Targeting Physical Health in Schizophrenia: Physical Activity Can Enhance Life Randomized Control Trial
Phase: NA
Conditions: Schizophrenia, Schizoaffective Disorder, Brief Psychotic Disorder, Schizophreniform Disorders, Unspecified Schizophrenia Spectrum and Other Psychotic Disorder
Sponsor: University of North Carolina, Chapel Hill

 
 
 
 
 
Targeting Physical Health in Schizophrenia: 
Physical Activity Can Enhance Life 
Randomized Control Trial 
 
 
NCT04173572 
Protocol Date:  June 16, 2021 
 
 

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Clinical Protocol 
 
Targeting Physical Health in Schizophrenia:  
Physical Activity Can Enhance life 
(PACE-Life) 
Randomized Controlled Trial (RCT) 
Version 2.0 
Protocol Date:  June 16, 2021 
 
David L. Penn, PhD 
Principal Investigator 
University of North Carolina at Chapel Hill (UNC-CH) 
250 Davie Hall 
Chapel Hill, NC, 27599 
Phone (919) 843-7514 
dpenn@email.unc.edu 
Claudio Battaglini, PhD 
Co-Principal Investigator 
University of North Carolina at Chapel Hill (UNC-CH) 
105 Fetzer Hall 
Phone (919) 843-6045 
Claudio@email.unc.edu 
 
Co-Investigators 
University of North Carolina at Chapel Hill (UNC-CH) 
Lars Fredrik Jarskog, MD 
Paschal Sheeran, PhD 
Durham VA 
Julia Browne, PhD 
 
 
 

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This study is sponsored by the National Institutes of Mental Health 
TABLE OF CONTENTS 
TABLE OF CONTENTS ....................................................................................................... 2 
ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................................ 3 
PROTOCOL SYNOPSIS ...................................................................................................... 4 
1 BACKGROUND AND RATIONALE ................................................................................... 7 
2 RESEARCH DESIGN AND METHODS ............................................................................. 10 
2.1 OVERVIEW ............................................................................................................ 10 
2.2 SUBJECTS .............................................................................................................. 11 
2.2.1 INCLUSION CRITERIA ...................................................................................... 11 
2.2.2 EXCLUSION CRITERIA ...................................................................................... 12 
3 ASSESSMENT OF DATA ............................................................................................... 12 
3.1 OUTCOMES .......................................................................................................... 12 
4 STUDY DESIGN ............................................................................................................ 13 
4.1 INTERVENTION ..................................................................................................... 13 
4.1.1 GOAL-SETTING ............................................................................................... 14 
4.1.2 FITBITS ........................................................................................................... 14 
4.2 STUDY PROCEDURES AND MEASUREMENTS ......................................................... 14 
4.2.1 SCREENING VISIT ............................................................................................ 14 
4.2.2 BASELINE, MID-POINT, POST-TEST, 1 MONTH FOLLOW-UP............................. 14 
5 STATISTICAL ANALYSES ............................................................................................... 16 
5.1 DATA ANALYTIC PLAN ........................................................................................... 16 
5.2 POWER ANALYSIS ................................................................................................. 16 
5.3 DATA MANAGEMENT ........................................................................................... 16 
6 RISKS AND BENEFITS ................................................................................................... 17 
6.1 MONITORING RISKS .............................................................................................. 17 
6.2 NON-SIGNIFICANT RISK DOCUMENTATION ........................................................... 18 
6.3 POTENTIAL BENEFITS OF RESEARCH TO SUBJECTS AND OTHERS ............................ 18 
6.4 CONFIDENTIALITY OF DATA .................................................................................. 18 
7 DATA SAFETY AND MONITORING PLAN ...................................................................... 18 
7.1 ADVERSE EVENTS .................................................................................................. 18 
7.2 SERIOUS ADVERSE EVENTS ................................................................................... 19 
7.3 DEATH .................................................................................................................. 19 
7.4 PREGNANCY ......................................................................................................... 19 
8 RECRUITMENT STRATEGY ........................................................................................... 20 

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9 CONSENT PROCESS ..................................................................................................... 20 
10 REFERENCES ............................................................................................................. 21 
ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
6MWT 
6-minute walk test 
ACSM 
American College of Sports Medicine 
AE 
Adverse Event 
BMI 
Body Mass Index 
BPNES 
Basic Psychological Needs in Exercise Scale 
BREQ-2 
Behavioral Regulation in Exercise Questionnaire-2 
CRF 
Cardiorespiratory fitness 
CSQ-8 
Client Satisfaction Questionnaire 
CVD 
Cardiovascular Disease 
DSC 
Data Safety Committee 
DSM-V SCID 
Structured Clinical Interview for DSM disorders 
FDA 
Food and Drug Administration 
HRR 
Heart Rate Reserve 
IPAQ 
Short Form International Physical Activity Questionnaire 
NCPRC 
North Carolina Psychiatric Research Center 
OPTMH 
Organization of Physical Therapy in Mental Health 
PA 
Physical Activity 
Pace-Life 
Targeting Physical Health in Schizophrenia: Physical Activity Can Enhance life 
PACES 
Physical Activity Enjoyment Scale 
PAGEQ 
Physical Activity Group Environment Questionnaire 
PANSS 
Positive and Negative Syndrome Scale PANSS 
PAR-Q 
Physical Activity Readiness Questionnaire 

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RCT 
Randomized Control Trial 
RHR 
Resting Heart Rate 
SAE 
Serious Adverse Event 
SDT 
Self-determination Theory 
SSD 
Schizophrenia Spectrum Disorder 
STEP 
Schizophrenia Treatment and Evaluation Program 
WAI-SR 
Working Alliance Inventory (Group) – Short Form Revised 
WASI 
Wechsler Abbreviated Scale of Intelligence 
WRAT 
Wide Range Achievement Test 
 
 
 

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PROTOCOL SYNOPSIS 
Study Title 
Targeting Physical Health in Schizophrenia: Physical Activity Can 
Enhance life (PACE-Life) 
Funder 
National Institutes of Mental Health 
Clinical Phase 
Phase II 
Study Rationale 
The purpose of the PACE-Life trial is to develop and test the 
feasibility of an exercise intervention that combines group walking, 
activity tracking, and heart rate monitoring, and determine the 
effectiveness of this intervention on the physical and mental health 
for individuals with schizophrenia spectrum disorders. 
Study Objective(s) 
1. Feasibility- Can PACE-life be delivered within this treatment 
setting? 
2. Tolerability- How well is PACE-life accepted by the subjects?  
3. Intervention adherence 
4. Evaluation of PACE-life 
Test Article(s) 
(If Applicable) 
Fitbits Charge 3 devices, worn on the wrist, will be utilized to track 
daily steps, minutes spent walking, and monitor HR throughout 
exercise sessions. These devices will also be used to facilitate the 
individualized/home-based component and goal-setting. 
Study Design 
 
This is a two arm (fitbit only vs. fitbit + exercise intervention 
group), randomized controlled trial with 56 subjects (multiple 
groups occurring consecutively ranging from 13-18 participants). 
Subject Population 
key criteria for Inclusion 
and Exclusion: 
Inclusion Criteria 
1. DSM-V diagnosis of a SSD (Schizophrenia, Schizoaffective 
Disorder, Brief Psychotic Disorder, Schizophreniform Disorder, 
and Unspecified Schizophrenia Spectrum and Other Psychotic 
Disorder) 
2. Between the ages of 18-65, both genders, and any ancestry; 
3. IQ>70 and/or reading level at, or above the 4th grade. IQ will be 
assessed using the Wechsler Abbreviated Scale of Intelligence 
(WASI) and the Wide Range Achievement Test (WRAT). 
4. No hospitalizations for psychiatric reasons in the last 3 months 
5. Clinically stable (no psychiatric medication changes within the 
past month) 
6. Are not already engaging in consistent moderate-intensity 
exercise (cutoff = 60 min/week for the past 6 months); 

