo or Stansbury will determine if subjects 
meet all study criteria for randomization. 
 
Randomization. Subjects who meet all inclusion/exclusion criteria will be randomly assigned by computer program 
(R-track®) using a minimization algorithm with equal allocation to one of two treatment groups: 1) active CPAP set at a 
level of pressure that will abolish nocturnal respiratory disturbances, or 2) sham-CPAP (placebo) where the level of 
pressure will not abolish nocturnal respiratory disturbances. Use of a minimization algorithm will insure treatment balance 
on three factors: 1) the participant’s baseline physical activity levels in terms of mean number of steps per day based on 
the SenseWear Armband® (< 5,000, ≥ 5000),120 2) whether the subject had previous diabetes education, and 3) whether 
the subject is prescribed insulin. Minimization is a form of adaptive treatment allocation in which the probability of 
assignment to the treatment groups does not remain constant, but is determined by the current balance and/or composition 
of the groups. Treatment group assignment will be generated and stored in a secured database. Subjects and all research 
team personnel involved in further data collection will be blinded as to which group the subjects are assigned. The 
University of Pittsburgh site will randomize participants from all the recruitment sites (West Virginia University, 
VAPSHS, University of Pittsburgh).  
 
CPAP Titration Study/Sham-CPAP Titration. The nighttime CPAP titration PSG will be performed in to determine 
the optimal level of CPAP needed to eliminate the subject’s apnea. The CPAP titration PSG will be performed using 
standard techniques,92 with effective CPAP level defined as an AHI <5/hr with the minimum effective pressure for each 
subject. Subjects randomized to the sham-CPAP arm will have titration studies that are performed identically to the CPAP 
titration except the standard CPAP hose will be replaced with the sham-CPAP hose, the modified expiratory valve will be 
attached and pressure at the nose mask will be < 1 cm H2O. The sham CPAP blower will be set at a pre-set level where 
pressure is not transmitted to the subject but produces the blower sound. Subjects will be loaned, without charge, either 
the CPAP or the sham-CPAP machines to take home for 12-wks. Subjects and their bed partners’ will be instructed by the 
Sleep Educator on how to improve their sleep hygiene, OSA and CPAP therapy. Subjects will be encouraged to use 
CPAP/sham-CPAP every night; adherence will be monitored weekly with the EncoreAnywhere™ system. 
 
Diabetes Education/Counseling. The DEC will consist of two (2) one-on-one sessions (a 90 minute session and a 60 
minute session), and a minimum of 3 follow-up phone calls of approximately 15-30 minutes with a diabetes educator that 
will start approximately one week after subjects have started CPAP or sham-CPAP. (see Appendix for Curriculum).  
Subject education will be provided using published educational materials from the American Diabetes Association and the 
American Association of Diabetes Educators.  Partners will be encouraged to attend the sessions. Data from a RCT 
suggests that 3 1-hr individual sessions results in significantly (p-values <.05) decreased A1C and stress associated with 
diabetes management compared to 8-hrs of group sessions.121 Although the content will be interactive and tailored to 
match each individual’s needs and cultural influences, all subjects will receive standardized DEC based on the AADE 
patient competencies (AADE7).39 Subjects will be provided a pedometer to wear each day and a daily goal of steps, which 
will be increased over the 12 weeks to reach at least 7,500 steps per day.122 They will be given 7-day paper diaries and 
asked to record their daily food and beverage intake, physical activity and sleep habits. The diabetes educator will review 
the diaries at each of the two intervention sessions; will provide written and oral feedback on progress made toward 
improving their eating and physical activity habits. Subjects will be instructed on the value of self-monitoring diet and 
exercise to monitor progress to their behavior change goals.123 Subjects will be questioned on sleepiness before and after 
the session with the Stanford Sleepiness Scale.112 Vigilance will be tested before and after each DEC session with the 

9 
 
12 -July-2018 
PVT-B.113  (Clarification in protocol 7.25.2018): The Stanford Sleepiness Scale is a part of the PVT-B Vigilance test. The 
West Virginia University site does not perform the PVT-B testing.  
 
Promotion and Assessment of CPAP Adherence. Our goal is for subjects to use their CPAP/sham CPAP all 
night/every night. We will enhance the procedures for the promotion of adherence that we employed successfully during 
the pilot/feasibility study. The education was refined from the protocol developed by Dr. T. Weaver; she will be assisting 
this proposal as a Consultant. We will utilize motivational enhancing problem solving and review and reinforce principles 
of good sleep hygiene.124 Subjects will receive education prior to starting CPAP therapy, e.g., that comfort is improved 
with the use of heated humidification on CPAP machines.125 All subjects will be shown various masks and permitted to 
select the most comfortable mask interface. Brochures will be developed in simple language describing the study and 
stressing the importance of using the treatment every night. CPAP adherence will be encouraged with a phone call to the 
subjects by a Sleep Educator after the first night of home use. A refinement from the previous study will be that a Sleep 
Educator will evaluate CPAP/sham-CPAP adherence nightly for the first 2 nights then at least twice weekly with the 
EncoreAnywhere™ web-based patient compliance system. The Sleep Educator will phone the subjects at least weekly, 
and intervene to increase adherence.  
 
Assessment 2.  An assessment will be done after 6-wks of CPAP/sham-CPAP use. Subjects will be mailed the 
questionnaires, SenseWear Armband® and the Sleep/Activity/Diet Diary to use for 7-days. They will return to the study 
site with these items and their glucose meter and pedometer. The assessment includes anthropometric measurements and a 
venipuncture to obtain no more than 30 cc blood for A1C, fructosamine and lipid profile. 
 
Assessment 3 with Unblinding/ Debriefing. (week 12- of CPAP/sham-CPAP use).  Subjects will be sent the 
questionnaires, the SenseWear Armband® to use for 7-days before returning for Assessment #3. Subjects will return to 
the study site with those items, their glucose meter and pedometer. In addition, they will bring their CPAP/sham-CPAP 
machines and masks. Anthropometric measurements and a venipuncture to obtain fructosamine, A1C, and lipid profile 
will be done. Prior to being informed of his/her treatment condition, the subjects will be asked to which arm of the study 
they think they were assigned. The Project Manager/ Study Coordinator and/or PI will debrief the subject, answer any 
questions and provide a copy of their sleep and laboratory data.  
 