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7. Present with no contra-indication to engage in regular 
moderate intensity exercise based on the American College of 
Sports Medicine guidelines. (If an individual answers yes to one 
item on the of the Physical Activity Readiness Questionnaire 
(PAR-Q), she/he will be asked to get clearance from a physician 
prior to participating in the study) 
8. Willing and able to provide informed consent.  
Exclusion Criteria 
1. Pregnant women will be excluded because pregnancy alters 
autonomic and immune responsiveness, increase weight gain, 
and can influence heart rate. 
Number Of Subjects  
56 individuals with schizophrenia spectrum disorders 
Study Duration 
Each subject’s participation will last 5 months, 4 months of 
intervention and a 1 month follow-up 
Study Phases 
Screening 
Study Treatment 
Follow-Up   
Pre- Screening- Will be completed prior to the first in-person visit 
via a telephone screen for study eligibility. 
Screening- Subjects who are deemed eligible will be brought on 
site, or virtually via HIPAA-compliant Zoom video call, to obtain 
consent and complete the screening assessments (Demographics, 
WASI/WRAT, a licensed physician will complete a medical history 
and physical exam, PAR-Q. 
Baseline, Mid-point, Post-test, and 1-Month Follow-up- Subjects 
will complete the Demographics, Minutes Spent Walking, the 
Positive and Negative Syndrome Scale (PANSS), the Short Form 
International Physical Activity Questionnaire (IPAQ), Steps/day, 
Cardiorespiratory fitness (CRF)- CRF will be measured using the 6-
minute walk test (6MWT), Chair-Rise Task, 2-minute Step Test, Self-
determination Basic Needs, the Basic Psychological Need Scale-in 
General, the Basic Psychological Needs in Exercise Scale (BPNES), 
Resting Systolic/Diastolic Blood Pressure and resting heart rate 
(RHR), autonomous motivation will be measured with the 
Behavioral Regulation in Exercise Questionnaire-2 (BREQ-2), 
enjoyment of walking will be measured with the Physical Activity 
Enjoyment Scale (PACES), the UCLA Loneliness Scale, Weight, BMI, 
and Waist/hip Circumference: study intervention/experimental 
treatment. CRF will also be calculated using an equation by 
Jackson, A. S., et al. 1990 (119) that includes recent weight and 
height for the calculation of BMI, gender, self-reported physical 
activity level, and age. 

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 At the baseline assessment, subjects will be provided with a Fitbit 
wristband and instructed how to use it. At the conclusion of the 
trial, investigators will administer a brief questionnaire to the 
subjects regarding satisfaction and acceptability. 
Study Treatment- Walking groups will occur twice per week for 30 
minutes. The intensity of both group walks and home-based walks 
will increase throughout this intervention in a stepwise fashion to 
create an exercise dose response to maximize impact on CRF. 
During the COVID-19 pandemic, participants will participate in 
group walks via Zoom video meetings twice per week, starting at 
15-minute sessions and progressing to 30-minute sessions, where 
group leaders will lead participants through exercise sessions. 
Efficacy Evaluations 
Primary outcome- 6MWT will be used to measure CRF during which 
individuals will be asked to walk continuously for six minutes on a 
flat, indoor surface around cones (separated by 100ft). 
Supplemental CRF measures will also be used. CRF will be 
calculated using an equation by Jackson, A. S., et al. 1990 that 
includes recent weight and height for the calculation of BMI, 
gender, self-reported physical activity level, and age. Finally, 
participants will complete the Chair-Rise Task, and the 2-minute 
Step Test to measure CRF. 
Secondary outcomes- Psychological- UCLA Loneliness Scale will be 
used to assess subjective feelings of loneliness. The PANSS will be 
utilized to assess psychiatric symptoms. 
Secondary outcomes- Biological- We will measure weight, BMI, and 
waist circumference at all in-person assessments. We will examine 
these characteristics to determine if they changed as a result of 
increasing exercise. Resting Systolic/Diastolic Blood Pressure and 
RHR will also be assessed following standardized procedures. 
Safety Evaluations 
A safety plan for the walking groups will be developed prior to the 
initiation of the study with Drs. Battaglini and Jarskog, as well as 
the study clinicians. 
Statistical And Analytic 
Plan 
Analyses will primarily be descriptive in nature. We will calculate 
means, standard deviations, and within-group effect sizes of the 
primary outcome (CRF) and secondary outcomes (loneliness, 
symptoms, weight, BMI, waist circumference, resting heart rate, 
and blood pressure). Additionally, we will examine means, 
standard deviations, and within-group effect sizes of intermediate 
targets (self-determination basic needs and autonomous 
motivation) and proximal outcomes (minutes spent walking and 
daily steps).  

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DATA AND SAFETY 
MONITORING PLAN 
Dr. Jarskog will function as the Project Medical Officer. An 
independent physician will serve as the Medical Monitor (Dr. Karen 
Graham, from the Department of Psychiatry).  
 
 
 

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1 
BACKGROUND AND RATIONALE 
 
Individuals with schizophrenia spectrum disorders (SSDs) have a life expectancy up to 25 years shorter 
than individuals in the general population primarily due to elevated levels of chronic physical and medical 
illnesses (1-4). Premature mortality in this population may be explained by high levels of six known modifiable 
risk factors for mortality: high blood pressure, smoking, raised glucose, physical inactivity, obesity, and high 
cholesterol (5-7), with physical inactivity and smoking being the strongest contributors to this risk (8, 9). 
Specifically, cardiorespiratory fitness (CRF) impacts not only cardiovascular mortality but also all-cause 
mortality (10-13), including in individuals with SSDs. Thus, physical inactivity contributes to significantly 
elevated rates of chronic medical diseases, especially cardiovascular disease (CVD) in individuals with SSDs (1, 
5, 6, 14, 15). Further, despite reductions in mortality from CVD in the general population over the past 20 
years, rates in people with SSDs have remained high (16, 17). Indeed, sedentary behavior and poor CRF among 
individuals with SSDs relative to the general population (13, 18-21) are likely major contributors to the 
premature mortality in this at-risk population. As a result, the potential benefits of interventions that increase 
physical activity (PA) in this population are substantial and could have a meaningful impact on public health. 
Studies examining the effects of exercise on physical and mental health in individuals with SSDs have 
yielded encouraging results (22-24). Indeed, well-designed multi-component interventions that target exercise 
and diet, such as the ACHIEVE trial and the In SHAPE program, led to weight-loss and improved fitness in 
individuals with serious mental illness (25-27). However, these findings are tempered by questions of long-
term accessibility and sustainability. Specifically, the In SHAPE program involved individual meetings with a 
trainer and continued access to a gym, perks that are inaccessible to most individuals with SSDs after study 
completion (26, 28-33). While a strength of the ACHIEVE trial was housing it in psychiatric rehabilitation 
settings, not all people with SSDs have access to such programs. In addition, attendance at the intervention 
sessions waned after the first 6 months of the study, which the authors attributed to hospitalizations and 
social issues (19) (p. 1601); however, decreasing subject motivation may have also played a role. 
Prior work has been largely unsuccessful in overcoming the many barriers faced by individuals with 
SSDs. Specifically, exercise participation is hampered by lack of access and cost (e.g. personal trainers), 
biological factors such as physical health problems, social variables such as loneliness and limited social 
support, and self-regulatory problems (e.g., forgetting to exercise, being overwhelmed) (34-43). And, most 
interventions fail to address motivation, a critical factor for initiating and sustaining exercise, particularly for 
people with SSDs (44). Ironically, even work that has directly targeted motivation in this population (45) 
observed difficulties in promoting long-term adoption and sustained exercise after the program ends (46). 
These findings speak to the need for additional strategies to sustain motivation and ensure the effective 
translation of motivation into action. Thus, interventions aimed at this population should be designed and 
delivered in ways that address the substantial barriers to exercise, so as to promote the adoption and long-
term maintenance of physical activity (47, 48). 
Given the importance of motivation and translating intentions to actions, our treatment model is 
rooted in both self-determination theory (SDT) (49, 50) and implementation intentions (i.e., if-then plans) (51). 
SDT is a prominent theory of motivation which is highly suited for exercise interventions (52). SDT posits that 
the fulfillment of three basic psychological needs: autonomy, relatedness, and competence facilitates 
autonomous motivation (i.e. motivation due to one’s own choice rather than as a result of external factors) 
(50). Autonomous motivation, in turn, is associated with levels of exercise participation in the general 
population (52, 53) and in people with SSDs (54).  

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If-then plans have the structure if (opportunity/obstacle)-then I will (response) and engender 
associations that mimic the effects of habits (55). If-then plans create mental links between good 
opportunities to act and responses that move the person towards their exercise goal (e.g., If I have to go 
shopping for 1-2 items, then I will walk rather than drive to the store!”) or between obstacles to exercise and 
responses that will be effective in overcoming those obstacles (e.g., “If I am tempted not to exercise, then I 
remind myself how proud I feel at the end of the session!”). Two separate meta-analyses revealed that if-then 
plans were highly effective in increasing physical activity [ES = .31 and.38] (56, 57)] and led to sustained 
behavior change one year (58-61) and two years (62, 63) post-treatment. If-then plans have also 
demonstrated effectiveness among samples with psychiatric and clinical diagnoses (64) including people with 
SSDs (65). Importantly, autonomous motivation and if-then plans are known to combine synergistically, and 
engender better outcomes compared to the use of either strategy on its own (66, 67). 
In addition to considering motivation and intention translation, we also sought to develop an exercise 
intervention that involves minimal staff resources, that is free and easy to access, and has the potential for 
long-term sustainability. Thus, we chose an intervention that requires no equipment or special training, and 
can be done anywhere: Walking (68, 69). Research has shown that walking leads to improved physical health, 
well-being, and weight loss (70-73). Furthermore, walking without dietary change has been shown to improve 
CRF (10, 74, 75), and reduce the risk of all-cause mortality (76), premature death (77), and the rate of 
cardiovascular disease (78) in the general population. Dose-response analyses have determined that the 
strongest health benefit accrues within the first 120 minutes per week of walking, further highlighting the 
potential impact of increasing PA among sedentary individuals (76). Moreover, given the widely accepted PA 
recommendations set forth by the American College of Sports Medicine (ACSM) (79) and by the International 
Organization of Physical Therapy in Mental Health (IOPTMH) (42), walking at a moderate-intensity level should 
be prioritized (See section C.3. for more details). 
A valuable way to facilitate the initial engagement of exercise and address the barriers of social 
isolation in individuals with SSDs is through group-based interventions, as they promote social interaction, 
camaraderie, and social support (36-39, 80). Group-based interventions also impact motivation by offering the 
opportunity to develop friendships centered around a common goal, thus satisfying relatedness and 
competence needs and promoting self-efficacy (35). Walking programs in the general population that promote 
social support also led to greater maintenance of behavior change (81, 82). Therefore, social support (and 
reduction of loneliness) may play a critical role in helping individuals with SSDs initiate and adhere to exercise 
programs (35). 
A critical component of goal setting and attainment is being able to monitor progress, which can be 
achieved via physical activity tracking devices. Pedometer use leads to an increase in PA – they are considered 
acceptable and are highly useful for setting PA goals (83-85), which helps to facilitate changes in exercise 
behavior (86). In fact, pedometers are the most cost-effective means of increasing PA in the general 
population (87). In a systematic review of 26 studies, pedometer use resulted in significant increases in PA 
(26.9% over baseline) (70). With recent advances in sensor and Bluetooth technologies, new physical activity 
monitors have emerged and are currently commercially available (e.g., Fitbit), which also allow the measuring 
of walking intensity (e.g., through heart rate; See Section C.3.). 
 

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The model above illustrates how our proposed intervention, (PACE-Life) will lead to increased exercise 
and improved outcomes. Specifically, PACE-Life includes five primary components: home-based walking, 
group-based walking, activity tracking, goal-setting, and if-then plans, four of which impact the SDT basic 
needs and one of which enhances autonomous motivation. Specifically, homebased walking targets autonomy 
needs (as individuals can do this independently), group-based walking targets relatedness needs, and activity 
tracking and goal setting target competence needs. Satisfaction of each of the SDT needs leads to the 
intermediate target of increased autonomous motivation. PACE-Life subjects also form if-then plans which 
serve to enhance the impact of autonomous motivation (66, 67) and promote actual exercise behavior (56, 
57). Engaging these intermediate targets in turn engenders the proximal outcomes of greater exercise 
participation (as measured by minutes spent walking per week and steps/day). Finally, increased exercise 
should lead to the improved primary outcome of CRF as well as improved secondary outcomes of loneliness, 
symptoms, resting heart rate, and systolic/diastolic blood pressure. 
The proposed research is highly innovative in at least three respects. First, the simplicity and 
practicality of PACE-life is a key innovation. As noted above, most previous interventions for individuals with 
SSDs required gym equipment (e.g., treadmills) as well as professional supervision to engage in exercise, thus 
limiting both sustainability and scalability (22-24, 26). The field demands pragmatic interventions that are low 
in resource costs and can be rapidly translated into clinical practice (48, 88). Our walking intervention is both 
cost-effective and highly accessible given that the group-based portion will be implemented in the vicinity of 
the outpatient clinic and the home-based portion will be completed at locations selected by subjects (e.g., 
outdoors on residential streets or indoors at malls during inclement weather). Additionally, the COVID-19 
pandemic has provided subjects an opportunity to participate in a virtual walking intervention. Though, 
technological inequities may serve as a barrier to overall feasibility outside of this intervention, providing 
subjects with technology (e.g., tablets and data plans) has further improved potential feasibility and scalability. 
Second, the focus on cardiorespiratory fitness (CRF) is novel. Although CRF has long been identified as 
a significant predictor of health, it has only recently received attention in exercise intervention research 
among individuals with SSDs. A meta-analysis on the effects of exercise on CRF in individuals with SSDs (12) 
revealed only 3 published randomized controlled trials that examined this health indicator (32, 89, 90). 
Vancampfort and colleagues (13) concluded that despite the few available studies on CRF in schizophrenia, 

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improvements in this domain are possible and may provide a “novel and valid exercise target that could lead 
to reductions in premature mortality in people with schizophrenia” (p. 456). In addition, we will measure CRF 
in a cost-effective and feasible manner without the need for expensive equipment, further displaying our 
commitment to scalability and sustainability. 
Third, the present research is conceptually innovative in targeting both motivation to exercise, and the 
effective translation of motivation into action. Previous interventions that focused merely on generating 
strong intentions to exercise have had little success (91) because the quality of motivation supporting these 
intentions was not addressed (92). PACE-Life is deliberately designed to engender high-quality (i.e., 
autonomous) motivation. However, even high-quality motivation may not equip people to deal effectively 
with problems that are inevitably encountered as they strive to exercise. These problems include failing to get 
started, becoming derailed by unwanted influences (e.g., distractions), and coping badly with unforeseen 
obstacles and lapses (51). If-then plans are an effective tool for dealing with each of these problems 
experienced by new exercisers (61, 93-95) and synergize the impact of autonomous motivation, helping to 
turn that motivation into action. 
 