Crossover to Active CPAP. The crossover to active CPAP is important because of two reasons: 1) ethical considerations 
and 2) and the pilot/feasibility study subjects identified the possibility of eventually being able to try CPAP treatment was 
a major reason they considered participating in the study. VAPHS subjects who were in either the active and sham-CPAP 
group will be directed to the Sleep Center at the VAPHS for follow-up care. Non-VAPHS subjects in the sham-CPAP 
group will be offered the chance to have an actual CPAP titration study, as described above, receive the CPAP education 
and monitoring, and start CPAP. 
Assessment 4. (week 24) All subjects are reassessed as described above; it is the final assessment for those who were 
initially on active CPAP. We will provide those subjects with a summary of their sleep and laboratory data. Those 
subjects that crossed-over to active CPAP will continue.  
 
Assessment 5. (wk 36) Those subjects who crossed-over to active CPAP will have their final assessment (after 24 wks of 
active CPAP) performed as described above. Subject will receive a final debriefing by the Project Manager /Study 
Coordinator and/or the PI and a copy of their sleep and laboratory data.  
 
Measures to Reduce Attrition. To minimize attrition, in addition to the education/counseling session and telephone calls, 
we will offer study participants modest monetary compensation for their time. As part of the total compensation, subjects 
who complete the 12 weeks of CPAP or sham-CPAP when they were blinded to treatment group will receive a $25 bonus 
if they were adherent to CPAP for at least an average of 4 hours a night. Subjects who were adherent to CPAP for an 
average of 6 hours a night will receive an additional $25 bonus. Subjects who complete the entire study (24 wks) with 
active-CPAP will receive a maximum compensation of $270; those on sham-CPAP who then continue to active treatment 
(36 wks) will receive a total compensation of $300. Subjects will be compensated after designated assessment time-points. 
Excluded participants will be compensated for activities they complete.  
Change in protocol 7.12.2018 (all sites) 
• 
Assessment 4 will be the final assessment for both Active and Sham. Subjects originally on Sham will be 
offered 12 weeks of Active treatment, instead of 24 weeks of Active treatment 
• 
Assessment 5 is removed from protocol 

10 
 
12 -July-2018 
• 
The maximum compensation for both Active and Sham is $280 
Data Management. Data processing and management will be conducted in the Center for Research and Evaluation 
(CRE) at the University of Pittsburgh under the supervision of Dr. Sereika, Director of CRE and co-investigator for this 
project. The CRE also provides support for form design, data entry and verification, programming, and data management 
as fee-for-service.  The CRE supports the design and implementation of paper-and-pencil, computer-based and web-based 
data collection forms.  
The  CRE will serve as the data processing center for all data collected. Form design and data management will be 
conducted in the CRE under the supervision of Dr. Sereika, Director of CRE and co-investigator/statistician for this 
project. Oracle (version 11g, Oracle Corp., Redwood Shores, CA) will be used for data management. Data will be 
collected in three forms: paper-and-pencil instruments, electronic monitors, and biological values. For paper-and-pencil 
instruments, Teleform Elite (version 10, Verity, Inc., Sunnyvale, CA), a Windows-based software package for automated 
data entry/verification, will be used for form design, data entry, and data verification.  
For each form, the corresponding Oracle database tables will be initialized for automatic data exportation, and data 
dictionaries will be created. Following data collection all forms will be thoroughly screened for completeness of response 
upon receipt and scanned into the database; therefore, we anticipate that there will be very little missing data due to 
oversights in collection. During verification, erroneous responses will be checked with the source documents and 
corrected before proceeding with further verification. Using the data dictionaries and data editing programs, final range 
checking and contingency checking of responses will be accomplished. After this final data cleaning, summary indices 
and scales will be computed, and the data files for statistical analysis will be created. Data collected using electronic data 
capture methods (SenseWear Pro Armband®) will be uploaded from the devices to the project computer, interpreted using 
the software, exported as an ASCII file, and merged with identifying information into the Oracle database. The biological 
data will be entered in an Excel file at the laboratory then merged with the project’s Oracle database.  The Oracle database 
is maintained on an off-site centralized server housed at the Network Operating Center (NOC) of the University of 
Pittsburgh.  The NOC is a secure, high availability University facility equipped with backup power, redundant 
networking, heating, and cooling, 24-hour staffing, and a data mirror system to create continuous backups.  
Data collection at West Virginia University will be performed by the study team with verification and oversight provided 
by PI, Dr. Stansbury. De-identified data from VAPHS and West Virginia University study participants will be sent to Dr. 
Chasens’ office at the University of Pittsburgh. 
 
C. STATISTICAL ANALYSIS  
 
 Data will be analyzed using SAS (version 9.3., SAS Institute, Inc., Cary, NC) to conduct exploratory data analyses, 
missing data estimation, and repeated measures modeling. Mplus (version 6.12, Muthén & Muthén, Los Angeles, CA) 
will be used for the fitting of mediational models to explore mechanistic pathways. When screening data, the level of 
significance will be set to .05 for two-sided hypothesis testing. Although directional hypotheses have been posited for the 
endpoints associated with the primary aims, a more conservative approach will be adopted and hypothesis testing will be 
nondirectional. Given the multiple endpoints and time points to be examined for the primary aims, the testwise level of 
significance will be set at .01 to limit the inflation of type 1 error. Confidence intervals for point estimates will be 
computed at 99%. 
 
Preliminary Analyses. Detailed exploratory data analyses will first be performed, involving data description and data 
screening for anomalies (e.g., outliers, nonnormality, etc.). The results from this initial investigation will be used to: 1) 
describe univariate and bivariate data distributions; 2) identify imbalances between treatment groups and associations 
between the dependent variables and suspected covariates/confounders); 3) evaluate the amount and patterns of missing 
data; and 4) check for the violation of statistical assumptions for the planned analyses. Covariates/confounders will be 
included in models secondarily and their effect on the results of primary predictors/factors will be evaluated. The 
randomness of missing data will be investigated using available information on subject characteristics to help discern 
patterns in the missing data, identify the possible covert missing data mechanisms, and inform the choice of the strategies 
to handle missing data. It is anticipated that the primary reason for data to be missing will be subject attrition. We will 
closely monitor attrition and conduct logistic regression models via SAS PROC LOGISTIC to compare the characteristics 
of participants who remained in the study versus those who dropped out to determine if data are missing at random. If the 
data are missing at random (i.e., not related to the outcome itself), likelihood estimation procedures, such as those used in 
SAS PROC MIXED, GLIMMIX and NLMIXED as well as Mplus, will produce unbiased estimates while allowing us to 
retain cases with missing values on the outcome variables. If needed, multiple imputation would be used to impute 
missing values on the predictor variables. If the data are not ignorably missing, we use pattern mixture or selection 
modeling to examine data attrition. 