2 
RESEARCH DESIGN AND METHODS 
2.1 OVERVIEW  
The project will consist of three primary phases: manual development, an open trial, and a small-scale 
RCT (See Table 1; Table 2 indicates updated project time based on the COVID-19 pandemic). These three 
phases will be iterative such that we will obtain and incorporate end-user feedback from clients and clinicians. 
Feedback from users will inform both the open trial and subsequently, the RCT.  
 
 
 
      Table 2: Project Timeline (COVID-19 Updated) 
 
 

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Rationale for clinic-based/home-based rather than a gym-based exercise intervention. We propose to 
provide PACE-life through a mental health clinic as individuals with SSDs usually have frequent contact with 
their providers. Furthermore, interventions that don’t require additional equipment or supervision by an 
exercise trainer have greater potential for integration into healthcare services for individuals with SSDs. Our 
rationale for a clinic-based versus a gym-based exercise program is also based upon recommendations for 
integrated medical care (104) as well as integrated physical activity within mental health services for this 
population (105). In addition to clinic-based sessions, we will include home-based sessions, which can be 
completed at any location and time of the subjects’ choosing to improve self-management and facilitate long-
term exercise adoption. The term, “home-based,” means only that individuals will be engaging in this 
component independently and do not need to attend a select location or require additional equipment. We 
will work with subjects to identify convenient walking routes using websites and apps (e.g. map my walk). 
Therefore, our intervention will include both clinic-based sessions and instructions for home-based sessions to 
prioritize feasibility and sustainability. Moreover, given the disruption of the COVID-19 pandemic, we’ve re-
designed our study to have feasibility in a virtual format. Subjects can participate in the study from their 
homes, as we provide them with technology (e.g., tablets and data plans) necessary for participating in virtual 
exercise sessions. Exercise sessions include dynamic, stationary exercises that model walking movements, to 
best match movements performed in outdoor walking sessions. These obstacles have provided the research 
team with an opportunity to learn about the sustainability and scalability of home-based virtual interventions, 
in addition to clinic-based interventions. 
Rationale for moderate-intensity walking as exercise modality. Walking is the primary form of exercise 
in PACE-life given its accessibility and association with meaningful fitness and health outcomes. PACE-life will 
combine walking groups and Fitbit with heart rate monitoring to encourage moderate-intensity walking in 
individuals with SSDs. The goal of PACE-life is to facilitate engagement in 150 min/week of moderate- intensity 
walking spread throughout the week, which is consistent with recommended fitness guidelines set forth by 
the ACSM (79) and by the IOPTMH (42). To achieve this goal, we will employ a stepwise approach of exercise 
participation to provide individual tailoring and reduce the likelihood of dropouts (103). Specific details and 
rationale of this approach are discussed below: 
Overview and rationale of stepwise approach. Stepwise approaches to exercise participation are often 
recommended for use with sedentary populations to reduce the risk of injury and dropouts (32, 103). 
Typically, these interventions will begin at low intensity and low frequency, and as individuals become more 
physically active, the intensity and frequency increase. This strategy is especially relevant to individuals with 
SSDs as they are quite sedentary and have little experience with consistent participation in exercise. 
Furthermore, individuals need to engage in moderate-intensity exercise, defined as exercising within 60-70% 
of heart rate reserve (HRR), in order to achieve meaningful changes in CRF (103). In sedentary individuals, 
moderate to high intensity exercise may not be achievable immediately in the first weeks of the program and 
starting physically deconditioned individuals in a program that is too intense can be physically dangerous and 
lead to significant dropouts (103, 106). As a result, a step-wise approach that begins at a lower-intensity and 
increases to moderate intensity is more appropriate and has been successfully implemented in SSDs (32, 89). 
For the present study, low and moderate intensity exercise will be operationalized by HRR (103, 106) where 
Low-intensity Exercise = 50-60% of HRR and Moderate-intensity exercise = 60-70% of HRR. 
We (Battaglini, PI) demonstrated the potential benefits of a step-wise exercise program in African-
American breast cancer survivors that began at a low intensity and later progressed to moderate intensity 
(107). The results showed a high completion rate (76%) and adherence to walking goals (70%). 

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2.2 SUBJECTS 
Based on the grave health concerns, physical inactivity, and growing urgent calls for action in 
individuals with psychotic disorders (116, 117), 56 study subjects will be recruited from various clinics in the 
Durham, Carrboro, Chapel Hill, and Raleigh area including, the UNC Schizophrenia Treatment and Evaluation 
Program (STEP) clinic in Raleigh and Carrboro, the Outreach and Support Intervention Services (OASIS) 
program in Chapel Hill, Carolina Behavioral Care, Club Nova, and Threshold. All subjects will have a primary 
diagnosis of a schizophrenia spectrum disorder. To obtain an estimate of IQ and to rule out any individuals 
with possible mental retardation, we will administer the WASI, which is comprised of Matrix Reasoning, 
Vocabulary, Similarities, and the Block Design subtests. During the COVID-19 pandemic, we will also administer 
the WRAT to test the reading level of participants. Additional demographic and clinical information that will be 
collected as self-report for possible use as covariates includes: 1) demographics: age, sex, ancestry, education, 
parent education; 2) health: smoking, substance use, current medications, duration of outpatient treatment, 
diet, physical activity, height, weight, BMI, and waist and hip circumference. 
 
2.2.1 INCLUSION CRITERIA 
1. DSM-V diagnosis of a Schizophrenia Spectrum Disorder (Schizophrenia, Schizoaffective Disorder, 
Brief Psychotic Disorder, Schizophreniform Disorder, and Unspecified Schizophrenia Spectrum and 
Other Psychotic Disorder)  
2. Age 18 or above, both genders, and any ancestry 
3. IQ>70; Reading Level > 4th Grade  
4. No hospitalizations in the last 3 months 
5. Clinically stable (no medication changes within the past month) 
6. Are not already engaging in consistent moderate-intensity exercise (cutoff = 60 min/week for the 
past 6 months)  
7. Present with no contra-indication to engage in regular moderate intensity exercise based on the 
ACSM guidelines (118). If individuals answer yes to one or more items on the of the PAR-Q, a 
questionnaire that assesses cardiovascular risk factors, she/he will require further evaluation by a 
physician prior to participating in the study 
8. Willing and able to provide informed consent. 
 
2.2.2 EXCLUSION CRITERIA  
1. Pregnant women will be excluded because pregnancy alters autonomic and immune 
responsiveness, increase weight gain, and can influence heart rate. 
 
3 
ASSESSMENT OF DATA 
At this stage of treatment development, specific outcomes include:  
1. Feasibility (Can PACE-life be delivered within this treatment setting?) 
• Will determine if recruitment procedures yield the target number of subjects in 3 months 
• Will determine feasibility of assessments based on subject compliance rates 
2. Tolerability (How well is PACE-life accepted by the subjects?) 

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• Will be evaluated by examining subject attendance to groups, adherence to homebased 
component of program, Fitbit usage, and dropout rates. 
3. Intervention adherence 
4. Evaluation of PACE-life. We will evaluate feasibility in two ways. First, we will determine if 
recruitment procedures yield the target number of subjects in 3 months. Second, we will determine 
feasibility of assessments based on subject compliance rates. The tolerability of PACE-life will be 
evaluated by examining subject attendance to groups, adherence to homebased component of 
program, Fitbit usage, and dropout rates. 
 