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12 -July-2018 
 
 
Data Analysis Plan for Primary Aim 1. An "intent-to-treat" (ITT) approach will initially be used during data analysis 
when investigating efficacy of CPAP+DEC compared to sham-CPAP+DEC. All subjects will be included in the data 
analysis in the groups to which they were randomly assigned, regardless of the adherence to protocol, treatment received, 
withdrawal or deviation from protocol. Adherence with the assigned protocol, will be monitored throughout the duration 
of the study. With this ancillary information, the sensitivity of the results under the ITT model will be explored to identify 
the effects of the amount of intervention received and the deviations in protocol on the efficacy of the interventions. Since 
the primary endpoint of interest, glycemic control, is assessed repeatedly using two measures, fructosamine and A1C, 
linear mixed modeling (LMM) with linear contrasts to test the stated hypotheses. A flexible modeling approach, mixed 
modeling allows for unequally spaced assessments, fixed and time-varying covariates, dependent variables with data that 
are missing at random, and modeling the covariance/correlation among longitudinal responses. We will consider the 
baseline value both as an assessment point as well as a possible covariate in analyses. The primary independent variable is 
the randomized assignment to treatment (CPAP+DEC vs. sham-CPAP+DEC). Fixed and/or time-dependent covariates 
(including baseline outcome values) may be included in the repeated measures model as indicated secondarily based on 
the results on the preliminary data analysis to adjust for group imbalances or variables related to the dependent variable. 
Prior to fitting the repeated measures model, the structure of the estimated covariance matrix for the repeated measures 
will be carefully examined to determine the appropriate covariance structure. Fit indices will also be used to evaluate the 
repeated measures models estimated assuming different covariance structures to identify the most appropriate covariance 
structure. When fitting models, time will be treated as a fixed, repeated within-subjects factor, while treatment assignment 
will be a fixed, between-subjects factor, with an interaction between time and group. F-tests will be used to test the main 
and interaction effects included in the model. Individual regression parameters will be computed and reported with their 
asymptotic standard errors to yield confidence intervals. Sensitivity analyses will be performed to discern the impact of 
influential cases on results. To test the associated hypothesis (H1), linear contrasts will be specified and estimated when 
fitting the repeated measures model to compare, relative to baseline values, the CPAP+DEC and sham-CPAP+DEC 
groups on: 1) the 6-week values of fructosamine and A1C and the 2) 12-week values of fructosamine and A1C. Wald t-
statistics will be used to test each linear contrast. Confidence intervals will be obtained for these linear contrasts. Marginal 
modeling with generalized estimating equations will also be used as it tends to be more robust to misspecification of the 
covariance structure of repeated assessments and violations in the normality assumption for continuous outcomes. 
 
Analysis Strategy for Aim 2. Using the approach described for Aim 1, repeated measures models will be fitted, and 
linear contrasts will be estimated to compare 6-week and 12-week values for improvements in diabetes self-management 
outcomes (retention of information taught during the DEC classes [DKT], improved self-management behaviors 
[SDSCA], increased physical activity [SenseWare Armband steps], and decreased diabetes-related distress [PAID]) 
relative to baseline values between subjects on CPAP+DEC and those receiving sham-CPAP+DEC. Generalized linear 
mixed modeling or nonlinear mixed modeling will be used to analyze longitudinal categorical outcomes should outcome 
variables need to be categorized for analysis. Along with test statistics and p-values, point and interval estimates will be 
obtained for linear contrasts. 
 
Analysis Strategy for Aim 3. We will explore adherence to CPAP (dose) and specific neuro-behavioral and 
physiological mechanisms (nighttime sleep, daytime sleepiness, mood, and vigilance during DEC sessions) as possible 
intervening, or mediator, variables that may mediate the effects of CPAP treatment on glycemic control and diabetes self-
management outcomes. Initially, we will fit simple mediational models (predictor, single mediator, single outcome) and 
estimate whether the effects of CPAP (predictor) on changes in glycemic control and diabetes self-management outcomes 
are mediated through changes in specific neuro-behavioral and physiological variables (i.e., nighttime sleep, daytime 
sleepiness, mood, and vigilance during DEC sessions). Standardized parameter estimates of path linkages (with 
confidence intervals) will be obtained to summarize associations between the exogenous treatment variables, suspected 
mediators, and distal outcomes, as well as the indirect effect of the treatment group on the targeted outcomes through the 
suspected mediators and the direct effect of the treatment group on the outcomes. The goodness-of-fit of a model will be 
assessed using standard summary indices (e.g., RMSEA, CFI) as well as through residual analyses. Depending on the 
results for testing of individual mediators, we may combine the mediators into a multiple mediator model to develop a 
more complete picture of these hypothesized mechanisms of action for CPAP. 
 
Analysis Strategy for Aim 4. For this aim we will combine the 6 months of data for the two groups receiving CPAP 
(including the participants in the delayed treatment group who crossover to CPAP) to explore retention of treatment 
effects and to explore the association between the durability of treatment of OSA (i.e. adherence to CPAP) and 1) sleep 

12 
 
12 -July-2018 
quality [PSQI], 2) daytime sleepiness [ESS]), 3) mood [POMS], 4) diabetes self-management [SDSA, DES-SF, PAID, , 
and 5) glycemic control [fructosamine and A1C] after 24 weeks of active CPAP. For delayed treatment group participants, 
the initial assessment for this analysis will be their assessments at 12 weeks from study start. Random coefficient 
modeling will be applied to model changes in sleep quality, daytime sleepiness, mood, diabetes self-management and 
glycemic control and to associate these changes with objectively measured CPAP adherence via the EncoreAnywhere™.  
Estimated regression coefficients and confidence intervals will be reported to summarize changes in outcomes over time 
and their associations with CPAP adherence. 
 
Sample Size Justification. The study sample size of 210 was determined focusing on the testing of hypotheses associated 
with the primary aims (Hypotheses 1 and 2) and considering the results of the pilot/feasibility study (reported in 
Approach), the adjustment of the testwise significance level to .01 to limit inflation of type 1 error due the multiple testing 
of hypotheses at 6- and 12-weeks follow-up for several outcomes, and the anticipated subject attrition during the 12-
weeks of follow-up. Regarding Aim 1, our pilot/feasibility study suggests that CPAP improves glycemic control as 
measured by serum fructosamine (see Table 1). Therefore, we anticipate large effects (in terms of standardized mean 
differences, d) on the order of d= -0.74 may be detected with 0.80 power with a group sample size of 48 (96 total) when 
comparing mean changes from baseline to 6 weeks and to 12 weeks in serum fructosamine between CPAP+DEC and 
sham-CPAP+DEC groups using linear contrasts from a repeated measures model at testwise two-tailed level of 
significance of .01. Regarding Aim 2, we have observed effect sizes with magnitudes ranging from 0.22 to 1.27 (median 
effect size of 0.75) for 4-week changes from baseline in physical activity, sleep, vigor, fatigue and vigilance measures (see 
Table 1). Groups of 84 participants (168 total) will be of sufficient size to detect effect sizes as small as d=0.53 in mean 
changes from baseline to 6 weeks and to 12 weeks (based on linear contrasts from a repeated measures model) with 0.80 
power at testwise two-tailed level of significance of .01. Although efforts will be made to retain study subjects, some 
subject attrition is possible. Our recent pilot/feasibility study of active-CPAP with a 4-week follow-up in adults with type 
2 diabetes demonstrated low attrition of 5%. In the CATNAP study (Weaver et al.) about 10% attrition was observed. To 
ensure an adequate number of subjects complete the study by conservatively adjusting sample size for 20% attrition, we 
plan to enroll 210 subjects (105 per group) to have at least 168 subjects (84 per group) complete the study. 
 
Potential Challenges and Strategies. We anticipate two potential problems: 1) management of a large-scale study and 2) 
loss of blinding by research staff involved in data collection. Our strategies are that Dr. Chasens has the support of a 
cohesive team of co-investigators who are recognized in their areas of knowledge and have complementary expertise to 
this project. Our pilot/feasibility study demonstrated that study protocol successfully blinded subjects.79 We have 
developed a diagram of study personnel (see Appendix), duties, and blinding status to demonstrate how we plan to 
maintain blinding. We are aware that reducing subject burden is important. Although we did not have complaints of 
excessive burden in the pilot study and a 95% retention rate, we have further minimized burden with: 1) home testing of 
OSA with the ApneaLinkPlus® and 2) consolidating study activity to eliminate a separate discharge/exit evaluation. The 
two diabetes education sessions are part of standard diabetes care and the one-to-one format is more time efficient than 
regular group classes. The study sites (UPMC and VAPHS) are accessible by bus and we provide free parking to study 
participants. We will monitor seasonality as a potential confounder. We have the team and resources in place to 
implement this vitally significant study that will elucidate the role of sleep disorders as a previously unrecognized but 
significant barrier to the management of chronic disease.  
 
D. 
PROTECTION of HUMAN SUBJECTS  
 
Risks to the Subjects 
Human Subjects Involvement and Characteristics.  
The study sample will be 210 individuals with T2DM recruited from the community or the VAPHS with suspected 
OSA. Verbal consent will be requested from the potential participants prior to the telephone screening. The telephone 
screening will use a script to query for inclusion and exclusion criteria. The PI or Project Manager/ Study Coordinator will 
obtain written informed consent for each study subject at Assessment 1. No study related procedure will be done prior to 
consenting and giving the subject ample opportunity to ask any questions he/she might have. The clinical protocol has 
been developed with the focus on maintaining safety and scientific integrity. Potential CPAP/sham-CPAP subjects will be 
evaluated by a physician or nurse practitioner (not one of the study investigators) to determine that the individual is a safe 
and appropriate subject for the study. Throughout the data collection period of this protocol we will assess for any adverse 
events associated with CPAP/sham-CPAP treatment. 

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12 -July-2018 
Inclusion criteria. Subjects in the final sample who are randomized to CPAP or sham-CPAP will have suboptimal diabetes 
management (A1C ≥ 6.5%), AHI greater than ≥ 10 (ApneaLinkPlus®); age 18 years and older, and willing to be 
randomized to CPAP or sham-CPAP.  
Exclusion criteria. The exclusion criteria are intended to enhance subjects’ safety and ability to complete the study 
protocol.  The table (Table 3) explains the rationale for these exclusions. 
 
 
Sources of Materials.  
All data will be collected solely for the purpose of this study. We will collect the following data for research purposes: 
Trained staff will perform anthropometric measures, calculate BMI, and obtain blood (venipuncture) to be assayed for 
A1C, fructosamine, and lipid profile levels for all subjects. We will ask for urine specimens to determine pregnancy in 
potentially pregnant subjects. We will gauge physical activity and sleep quality/quantity from the SenseWear Armbands® 
and Sleep/Activity diaries and determine adherence to CPAP from a wireless EncoreAnywhere™ device in the 
CPAP/sham-CPAP devices that are uploaded to a secure server. Subjects will be told that their adherence to CPAP is 
being monitored with the devices. We will record vigilance information from the PVT-B and questionnaires that elicit 
data regarding sleep, sleepiness and mood. We will record the results of the ApneaLinkPlus™ and the overnight PSG that 
Table 3: Rationale for Exclusion Criteria 
Exclusion Criteria 
Rationale 
A1C ≥ 11.0% 
These individuals may need changes in diabetes medications 
Type 1 or gestational DM 
Etiology not associated as directly with OSA as T2DM 
Sleep duration < 4 hrs per day 
Inadequate sleep may be confounding barrier in addition to OSA 
Diabetes meds: change in oral medications or > 
10% change in insulin  in last 3 months 
Improvement in diabetes control from med change may confound results 
Acute medical or surgical conditions or 
hospitalization ≤ 3 months (such as angina, 
stroke, major surgery, major depression or 
serious psychiatric conditions) 
Subject may be unstable and inappropriate for clinical trial 
Previous Dx. of another sleep disorder 
Additional sleep disorders may result in continued sleep disturbance 
Oxygen or bi-level PAP required  
Unable to randomize to sham-CPAP 
O2 sat. < 75% for > 25% of the Dx. PSG  
Significant hypoxia presents a danger to delay treatment 
Prior CPAP or persons in household with CPAP 
Increased difficulty in maintaining blinding to CPAP vs sham-CPAP 
Cardiovascular events noted during overnight 
titration sleep study 
Significant cardiovascular events presents a danger to delay treatment 
Hx. of near-miss or auto accident during last 12 
months 
Danger of accident from sleepiness 
Employed in safety sensitive job (i.e. truck 
driver or airline pilot) 
Danger of accident from sleepiness 
Non-ambulatory 
Physical activity with walking is aim of study 
Regular use of hypnotic or alerting (e. g. 
modafinil) medications 
May interfere with nighttime sleep or daytime alertness 
Consumption of alcohol: Men: > 4 drinks a day 
and more than 14 drinks per week 
Women: > 3 drinks a day and > 7 drinks per 
week 
May interfere with nighttime sleep or daytime alertness 
Claustrophobia to wearing mask 
Potentially unable to wear CPAP mask 
Unable to speak, read & write English 
Not able to perform study tests and participate in the DEC sessions 
Pregnant or intend to become pregnant in the 
next four months (postmenopausal or confirmed 
not pregnant by a urine pregnancy test) 
Changes in respiration, sleep, and energy potentially confound the results  
Primary Care Provider request   
Subject may be unstable or otherwise inappropriate for clinical trial 