3.1  OUTCOMES 
The central hypothesis is that an intervention that increases physical activity as measured by minutes 
spent walking (at the prescribed intensity) and steps/day will result in improved health and lowered risk for 
premature mortality as evidenced by superior CRF (primary outcome), and on a variety of secondary outcomes 
(e.g. blood pressure). Guided by strong preliminary data and grounded in SDT, this hypothesis will be tested 
via three specific aims: 
1. To develop a manual-based walking intervention for individuals with SSDs: PACE-Life. The manual 
will include guidelines for goal setting and translating intentions into behaviors (i.e., “if-then” 
plans), instructions for the group-based walking activity and home-based walking activity (which 
includes Fitbits), and increasing exercise intensity in a step-wise manner.  
2. To examine the feasibility of implementing PACE-life at a community mental health clinic, and in a 
home-based virtual capacity, in a randomized controlled trial of 56 individuals with SSDs.  
3. We will also examine the impact of PACE-life on intermediate targets (autonomous motivation and 
SDT needs), proximal outcomes (minutes spent walking and steps/day), the primary outcome of 
CRF, and secondary outcomes. 
 
We hypothesize that PACE-life will be associated with:  
• Improved proximal and primary outcomes including greater minutes/week spent walking 
and steps/day and increased CRF at mid-treatment (3 months), post-test (6 months), and 
one-month follow-up;  
• Decreases in secondary outcomes including loneliness, SSD symptoms, resting heart rate, 
and blood pressure at mid-point, post-test, and one-month follow-up.  
• Higher levels of theoretically-relevant, intermediate targets (autonomous motivation and 
SDT needs) at mid-treatment, post-test, and one-month follow-up. 
 
4 
STUDY DESIGN 
During this phase of the trial, 56 subjects will be assigned to the fitbit only group (control) or the PACE-
Life walking group (intervention). The exercise intervention, PACE-Life, will last for 16 weeks and includes both 
group walks and independent walks (done at a location of the subject's choosing). Subjects will be asked to 
complete a total of 5 in-person, or virtual assessments at screening, baseline, mid-point, post-test, and 1-
month follow-up. 
 
4.1 INTERVENTION 

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Groups will occur twice per week, starting at 15-minute walking sessions, and increasing to 30 minutes 
sessions over the course of the intervention. The intensity, of both group walks and home-based walks will 
increase throughout this intervention in a stepwise fashion to create an exercise dose response to maximize 
impact on CRF. The rationale for this plan hinges on both the importance of maintaining cohesion and social 
interaction as well as the practicality concerns regarding sustainability. Furthermore, we tested a 2x/week 
group schedule in the pilot with high attendance rates and feedback (overall attendance: 84%). The overviews 
of in-person and virtual formats are given below: 
 
Weeks 
# of Clinic-based 
Group Sessions 
Duration of 
Group Sessions 
# of Home-
based Sessions 
Duration of Home-
based Sessions 
Intensity 
1-3 
2 
30 Minutes 
0 
30 Minutes 
50-60% of HRR 
4-6 
2 
30 Minutes 
0 
30 Minutes 
50-65% of HRR 
7-9 
2 
30 Minutes 
1 
30 Minutes 
60-65% of HRR 
10-12 
2 
30 Minutes 
1 
30 Minutes 
65-70% of HRR 
13-15 
2 
30 Minutes 
2 
30 Minutes 
65-70% of HRR 
16-18 
2 
30 Minutes 
2 
30 Minutes 
65-70% of HRR 
19-21 
2 
30 Minutes 
3 
30 Minutes 
70% of HRR 
22-24 
2 
30 Minutes 
3 
30 Minutes 
70% of HRR 
 
 
Week 
# of 
Virtual 
Group 
Sessions 
Links to Virtual Group Sessions 
Duration of 
Virtual Group 
Sessions 
# of 
Independent 
Walks 
Duration of 
Independent 
Sessions 
Intensity 
R
Pe
Ex
(
1 
2 
1st group: https://www.youtube.com/watch?v=cvrcgZ25MWw   
2nd group: https://www.youtube.com/watch?v=iBAjNQODSVo   
15 minutes 
0 
15 minutes 
50-60% of 
HRR 
1
2 
2 
1st group: https://www.youtube.com/watch?v=tW9IY48x1bc  
2nd group: https://www.youtube.com/watch?v=u08lo0bESJc  
15 minutes 
0 
15 minutes 
50-60% of 
HRR 
1
3 
2 
1st group: https://www.youtube.com/watch?v=wQrV75N2BrI     
2nd group: https://www.youtube.com/watch?v=-SSYX8sIOmM   
20 minutes 
1 
20 minutes 
50-65% of 
HRR 
1
4 
2 
1st group: https://www.youtube.com/watch?v=kqaNUjTR70A   
2nd group: https://www.youtube.com/watch?v=m9yI2LGZRE0    
20 minutes 
1 
20 minutes 
50-65% of 
HRR 
1
5 
2 
1st group: https://www.youtube.com/watch?v=kqaNUjTR70A   
2nd group: https://www.youtube.com/watch?v=UhpOl71brYI  
20 minutes 
1 
20 minutes 
60-65% of 
HRR 
1
6 
2 
1st group: https://www.youtube.com/watch?v=UXS_fFeGAlc   
2nd group: https://www.youtube.com/watch?v=0KPpICARPGQ   
20 minutes 
1 
20 minutes 
60-65% of 
HRR 
1
7 
2 
1st group: https://www.youtube.com/watch?v=_UabUNrjSE4  
2nd group: https://www.youtube.com/watch?v=GfiL9jPXMFE  
25 minutes 
2 
25 minutes 
60-65% of 
HRR 
1

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8 
2 
1st group: https://www.youtube.com/watch?v=v4YyCdTf9BM  
2nd group: https://www.youtube.com/watch?v=RImvimPo5u0    
25 minutes 
2 
25 minutes 
60-65% of 
HRR 
1
9 
2 
1st group: https://www.youtube.com/watch?v=hXhudyDRX8M   
2nd group: https://www.youtube.com/watch?v=baO6jTGmNFs  
25 minutes 
2 
25 minutes 
60-65% of 
HRR 
1
10 
2 
1st group: https://www.youtube.com/watch?v=RP0Q8geTcJc   
2nd group: https://www.youtube.com/watch?v=vUQXg5V7y2Q   
30 minutes 
2 
30 minutes 
60-65% of 
HRR 
1
11 
2 
1st group: https://www.youtube.com/watch?v=enYITYwvPAQ   
2nd group: https://www.youtube.com/watch?v=jf1Q8nep6JU  
30 minutes 
2 
30 minutes 
60-65% of 
HRR 
1
12 
2 
1st group: https://www.youtube.com/watch?v=p2ggHwtb-Zg   
2nd group: https://www.youtube.com/watch?v=R3AUw3-jtEo  
30 minutes 
2 
30 minutes 
60-65% of 
HRR 
1
13 
2 
1st group: https://www.youtube.com/watch?v=l5uilZNoaAU   
2nd group: https://www.youtube.com/watch?v=HSoDitXs35w  
30 minutes 
3 
30 minutes 
65-70% of 
HRR 
1
14 
2 
1st group: https://www.youtube.com/watch?v=kp67VFhbpsQ  
2nd group: https://www.youtube.com/watch?v=uUki7XMG0iA  
30 minutes 
3 
30 minutes 
65-70% of 
HRR 
1
15 
2 
1stgroup: https://www.youtube.com/watch?v=enYITYwvPAQ&list   
2nd group: https://www.youtube.com/watch?v=RP0Q8geTcJc   
30 minutes 
3 
30 minutes 
65-70% of 
HRR 
1
16 
2 
1st group: https://www.youtube.com/watch?v=p2ggHwtb-   
2nd group: https://www.youtube.com/watch?v=wwn3YJyOzdY      
30 minutes 
3 
30 minutes 
65-70% of 
HRR 
1
 
PACE-life will be integrated into the STEP outpatient clinics in Raleigh, NC and Carrboro, NC. The group 
walks will occur in the surrounding area around the clinics on sidewalks, bike trails, and residential streets. 
Goal setting groups and all assessments will take place in a conference room at the clinic. Virtual walking 
sessions will take place on the UNC HIPAA and Security-compliant Zoom video calls and can be completed at 
subjects’ homes. 
 