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12 -July-2018 
measures sleep variables including the AHI. We will obtain information from the titration study that records the optimal 
pressure limit to alleviate episodes of apnea and hypopnea.  
Data will be identified only by subjects’ assigned unique number and will be stored in locked filing cabinets 
accessible only to investigators and project staff. 
Potential Risks 
There are a few potential risks to the proposed protocol. The procedures and standardized tests required by this 
protocol are all standard assessment techniques that are widely used on patients.  The standardized tests employed in the 
project pose minimal risk to subjects. We will also take precautions to ensure that no patient who is sleepy is permitted to 
drive home at the end of an assessment visit. Participants will be informed of the danger of driving while sleepy and asked 
not to drive when experiencing sleepiness. Subjects will be informed that their use of CPAP will be monitored. Except for 
untreated daytime sleepiness, there are no known risks to the application of the sham-CPAP. As described above, there is 
no hazard of CO2 retention or exacerbation of nocturnal symptoms including respiratory events. This placebo has been 
used in previous research without any serious adverse incident (personal interview C. Kushida, APPLES PI, May 29, 
2008) and data from the CATNAP (T. Weaver, Consultant) trial indicates minimal risk to study participants. Subjects will 
experience side effects associated with the technological interface as they would with active CPAP treatment.  
Our consideration of the ethical issues related to the use of the placebo is addressed in that subjects are fully informed 
that they may be on a sham-device during the consent process. The sleep evaluation and treatment of subjects will be 
according to clinical guidelines with the exception of subjects treated with the sham-CPAP intervention. Subjects who are 
assigned to the sham-CPAP will be given the opportunity to participate in a therapeutic use of CPAP at the completion of 
their study. Subjects may feel boredom or stress in filling out questionnaires and may view study requirements as 
burdensome. Subjects may have bleeding, bruising, soreness (infrequent; occurs in 1%-10% of people) and fainting or 
infection at the site of venipuncture (rare; occurs in less than 1%). The ApneaLink Plus risks include the potential for the 
subject to experience nasal mucosa irritation from the cannula (common, occurs in 1-25%) or skin irritation around the 
nose and or behind the ears from the nasal cannula (rare, occurs in less than 1%). There are no risks associated with 
becoming entangled in the breathing tube during sleep. The breathing tube is short (21 inches in length) from the 
recording device to the nose. Mild skin irritation at the site of the finger sensor, similar to what one might experience 
when taking a bandage off is rare (occurs in less than 1%). 
The BodyMedia SenseWear Armband® activity monitor is powered by a rechargeable battery; the chance of a mild 
electrical shock is very unlikely. The monitor fits around the upper arm and is secured with Velcro. There is the unlikely 
possibility of a rash or chafing at the site under the armband.  
Recruitment and Informed Consent   
A record without any identifiers will be kept of all individuals who contacted the study but refused to participate. 
Individuals not consenting to participate will be asked for the reason for their decision. This reason will be documented in 
the tracking system. We will read them a statement asking for voluntary oral permission to participate in the telephone 
screening process. Respondents who do not want to participate in the screening will be thanked and no further questions 
asked. The questions asked in this screening interview pose no more than minimal risk for the potential participants and 
are questions that would not require prior consent outside the research context. Those who meet preliminary eligibility 
criteria will be invited to enroll in the study. Recruitment will be monitored monthly (see Table 4). We will utilize the 
expertise of Drs. Redline and the involvement of the entire research team of investigators and staff in achieving our 
recruitment goals.  
Table 4: Sample Recruitment Monthly Monitoring 
Date 
 
 
 
 
Total Subjects evaluated 
 
 
 
 
Subjects randomized 
 
 
 
 
Men Randomized 
(month/cumulative) 
 
 
 
 
Women Randomized 
(month/cumulative) 
 
 
 
 
Whites Randomized  
(month/cumulative) 
 
 
 
 
Minorities Randomized 
(month/cumulative) 
 
 
 
 
Total Randomized Subjects 
 
 
 
 

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Total Goal for Study (to date) 
 
 
 
 
 
The PI or Project Manager/Study Coordinator, in accordance with the Institutional Review Board (IRB), will obtain 
written informed consent for each study subject. Prior to any data collection, we will provide written and oral explanations 
of the study’s purpose, protocol, risks, and benefits. The candidates will have an opportunity to ask questions and then 
will be asked to sign the form consenting to participate in the study. All advertisements to recruit subjects will be 
reviewed and approved by the IRB. The study’s Steering Committee (PI, Site PIs and the Co-investigators), as well as the 
IRB must agree upon any amendment or revision to the protocol as the trial progresses. One copy of the informed consent 
form will be given to each subject. One signed copy will be retained in the investigator’s study records. At West Virginia 
University the consent will be scanned into the patient’s electronic medical record. 
Protection Against Risk - To prevent adverse events this study will follow IRB review and surveillance. The following 
actions will be taken to protect subjects from risks.  
a) Subjects will be given the National Sleep Foundation “Drowsy Driving Sleep Sheet” to inform them of the risks 
associated with drowsy driving.  
b) The consent form indicates that subjects should not drive when sleepy. Subjects are informed they should report any 
falling asleep while driving events to the Project Manager/ Study Coordinator at the time of the monitoring telephone 
calls during the intervention. 
c) A form called the “Risks of Daytime Sleepiness” will be reviewed with the subject. Questions at the end will be 
answered to indicate understanding.   
d) After the intervention has been initiated, if a subject report falling asleep while driving, their treatment group will be 
unblinded and the subject will be withdrawn from the study.  
e) Questionnaires will be completed in the privacy of the subjects’ home; they will be instructed to take rest periods as 
needed if they find completing the questionnaires as burdensome.  
f) Monitoring physical activity with a SenseWear Armband®, having a venipuncture to draw 30cc of blood by trained 
phlebotomists and responding to questionnaires have only minimal risks to subjects who participate. 
g) Procedures are in place to maintain the security and confidentiality of subject data. All paper-based records will be kept 
in a secure location that is locked and accessible only to personnel involved in the study. The EncoreAnywhere™, a 
patient compliance management system, is a HIPPA approved, secure web-based password protected program that 
contains de-identified adherence data.  Multiple levels of password protection (i.e., record, file, directory, server, and 
computer levels) will ensure data security. All study data will be backed up nightly. The finalized datasets along with 
documentation and their corresponding syntax files for analysis will be stored on the secure centralized server and 
written to a CD for off-site archival. No subject identifiers other than the subject’s assigned unique study identifier will 
be contained in any of the data files or in any of the subject files that are stored in locked filing cabinets. 
h) Sham-CPAP circuits will be inventoried and destroyed after use so that none are used inadvertently by persons other 
then the subjects randomized to that group. 
IRB review and investigator certification:  
Permission to conduct the proposed study will be obtained from the University of Pittsburgh’s Institutional Review 
Board. All study personnel will maintain current certification in Research Practice Fundamentals, as mandated by the 
IRB.  The West Virginia University IRB will approve and monitor study activities conducted on the WVU campus. The 
VAPHS will approve and monitor study activities conducted at the Veterans Administration Pittsburgh Healthcare 
System. 
 
Potential Benefits of the Proposed Research to the Subjects and Others  
There may be a direct benefit to subjects in this study in that all subjects will be provided with two one-on-one DEC 
sessions and three follow-up phone calls with a diabetes educator. In addition, subjects may learn about sleep apnea and 
how to increase their usage of CPAP. As detailed below, the study offers significant potential benefit by providing new 
information about the effect of sleep disorders and related sleepiness on physical activity and outcomes of a DEC program 
in persons with T2DM. Our findings may result in the development and implementation of behavioral interventions to 
promote sleep and improve daytime function in persons with T2DM.   
Importance of the Knowledge to be Gained 

16 
 
12 -July-2018 
Although CPAP has been shown to improve nighttime sleep and daytime function in persons with OSA, we know of 
no published study that has examined whether this treatment for OSA improves outcomes of diabetes management. The 
proposed study will test the hypotheses that treatment of OSA will result in improved glycemic control and diabetes self-
management. The knowledge to be gained is important because it is not known whether sleep disorders act as a barrier to 
learning diabetes self-management, incorporating knowledge of diabetes self-management into lifestyle, or the burden of 
managing a chronic disease. CPAP treatment of OSA, known to improve nighttime sleep and reduce daytime sleepiness, 
may also be conducive to increasing the diabetes self-management of persons with T2DM. We will examine if subjects 
who receive treatment of OSA with active CPAP not only have increased retention of knowledge taught in DSME but also 
to have increased integration of DEC behavioral lifestyle interventions aimed to increase glycemic control. Given the 
strong association between OSA and T2DM, the proposed study will provide much-needed information on the effect of 
CPAP for OSA on diabetes self-management and glycemic control. These potential benefits far outweigh the minimal 
risks of the study. 
 
Data and Safety Monitoring Plan 
We consider subject safety essential. The PI will review reports reflecting data quality, safety, and monitoring as 
indicated in Table 5 and monitor for potential adverse events and protocol adherence. There will be weekly meetings with 
the study staff to review the progress of the study. There will be monthly meetings with members of the investigative team 
to support the study. A Safety Officer who is a physician but independent from the investigative team will be available to 
monitor and oversee subject safety on an ongoing basis. There will be a telephone meeting between the PIs and Project 
Managers/ Study Coordinator of the sites (Pittsburgh, VAPHS and West Virginia University) at least every two weeks. 
All sites will follow their respective IRB policies in reporting AEs/SAEs/UAPs.  
Table 5:   Data Safety Monitoring, Data Type and Frequency of Review 
Data Type 
Frequency of Review 
Site PI, Project Manager and 
Staff 
Site PI, Co-I, Project 
Manager, Staff 
Project Team (Pitt PI and Project 
Manager), DSMB & Safety Officer 
Subject recruitment, 
enrollment, retention 
Recruitment and enrollment 
reports weekly; retention rate 
reports monthly and every 6 
months and at the completion of 
the study  
Monthly and as needed informal 
meetings with Co-investigators. 
Meeting at least twice yearly o 
review subject recruitment, 
enrollment and retention 
Recruitment and enrollment reports 
every 6 months during study, more 
frequently if recruitment issues arise 
and warrant it. 
Adherence to study protocol 
for inclusion and exclusion 
criteria and demographics 
Adherence to inclusion and 
exclusion criteria weekly during 
recruitment and enrollment 
phases of study; adherence to 
demographic criteria every 6 
months  
Monthly and as needed informal 
meetings with Co-investigators. 
Meeting at least twice yearly to 
review adherence to study 
protocol 
Inclusion and exclusion adherence 
reports and demographic adherence 
report every 6 months during study 
Adherence of subjects to 
treatment protocol 
Adherence statistics 
(BodyMedia SenseWear 
Armband®, Sleep/Activity 
Diaries, CPAP adherence) 
monthly & at each scheduled 
assessment and/or data-
collection point, per study 
protocol; at study completion for 
each subject 
Monthly and as needed informal 
meetings with Co-investigators. 
Meeting  at least twice a year to 
review adherence of subjects to 
treatment protocol 
Every 6 months during study 
Adverse event rates 
Immediate notification and 
review for each event; quarterly 
rate reporting 
Immediate notification as 
needed, to review at least twice a 
year. 
Immediate notification and review for 
each adverse event; review report 
quarterly 
Data coding, entry, and 
preparation for analysis 
Monthly 
At least twice a year meeting. 
No review needed 
Subject complaints 
At all project meetings.  
As needed in informal meetings 
with Co-investigators  at least 
twice a year to review.  
Every 6 months and as needed 
Out-of-range laboratory 
values (not expected.) 
PI will contact subjects who 
have out-of-range values and 
recommend their contacting 
their primary physician. If 
As needed informal meetings 
with Co-investigators. At least 
twice a year meeting to review.  
Every 6 months, the PI will send 
reports to the Safety Officers and 
discuss follow-up.   

17 
 
12 -July-2018 
 
A Data and Safety Monitoring Board (DSMB) was created to review this study.  Members consist of persons 
independent of the investigators who have no financial, scientific, or other conflict of interest with the study.  Written 
documentation attesting to absence of conflict of interest will be required.  After initial approval and at periodic intervals 
(to be determined by the committee) during the course of the study, the DSMB responsibilities are to: 
1. Review the research protocol, informed consent documents and plans for data and safety monitoring; 
2. Evaluate the progress of the study, including periodic assessments of data quality and timeliness, participant 
recruitment, accrual and retention, participant risk versus benefit, adverse events, unanticipated problems, 
performance of the trial sites, and other factors that can affect study outcome; 
3. Consider factors external to the study when relevant information becomes available, such as scientific or therapeutic 
developments that may have an impact on the safety of the participants or the ethics of the study; 
4. Review clinical center performance, make recommendations and assist in the resolution of problems reported by the 
PI; 
5. Protect the safety of the study participants; 
6. Report on the safety and progress of the study; 
7. Make recommendations to the PI, and if required, to the NIDDK concerning continuation, termination or other 
modifications of the study based on the observed beneficial or adverse effects of the treatment under study; 
8. Monitor the confidentiality of the study data and the results of monitoring;  
9. Assist the PI by commenting on any problems with study conduct, enrollment, sample size and/or data collection. 
The DSMB will include experts in clinical trials, diabetes, sleep medicine, and biostatistics.  Members will consist of 
persons independent of the investigators who have no financial, scientific, or other conflict of interest with the study.  
Written documentation attesting to absence of conflict of interest will be required. 
The University of Pittsburgh Office of Clinical Research, Health Sciences will provide the logistical management and 
support of the DSMB.  A safety officer (chairperson) will be identified at the first meeting.  This person will be the 
contact person for serious adverse event reporting.  Procedures for this will be discussed at the first meeting. 
The first meeting will take place before initiation of the study to discuss the protocol, approve the commencement of 
the study, and to establish guidelines to monitor the study.  The follow-up meeting frequency of the DSMB will be 
determined during the first meeting.  An emergency meeting of the DSMB will be called at any time by the Chairperson 
should questions of patient safety arise.  
The PI will report any adverse events to the University of Pittsburgh IRB and will notify the WVU IRB and the DSMB 
Chair/Officer. No protocol modification will be instituted without IRB approval.  
 