4.1.1 GOAL-SETTING 
Goal-setting will include setting goals for the upcoming week in terms of number of steps as well as 
how many intensity walks (at specified heart rate) that individuals plan to complete. Goal-setting materials 
draw upon SMART (specific, measurable, achievable, relevant, and time-based) principles as well as 
implementation intentions (i.e., if-then plans) and mental contrasting. Specifically, subjects will be asked to 
imagine what the best thing would be about walking/exercise more and then identify the biggest barriers. 
They will then be encouraged to create if-then plans about how to manage barriers to exercising more. This 
procedure has been extensively examined in social psychology research and has been shown to be successful 
in helping individuals increase their exercise (93). Goal-setting groups will be audiotaped and subsequently 
coded for fidelity to the protocol. 
 
4.1.2 FITBITS 
All subjects will be provided with a Fitbit that is labeled with a subject number. All Fitbits are paired to 
a Fitbit account with the username (pacelifeIDnumber@gmail.com) and password (pacelife; or 

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PacelifeIDnumber!). Data from Fitbit devices can be synced to the corresponding account and accessed 
through Fitbit.com. Subjects will be provided information about their accounts should they want to look at the 
data but will be asked not to change any of the settings as we will be using data for tracking steps/day and 
minutes spent walking. No identifying information will be inputted in the Fitbit.com account for subjects. 
 
4.1.3 Tablets & Data Plans 
All subjects assigned to the PACE-Life group will be given a tablet labeled with their subject number. If 
subjcets do not own a smartphone or personal computer, they may use the tablet for syncing their Fitbit 
devices. . The tablets will also be used to join virtual walking sessions. Subjects will be provided information 
about their devices but will be asked not to change any of the settings (or download new apps). No identifying 
information will be inputted in the subjects’ tablet. Additionally, subjects who do not have reliable wifi in their 
homes, will be given a monthly data plan to ensure proper connectivity throughout the study. 
 
4.2 STUDY PROCEDURES AND MEASUREMENTS 
4.2.1 SCREENING VISIT 
The following measures will be examined at screening:  
• Demographics- We will collect information on age, sex, ancestry, education, parent education, 
smoking, substance use, current medications, duration of outpatient treatment, and diet. 
• Intelligence- In adherence with our inclusion criteria that subjects must have an IQ greater than 
70, the Wechsler Abbreviated Scale of Intelligence (WASI) will be administered. Subjects 
participating during the COVID-19 pandemic must have a reading level above the 4th grade, the 
Wide Range Achievement Test (WRAT) will be administered. 
• Medical History- A licensed physician will complete the Medical History and Physical Exam 
Form. They will also complete a 10 minute physical to ensure health. Subjects participating 
during the COVID-19 pandemic will receive medical clearance from a General Practitioner (GP). 
Medical Clearance forms will be sent to and received from providers through the EPIC system. 
• Current Physical Activity- In order to ensure that subjects are healthy enough to begin the 
walking program, subjects will complete the Physical Activity Readiness Questionnaire (PAR-Q). 
• Diagnosis-The Mini International Neuropsychiatric Interview (MINI) will be utilized to assess 
symptoms. The MINI is a semi-structured interview that assesses for DSM diagnoses. The MINI 
will be used to verify that subjects have a schizophrenia spectrum diagnosis before they are 
enrolled in the study. Raters will be trained to conduct the MINI to a gold standard of reliability 
(i.e., intraclass correlation > .80). 
 
4.2.2  BASELINE, MID-POINT, POST-TEST, 1 MONTH FOLLOW-UP 
The following measures will be examined at the baseline, mid-point, post-test, and 1 month follow-up 
study visits: 
• Demographics- We will collect information on age, sex, ancestry, education, parent education, 
smoking, substance use, current medications, duration of outpatient treatment, and diet. 
• Minutes Spent Walking- We will utilize data recorded from Fitbits to assess minutes spent 
walking (by syncing Fitbits to corresponding Fitbit.com accounts and loading deidentified data 
onto study laptops).  

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• The Short Form International Physical Activity Questionnaire (IPAQ), a valid self-report 
measure, to assess changes in physical activity. The IPAQ Short Form is a four-item scale that 
assesses frequency and duration of walking, moderate-intensity exercise, vigorous-activity 
exercise, and sitting. 
• Steps/day. We will also collect daily step numbers using Fitbit data downloaded onto study 
laptops from Fitbit.com at group sessions. 
• Cardiorespiratory fitness (CRF)- CRF will be measured using the 6-minute walk test (6MWT) 
during which individuals are asked to walk continuously for six minutes on a flat, indoor surface 
around cones (separated by 100ft) and the primary outcome is the total distance walked. The 
6MWT is recommended for use with sedentary individuals and to evaluate the impact of an 
exercise intervention. Moreover, the 6MWT has been successfully administered to individuals 
with SSDs, including those in our pilot trial. As a result, we plan to utilize the 6MWT as our 
primary measure of CRF. Supplemental CRF measures will also be used. CRF will be calculated 
using an equation by Jackson, A. S., et al. 1990 (119) that includes recent weight and height for 
the calculation of BMI, gender, self-reported physical activity level, and age. Finally, participants 
will complete a Chair-Rise Task, where subjects will sit and stand from a chair for 30 seconds, 
and the 2-minute Step Test, where subjects will walk in place with their knees raising to hip-
height, to measure CRF. 
• Self-determination Basic Needs. The self-determination basic needs of autonomy, relatedness, 
and competence will be measured with two scales. The Basic Psychological Need Scale-in 
General is a self-report measure that assesses general satisfaction with autonomy, relatedness, 
and competence. Three subscale scores are produced. The Basic Psychological Needs in 
Exercise Scale (BPNES) is self-report scale that measures the extent to which basic needs are 
satisfied through exercise. 
• Symptoms- the Positive and Negative Syndrome Scale (PANSS) will be utilized to assess 
symptoms specifically present in schizophrenia spectrum disorders. The PANSS is a semi-
structured interview assessing positive symptoms, negative symptoms, and general 
psychopathology symptoms. Raters will be trained to conduct the PANSS to a gold standard of 
reliability (i.e., intraclass correlation > .80) 
• Resting Systolic/Diastolic Blood Pressure and RHR will be assessed following standardized 
procedures at the STEP clinic. Individuals with SSDs will be placed in a sitting position in a quiet 
room, with lights dimmed, and will be asked to remain quiet and relaxed with their eyes closed 
while avoiding movement for approximately 10 minutes. After 10 minutes, research team 
members will assess their RHR via palpation for 1 minute. Following the assessment of RHR, 
resting BP will be assessed using an automated blood pressure device following the 
manufacture standard procedures. Given the high rates of hypertension in this population, the 
assessments of blood pressure changes throughout this exercise intervention are significant 
indicators of potential benefits of exercise on improvements in physical health. Further, given 
the sedentary lifestyle of many individuals with SSD, changes in RHR upon the initiation of 
exercise is a valuable indicator of fitness and physical health. Due to COVID-19, all subjects 
completing virtual study visits will have these measures assessed at their homes, on UNC-CH 
campus (Fetzer Hall), or at the Wake STEP Clinic in Raleigh, NC. 