Unmasking (Unblinding) of Treatment 
If there is a serious adverse event, anticipated to be an uncommon occurrence, the PI, Medical Directors, Safety 
Officer or DSMB will, when necessary for the safety of the participant, unmask treatment group assignment. The 
administration of the intervention may be discontinued at the patient’s request or by the investigator, based on clinical 
judgment. Participants will be instructed to report any adverse event experienced after treatment without delay.   
Protection of Confidentiality 
No personal identifiers will be connected with the data. A unique study identification number will be assigned to each 
participant and a log accessible only to the investigators and key study personnel will link the study identification number 
to medical record numbers, when applicable. Only appropriate and authorized personnel are able to view, access, and 
modify study data.  Data result (results of ApneaLinkPlus®, titration PSG, and laboratory results) will be sent only to the 
Primary Care Provider that has been indicated with the subject's permission as noted in their informed consent. No data 
from questionnaires or other variables will be shared with any other persons. No data on participants' use of CPAP will be 
provided to any caretaker or company involved in the clinical management of patients or in the provision of equipment for 
this study.  
immediate attention is 
warranted, with subject’s 
permission, the PI will notify the 
subject’s physician.  

18 
 
12 -July-2018 
Each subject in the study will be assigned a unique study code number to be used on all data forms. A list of participant 
names and code numbers will be maintained separately. Only the investigators and project staff will have access to this 
information. All personally identifiable information will be kept strictly confidential and in a locked file cabinet.  
Evaluation of the Risk / Benefits of the Proposed Research to the Subjects and Others 
There is no direct benefit to subjects in this study other than the diabetes education and counseling sessions. The study 
has minimal risks and the significant potential benefit of the proposed study is the importance of the knowledge to be 
gained. The proposed study will add to the existing knowledge about the effect of treatment of OSA and 1) diabetes self-
management outcomes and 2) glycemic control in persons with T2DM. Potentially, this knowledge will expand our 
understanding of the effect of sleep disturbances on diabetes self-management which may lead to improved guidelines for 
screening and treatment of OSA in this population.   
Research Study Costs 
No procedures that are part of the protocol will be charged to the subject or his/her insurance provider (ApneaLink 
Plus home sleep study, titration sleep study, CPAP machine).   
 
Research Study Compensation 
Research subjects will not be charged for any of the procedures performed for the purpose of this research study. 
Compensation will be provided for their time for each component of the protocol completed (Table 6). Subjects will need 
to travel to study sites for their evaluations and the DEC sessions. Each assessment at will take about 1 ½ hours and 
includes a venipuncture for a blood sample. Questionnaires take approximately 1 hour to complete at home. DEC sessions 
with CPAP adherence monitoring, the Stanford Sleepiness Scale and PVT-B testing will be also take approximately 1 ½ 
hr. Assessments and DEC sessions may result in some subjects’ potentially missing work. Adherence to CPAP is 
problematic both in research and clinical practice, adherence to CPAP/sham-CPAP is important for the successful conduct 
of this study therefore we have a small bonus for those subjects who are adherent for more than 4 hours a night and an 
addition small bonus who are adherent for an average of 6 or more hours a night. Subjects in the active treatment arm who 
complete all assessments will receive a maximum of $ 280 (US) and those assigned to the placebo sham-CPAP arm 
completing all assessments will receive a maximum of $ 310 (US) since this group completes one additional evaluation 
and 12 weeks of addition participation. There is no reimbursement for the crossover titration study. Persons excluded 
during the process of the study will receive compensation according to the table. The revised participant incentives are 
appropriate $7.50/hr for the time involved participating in the study.  
 
Table 6: Research Study Compensation 
Activity in Protocol 
Compensation 
Total 
Compensation 
Active CPAP 
Total 
Compensation 
Sham CPAP 
Assessments  
$20  
$ 80 (Assessments 
1, 2, 3 & 4) 
$100 (Assessments 
1, 2, 3, 4 & 5) 
ApneaLinkPlus™ Screening 
$10 
$10 
$10 
ApneaLinkPlus™ 2nd Screening 
**(only if needed) 
$10 
$10 
$10 
SenseWear Pro Armband® & Diary  
 
$10/ 7-days   
 
$40 (Assessment 
1, 2, 3 & 4) 
 
$50 (Assessments 
1, 2, 3, 4 & 5) 
History and Physical  
$10 
$10 
$10 
Overnight CPAP titration or sham-
CPAP titration study 
 
$50 
 
$50  
 
$50  
Education Sessions  
$10/session 
$30 
$30 
CPAP /sham CPAP adherence  
$25 if device used 
≥4 hours night/ 
additional $25 if 
device used ≥ 6 
hours night) 
$50 
$50 

19 
 
12 -July-2018 
Totals for CPAP and sham-CPAP 
participants (maximum) 
 
$280 
 
$310 
 
 
Subjects will be compensated a maximum amount if fully adherent to the protocol at these time-points: for the active-
CPAP group: after Assessment 1 material is returned ($40), after 2nd ApneaLinkPlus™ home sleep study (if appropriate 
and necessary) ($10), after the history/physical and overnight titration PSG CPAP/sham-CPAP titration study ($60), after 
the diabetes education sessions (3 2) and Assessment 2 ($60), Assessment 3 ($30) plus an additional $25 if the device is 
used an average of 4 hours per night, plus another $25 if the device is used an average of 6 or more hours per night, and if 
continuing on to crossover, Assessment 4 ($30). Compensation will occur for the sham-CPAP group: after Assessment 1 
material returned ($40), after 2nd ApneaLinkPlus™ home sleep study (if appropriate and necessary) ($10), after the 
overnight titration PSG CPAP/sham-CPAP titration study ($60), after Assessment 2 ($60), Assessment 3 ($30) plus an 
additional $25 if the device is used an average of 4 hours per night, plus another $25 if the device is used an average of 6 
or more hours per night, and if continuing on to crossover, Assessment 4 ($30), and Assessment 5 ($30). Subjects will be 
compensated after designated assessment time-points. Excluded participants will be compensated for activities they 
complete. 
 