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• Autonomous Motivation- Given the available research indicating that autonomous motivation is 
related to negative symptoms and subsequent engagement, maintenance, and adoption of 
exercise in individuals with SSDs, we will measure this construct with The Behavioral Regulation 
in Exercise Questionnaire-2 (BREQ-2).  
• Enjoyment of Walking- Given that enjoyment of the walking program can impact adherence to 
the treatment, we will measure this construct with the Physical Activity Enjoyment Scale 
(PACES).  
• Planned Behavior- Available research has shown that intentions, self-efficacy, attitudes and 
norms are correlated to adherence in exercise. All items are derived from established measures 
of theory of planned behavior variables (e.g., Conner & Sparks, 2015). Responses are all on 7-
point scales. The order of items would be randomized.  
• Loneliness: The UCLA Loneliness Scale is a brief self-report measure that will be used to assess 
this construct.  
• Weight, BMI, and Waist/hip Circumference- We will measure weight, BMI, and waist/hip 
circumference at all assessments using the scale and measuring tape located at the STEP clinic.  
• Exit Surveys on PACE-life- At the conclusion of the open trial, we will administer a brief 
questionnaire to the subjects regarding satisfaction and acceptability that will have both forced 
choice and open-ended questions (End of Study Survey & CSQ-8). 
 
5 
 STATISTICAL ANALYSES 
5.1 DATA ANALYTIC PLAN 
Feasibility will be defined by our ability to meet our recruitment targets (56 people), frequency of 
engagement in the intervention by participants (group attendance and activity tracking/home-based 
adherence), and feedback on the intervention from participants. Feedback from participants will be 
incorporated into modifying the manual for the RCT and/or future interventions. 
Analyses of intermediate and primary outcomes will primarily be descriptive in nature. We will 
calculate means, standard deviations, and within-group effect sizes of intermediate targets (SDT needs and 
autonomous motivation), proximal outcomes, including minutes spent walking, and steps/day, the primary 
outcome of CRF, and the secondary outcomes including RHR, blood pressure, loneliness, and symptoms. 
Further, we will calculate the percentage of the sample meeting the threshold for clinically significant changes 
in our outcomes of 6MWT, steps/day, and minutes spent walking to determine whether these changes are 
clinically meaningful. Finally, we will explore the relationship between baseline IQ, treatment adherence and 
outcome improvement so as to determine if cognitive functioning is associated with treatment response. 
 
5.2 POWER ANALYSIS 
Power was estimated using Optimal Design Software.  Assuming n=56 (28 per group), alpha=05, and 
the covariate accounted for 50% of variance, the proposed study has reasonable power to detect an effect size 
of .50 or larger in comparison of the groups at the end of treatment or follow-up and of .75 or larger in 
comparisons of the size of change over time.  Thus, this study has good power to detect the types of 
differences detected in pilot study (ES of .50-1.03 in steps, .33-.40 in six-minute walk test, .54-.83 for BP and 
.52-1.09 for symptoms).   
 

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5.3 DATA MANAGEMENT 
All data will be entered by trained research assistants using REDCap software. Double data entry will 
be required for information not directly entered by the participants. Double data entry will also be entered by 
trained research assistants using REDCap software. All data analysis will be conducted by statistician, Oscar 
Gonzalez. 
 
 

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6 
RISKS AND BENEFITS 
There are some risks associated with the proposed research. First, collection of the clinical information 
may be associated with anxiety or embarrassment due to revealing personal information. Second, there is the 
risk that confidential personal information could be disclosed to others outside of the research staff. Third, 
there is risk in participating in the 6-minute walk test, Chair-Rise task, and 2-minute Step Test as a measure of 
cardiorespiratory fitness (CRF). Finally, there is risk associated with participating in the walking groups, such as 
ankle, leg, and back injuries, and cardiovascular distress. 
 
6.1 Monitoring Risks 
To address subject anxiety or embarrassment due to revealing person information, we have trained 
research staff who are experienced in working with individuals with schizophrenia spectrum disorders. They 
have been trained to put subjects at ease, let them take their time, and to conduct interviews in private 
rooms.  
To address the issue of accidental disclosure of personal information to others outside of the research 
staff, we will obtain a NIH Certificate of Confidentiality for the study. In addition, identifying research subjects 
by study number on all research documents minimizes the risk of breach of confidentiality. Study documents 
that must contain personal information, including the informed consent document, and the document that 
links study ID number to personal identifying information (necessary due to the longitudinal nature of the 
open trial and RCT) are kept in locked filing cabinets in locked rooms. Research data will be kept on password-
protected drives, and our computer systems are HIPAA compliant. All study staff participate in annual human 
subject training that includes education about responsibilities to minimize risk that confidentiality may be 
breached.  
To address the potential health risk associated with participation in the walking groups as well as the 6-
minute-walk-test, chair-rise task, and 2-minute step test, all subjects will obtain medical clearance from their 
general practitioner, or have a medical history and physical examination performed by Dr. Jarskog as part of 
the Screening procedures. Dr. Jarskog and/or a trained research assistant will also administer the PAR-Q, a 
widely used questionnaire to assess cardiovascular risk factors in advance of exercise initiation. For any 
subject who answers “yes” to one or more items on the PAR-Q, Dr. Jarskog and/or a trained research assistant 
will contact their PCP to discuss appropriateness for the subject to participate and help facilitate further 
evaluation as needed. In addition, the research staff will be trained by one of the PIs, Claudio Battaglini, an 
exercise physiologist, on the 6-minute-walk-test, chair-rise task, and 2-minute step test procedures. Further, if 
an individual shows any distress during this assessment, she or he will be instructed to stop the assessment 
and the research staff will contact Dr. Battaglini and Dr. Jarskog.  
To address the issue of physical injury or cardiovascular distress during the walking groups, the study 
clinicians will be trained by Dr. Battaglini on potential cardiovascular warning signs, and appropriate responses 
to any reported symptoms. Further, a safety plan for the walking groups will be developed prior to the 
initiation of the study with Drs. Battaglini and Jarskog, as well as the study clinicians. The walking groups will 
be conducted on level terrain, to minimize any potential leg, ankle or back injuries. Finally, it should be 
emphasized that this project is testing the impact of moderate-intensity walking, a less physically demanding 
and inherently safer activity when compared to other more rigorous activities that could pose greater 
cardiovascular and joint-related risks.  
Should any subject experience any problems during the study, our research team has trained staff that 
will be able to provide immediate care on-site. Subjects will be referred for additional care to the appropriate 

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providers on campus, such as Campus Health Services or the UNC Hospitals Emergency Department, if 
necessary. 
6.2 NON-SIGNIFICANT RISK DOCUMENTATION 
Pregnant women will be excluded because pregnancy alters autonomic and immune responsiveness, 
increase weight gain, and can influence heart rate. 
 
6.3 POTENTIAL BENEFITS OF THE RESEARCH TO SUBJECTS AND OTHERS 
The subjects who participate in the walking groups (in the open trial and RCT) may have a significant 
benefit on their cardiorespiratory fitness, which could have a subsequent impact on their overall physical and 
mental health. This study will provide currently unavailable information about the potential feasibility and 
effectiveness of a scalable and accessible exercise intervention for individuals with schizophrenia spectrum 
disorders. The risks of the study are minimal and reasonable in light of the knowledge gained. 
 
6.4 CONFIDENTIALITY OF DATA 
Risks regarding confidentiality will be minimized by using code numbers instead of names on study 
data. The code and the data will be stored in separate locked files at Davie or Howell Hall on UNC's campus. 
Similar subject records are scrutinized regularly and our procedure will add an extra level of protection 
because the research case numbers will be different from subject numbers (random numbers not associated 
with date of birth) and the code will be unavailable to anyone outside of the research team. Audio recordings 
of weekly group sessions will be saved on our secure lab server and on OneDrive so that offsite investigators 
may review and provide feedback to the clinicians conducting the sessions.  
Identifiable data will only be shared with the clinicians of subjects in the study with the permission of 
the subjects (obtained during informed consent). Clinicians will be contacted if issues arise related to safety 
during the trial. As part of the informed consent process, all subjects will provide the name and contact info of 
a clinician that we may contact if we become concerned about their safety (e.g., physical and/or mental 
health) during the course of the trial. We will not be sharing any confidential information with anybody 
outside of these clinicians. 
Identifiable data will be maintained for 5 years following study completion. At that point, hard copies 
of identifiable data including consent forms and contact information will be shredded. Electronic data will be 
de-identified upon entry, with the exception of the subjects' birth dates for the purposes of calculating their 
exact age. 
 
7 
DATA SAFETY AND MONITORING PLAN 
7.1 ADVERSE EVENTS 
Dr. Jarskog (Co-I) will function as the Project Medical Officer and will be available on pager and cell 
phone to all co-investigators to discuss any safety issue that emerges over the course of the study. All adverse 
events (AEs) occurring during the course of the study will be documented and reported to Dr. Jarskog. All 
Serious Adverse Events (SAEs) will also be reported to the IRB and NIMH. The occurrence of AEs will be 
assessed during the study and the investigators will follow all AEs to the point of satisfactory resolution. An 
independent physician will serve as Medical Monitor (Dr. Karen Graham, from the Department of Psychiatry). 
AEs will be tracked over the course of the study and will be reported at the midpoint and endpoint of each 
walking group cohort to the DSC. All SAEs will be reported to the DSC within 24 hours of learning of the event. 

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7.2 SERIOUS ADVERSE EVENTS 
AEs will be assessed to determine if they meet criteria for a SAE. SAEs, as defined by the FDA, will be 
systematically evaluated at each clinic visit. Any SAE will be reported to the IRB and NIMH. The initial SAE 
report will be followed by submission of a completed SAE report to each institution. In the event that a subject 
either withdraws from the study or the investigator decides to discontinue a subject due to SAE, the subject 
will have appropriate follow-up and/or stabilization. Follow-up will continue until the problem requiring 
hospitalization has resolved or stabilized with no further change expected, is clearly unrelated to study 
procedures, or results in death. Outcome of SAEs will be periodically reported to NIMH. A summary of the 
SAEs that occurred during the previous year will be included in the annual progress report to NIMH.  
The trial period is defined from the time that the informed consent document is signed until 30 days 
after the last study visit. All serious AE’s occurring during the trial period (including death due to any cause) or 
within 30 days after the last study visit will be communicated within 1 day of the investigator becoming aware 
of the event to designated personnel, using the telephone or fax numbers provided in the Study Reference 
Manual. Any fatal or life-threatening AE’s will be reported immediately, but no longer than 1 day from the 
time the investigator becomes aware of the event. A causality assessment will be provided for all SAEs. Critical 
follow-up information on SAEs will be provided as soon as it is available, but no longer than 1 day from the 
time the investigator became aware of the information. Other essential, but not critical, information may be 
reported within the following 5 days. An SAE, as defined by the FDA for use in clinical trials 
https://www.fda.gov/safety/medwatch/howtoreport/ucm053087.htm), is an adverse event that satisfies any 
of the following criteria: 
• Results in death. 
• Is immediately life-threatening, including potentially life threatening suicidal behavior or 
suicidal behavior that results in hospitalization. 
• Requires inpatient hospitalization or prolongation of existing hospitalization. 
• Results in persistent or significant disability or incapacity. 
• Is a congenital abnormality or birth defect. 
• Is an important medical event that may jeopardize the subject or may require medical 
intervention to prevent one of the outcomes listed above. Examples would include allergic 
bronchospasm that requires treatment in an emergency department, or a seizure that does not 
result in hospitalization. 
The causality of SAEs (i.e., their degree of relatedness to study treatment) will be assessed by the 
investigators. 
 
7.3 DEATH 
All deaths occurring within the trial period or within 30 days after the last day that the study 
intervention is administered will be reported within 1 day of the investigator becoming aware of the event. If 
an autopsy has been performed, results of the autopsy will be obtained and forwarded along with any 
available toxicology reports. 
 
7.4 PREGNANCY 

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Pregnancy is an exclusion criterion and women who can become pregnant should use adequate 
methods of birth control as outlined in the inclusion criteria. Should a pregnancy occur it must be reported in 
accordance with the procedures described below. Pregnancy in itself is not regarded as an AE unless there is a 
suspicion that an intervention may have interfered with the effectiveness of a contraceptive medication. 
However, the outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth or 
congenital abnormality) must be followed up and documented even if the subject was discontinued from the 
study. The Adverse Events/Side Affects form will be used for this purpose. All reports of congenital 
abnormalities/birth defects are SAE’s. Spontaneous miscarriages should also be reported and handled as 
SAE’s. All other outcomes of pregnancy must be reported on the Adverse Events/Side Effects form. 
 
8 
RECRUITMENT STRATEGY 
 
Subjects will be recruited from various clinics in  Durham, Carrboro, Chapel Hill, and Raleigh, North 
Carolina. Clinics and sites include the UNC Schizophrenia Treatment and Evaluation Program (STEP) clinics in 
Raleigh and Carrboro, the Outreach and Support Intervention Services (OASIS) program in Chapel Hill, Carolina 
Behavioral Care, Club Nova, and Threshold.. STEP, in particular, provides services to approximately 435 clients 
annually; 76% at STEP meet criteria for schizophrenia spectrum disorders (SSD). Clients will be approached 
about the study in a manner similar to what would happen in the real world outside of a research study. 
Specifically, psychiatrists, clinicians, and nurses will provide information to clients during appointments, 
groups, and in the clinic waiting area of a potential new exercise group. If the client is interested, then the 
research assistant will be notified to get in contact with the interested client. IRB approved flyers will also be 
posted at STEP. 
 
We will supplement recruitment at STEP Wake, as needed, with assistance from the North Carolina 
Psychiatric Research Center (NCPRC) and STEP-Chapel Hill. Jarskog (Co-I) is the research director of the NCPRC. 
The NCPRC is co-located with the STEP clinic in Raleigh and has dedicated staff and space dedicated to 
outpatient research. The NCPRC is an outpatient research facility that is integrated into the UNC STEP Clinic of 
Wake County. The mission of the NCPRC is to study the pathophysiology of and advance treatments for 
schizophrenia and related disorders. Research conducted at the NCPRC is currently funded by the NIMH, 
NIDDK, foundations that support mental health research, and selective collaborations with the pharmaceutical 
industry. The NCPRC fosters active collaborative research both within and across departments at UNC-Chapel 
Hill and with other academic institutions. It also serves as a core facility where other investigators at UNC-
Chapel Hill can conduct mental health-related research. STEP-Chapel Hill has 944 active clients. Over 75% have 
a psychotic disorder and approximately 56% are female. Finally, we will recruit individuals who have agreed to 
be contacted about future studies while they were subjects in past research studies conducted by Penn (~300 
individuals with SSDs). 
 
9 
CONSENT PROCESS 
Research staff will obtain informed consent directly from each subject. Staff obtaining the consent will provide 
the subject with a written document explaining the testing procedures and risks, and will answer any 
questions. We have several procedures in place to ensure that prospective participants fully understand the 
procedures, risks, and protections of the study. First, the consent form is written in easy to understand 
language. Second, the researcher reads the form to and with the potential subject, and invites questions after 
each section of the form. Third, the researcher asks the subject a series of questions about the study, such as 

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what they are to do if they no longer want to participate, or what they would do if they experience any stress 
during the protocol (this is to be used as comprehension check before signing). Potential subjects also had the 
option of providing informed consent verbally, to limit their exposure to the COVID-19 virus. In the virtual 
setting, subjects were provided an electronic copy of the consent form and followed along while the 
researcher reads the form to and with the potential subject, inviting questions after each section of the form. 
The same comprehension checks were used in the virtual setting. 
 
 

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