University of Pittsburgh Subjects will receive up to $7.50 reimbursement for bus transportation via the WePay System. 
Parking is provided for those who drive. This is being added as bus costs were included in the NIH approved budget. 
 
 
UNIVERSITY OF PITTSBURGH COORDINATING CENTER 
The University of Pittsburgh PI is responsible for the design and development of the protocol; design and development of 
case report forms / data collection tools; randomization, and tracking subject enrollment; tracking, reporting, and 
maintaining serious adverse events and unanticipated problems involving risk to subjects or others, and dissemination of 
information to all sites; ensuring that the affiliated sites are using the correct version of the IRB protocol and consent 
documents and maintain IRB approval throughout the conduct of the study; data management, including transmission, 
storage, and analysis; and recording and distributing devices. 
The University of Pittsburgh Coordinating Center will be responsible for providing periodic updates to all sites on subject 
enrollment, study progress, and any change in the science that potentially impacts the study. 
At least every other week there will be a meeting by telephone to update the sites on recruitment and progression of 
participants. Data will be provided to the University of Pittsburgh DSMB at least every 6 months on subject enrollment 
and study progress that includes the number of subjects screened, consented, and completing each assessment periods. 
The University of Pittsburgh Coordinating Center will monitor, on a periodic basis, the external sites to assess research 
study progress and compliance with the IRB approved protocol. This will be performed by reviewing site standard 
operating policies and monitoring data for accuracy received from the sites. 
The University of Pittsburgh Coordinating Center will monitor, on a periodic basis, that the external sites are using the 
correct versions of the IRB, consent documents, and maintaining IRB approval by collecting and maintaining these 
documents. 
Data processing and management for all the sites will be conducted in the Center for Research and Evaluation (CRE) at 
the University of Pittsburgh under the supervision of Dr. Sereika, Director of CRE and co-investigator for this project. 
The University of Pittsburgh Coordinating Center will maintain records of all devices used in the study. 
The University of Pittsburgh Coordinating Center will maintain responsibility for the federal reporting of the study to the 
NIDDK. 
The University of Pittsburgh Coordinating Center will be responsible for the training of research staff at each site for all 
of the research procedures and requirements that are required for that site. This will be done prior to the initiation of the 
protocol at each of the sites. 
INCLUSION OF WOMEN AND MINORITIES  
Inclusion of Women 
No one will be excluded from the study based on race, gender, HIV status, or ethnicity. Our goal is to enroll 
approximately 50% women in the study. We were successful in the recruitment of women in the completed pilot/ 
feasibility study with the sample screened including 55% women and the randomized sample 41% women. We will recruit 

20 
 
12 -July-2018 
a total of 105 women and 105 men to obtain a final sample of 210 subjects who are 18 years of age or older. The ratio of 
men to women with T2DM is approximately 50:50. We recognize that the risk for OSA is 2.0 to 3.7 times greater in 
men126,127 and that potential subjects from the VAPHC are predominantly male. We plan to recruit approximately 60% of 
the non-VAPHS sample as women and will make special efforts at the VAPHS to target women veterans by focusing 
recruitment activities to the VA Pittsburgh Healthy Women’s Center and to women within the other clinics. In addition, 
our study advertisements will be designed to recruit women and we will attend health fairs that are specifically directed 
toward women.  
 
Inclusion of Minorities 
Our goal is to have a generalizable sample by enrolling at least 40% minority in the study. We exceeded that number 
in the completed R21 pilot/feasibility study which included 53% minority subjects screened (41% African American, 3% 
Asian, 9% Bi-racial [African American and American Indian]) and 45% minority subjects randomized (41% African 
American and 4% Bi-racial). There remains a paucity of data regarding the risk of OSA by racial group. Redline and 
colleagues have reported that the risk of OSA for African Americans compared to Whites aged 26-55 is approximately 
equal (14 vs. 17%). 128 The estimated prevalence of T2DM in African Americans is 2-4 times that of Whites. 129 We will 
attempt to over-recruit minorities considering the racial distribution in the greater Pittsburgh area  (27% African 
American, 3% Asian-American, <1% American Indian, 1.3%Hispanic). Utilization of the VAPHS site will assist in our 
recruitment of minorities with a large percentage of their patient population being African American. We will monitor 
recruitment of minorities and women every month during subject accrual and if we have not met quarterly goals, we will 
contact the recruitment specialists at the CTSI on methods to increase recruitments within the community and again attend 
health fairs at churches and community agencies.  
If it is necessary to enrich the number of potential participants for a particular gender or ethnic group, Dr. Susan Redline, 
Professor at Harvard Medical School, will serve as a consultant for the recruitment of women and minority subjects. It is 
anticipated that the planned actions for retention of all subjects, such as the education session and weekly telephone calls 
will help retain women and minority subjects. The Data Safety Monitoring Board (DSMB) will closely monitor the 
recruitment and retention of women and minority participants.   
 
INCLUSION OF CHILDREN 
This study includes children older than 18 years because T2DM and OSA are known to affect this age group. At this 
age there is less difference in the epidemiology, pathogenesis, symptomatology, diagnostic criteria, and treatment of OSA 
between children and adults.  
Neither the intervention nor the outcome measures are appropriate for younger children. Although T2DM has been 
found to exist among young children (under 18 years), there is no prevalence data on T2DM in this population. Given the 
significant differences in OSA in the younger pediatric age group (under 18 years) and the OSA of adults, the inclusion of 
younger children in this clinical trial may not be appropriate. Further, there are issues of study design that preclude the 
involvement of younger children in this trial. First, the pediatric age group is not of legal age to provide informed consent. 
This is an issue of great concern given that the use of sham CPAP is potentially dangerous in the pediatric age group. 
Additionally, participation in this randomized clinical trial would not confer any direct benefit to the individual child 
enrolled, particularly if the child was randomized to the sham CPAP arm. Another difficulty in children is that 
tonsillectomy is the primary treatment option for the majority of young children with OSA. In contrast, CPAP is used as 
first line therapy for only a small minority of young children. Finally, many of the instruments used to measure outcomes 
in this study (SenseWear Pro Armband®, ESS, POMS) either are not applicable to young children or have not been 
validated in this under 18 years age group.  
 
 
 
 

21 
 
12 -July-2018 
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