Exercise as an Adjuvant Therapy for Veterans With PTSD
Phase: NA
Conditions: Post-traumatic
Sponsor: VA Office of Research and Development

Research Protocol: Exercise as an Adjuvant Therapy for Veterans with PTSD
NCT02295995
Document date: 8.6.19
Principal Investigator: Katherine S. Hall, Ph.D.
Physical Activity and PTSD, Hall, version 10 dated 8/6/19
1

Posttraumatic Stress Disorder (PTSD) is a common psychological condition in Veterans. 
The prevalence of PTSD is highest among Veterans age 65 and older, with an estimated 
31% of older Veterans reporting PTSD symptoms. Many of these older Veterans have 
endured 35-50 years with chronic PTSD symptoms, and have a host of physical and 
psychological health problems.1-3 Over time, these symptoms can contribute to increased 
health risk and greater disability. My own work from the CDA-1 (RR&D E7822M) period 
provides compelling evidence of accelerated functional decline in Veterans with PTSD 
characterized by impaired mobility, severe cardiovascular deconditioning, and muscle 
weakness.4 This all translates into a significant economic and logistical burden on the VA 
health care system. 
Exercise training is an established intervention that holds great promise as an adjunctive 
therapy for PTSD. Clinical practice guidelines mention exercise as a potential approach 
for managing PTSD symptoms, with the caveat that there is insufficient evidence 
regarding exercise therapy for PTSD.5 Given the potential impact of exercise to improve 
both PTSD symptoms and physical comorbidities, there is compelling need for an 
evidence-based approach to prescribing exercise for patients with PTSD. To our 
knowledge, studies of exercise and PTSD have been limited to observational, or single-
arm studies, and have not been directed at older Veterans. This study would be the first 
randomized clinical trial of exercise for PTSD.
Despite the strong evidence for exercise in promoting physical and psychological well-
being, the majority of Veterans with PTSD are physically inactive. A recent study of 
over 500,000 older Veterans reported that compared to Veterans with other psychiatric
diagnoses, rates of physical inactivity were highest among Veterans with PTSD, with 
67.5% reporting no regular activity. 6
The goal of the current study is to evaluate the efficacy and feasibility of a tailored 
supervised physical activity program for older Veterans with PTSD. Proposed is a 
feasibility trial with a two-group design in which older Veterans (60 years and older) with 
PTSD followed by the VA will be screened and 80 will be randomized to either:
PHYSICAL ACTIVITY TRAINING (PA), a 12-week supervised physical activity 
program that combines guideline-based exercise prescription with individual 
progression/tailoring, and utilizes social cognitive tools (e.g., goal setting, 
troubleshooting barriers) to promote initiation and maintenance.
VA USUAL CARE-WAIT LIST CONTROL (UC), which includes all elements of care
associated with enrollment in the VA healthcare system. Upon completion of the 
initial 12 weeks, patients will be offered enrollment in the 12-week supervised 
activity training portion of the study or a home-based exercise prescription.
Veterans with PTSD face physical (particularly pain and disability) and psychological 
(depressed mood/lack of motivation, avoidance of social activities) barriers that are 
known to hinder physical activity. 7' 8' 9' 17' 18 Therefore Veterans with PTSD need specific 
guidance on appropriate, graded exercise that accounts for these limitations. These 
Physical Activity and PTSD, Hall, version 10 dated 8/6/19
2

barriers are all addressed by the proposed exercise intervention. If physical activity 
promotion programs are to have a significant impact on changing health behavior, we 
must identify new and innovative strategies to increase treatment access and 
participation among vulnerable populations, including those with psychological 
conditions such as PTSD. Specific aims are to:
AIM 1: Determine the feasibility, fidelity and acceptability of a pilot study that consists of
random assignment to Physical Activity or Usual Care. This includes feasibility 
assessment of screening and recruitment; fidelity to the intervention assessed by 
adherence and retention; and acceptability assessed by attrition, patient satisfaction and 
provider acceptability questionnaires.
AIM 2: Determine the effect sizes for planned future studies of physical activity, with 
PTSD symptoms and
physical function as primary outcomes of interest. Of secondary interest are: pain, 
sleep, psychological well-being, and durability of effects.
The funding source for the study is a VA Rehabilitation Research and Development 
Career Development Award awarded to Dr. Katherine Hall. Portions of the salaries of 
Dr. Hall's study team will be funded by this grant.
METHODS
Participants
We anticipate consenting and screening 110 older Veterans with PTSD in order to reach 
our goal of randomizing 80 participants. Based on the following conservative 
assumptions, we expect to be able to recruit approximately 120 Veterans in the 36-
month enrollment period; we anticipate more than 15 screen outs at the screening visit. 
There are currently over 3,500 Veterans receiving care for PTSD in the Durham VAMC 
PTSD clinic, and approximately 15% of these Veterans are over the age of 60. If we only 
enroll 10% of eligible Veterans, we expect to achieve our recruitment goal of 80 eligible 
Veterans within a 36 months recruitment window. Based on our previous studies of older 
Veterans, we expect that 10-15% of our participants will be female, and 40% will be 
minorities. See Table 1 for a summary of the study's inclusion and exclusion criteria.
Table 1. Inclusion/Exclusion Criteria
Veterans must meet all inclusion 
criteria:
Veterans who meet any one of the exclusion criteria will be 
excluded:
Physical Activity and PTSD, Hall, version 10 dated 8/6/19
3

60-89 years of age
Live within 50 miles of the Durham
VAMC and have reliable 
transportation to exercise facility
Registered for care at the Durham 
VAMC
Independently mobile (assistive 
devices acceptable)
Meet DSM-5 criteria for current 
PTSD
Exercising less than 30 
minutes/day on less than 5 
days/week
Free of cognitive impairments as 
measured by the Short Portable 
Mental Status Questionnaire or a 
diagnosis of Alzheimer’s Disease
Speak and write fluent 
conversational English
Active substance abuse or dependence other than nicotine 
(they will need to be abstinent for six months, i.e., in early 
remission)
Cognitive impairment (inability to complete study 
measures)
Current diagnosis of psychotic or bipolar disorder
Clinical history of CVD occurring within the past 3 months 
(angina, ventricular tachycardia, COPD with 2 or more 
hospitalizations within the past year and/or on oxygen, and 
stroke with moderate to severe aphasia)
Uncontrolled hypertension (diastolic BP > 110 mmHg or 
systolic BP >200 mmHg on medications at rest)
Renal disease or currently receiving dialysis
Non-recommended for supervised exercise by HCP
Proliferative retinopathy
Currently receiving trauma-focused therapy
Psychotropic medication initiation within 6 weeks prior to 
phone screen (excluded participants may be reconsidered 
for eligibility once medication stability has been achieved)
Lack of interest in exercising or unwilling to be randomized
Physical Activity and PTSD, Hall, version 10 dated 8/6/19
4

Recruitment
Study staff will identify potential eligible Veterans using several different means. First, 
potentially eligible Veterans will be identified from the Traumatic Stress and Health 
Laboratory's "Contact Database," IRB #1080, directed by Dr. Jean Beckham. This 
database contains information about previous study participants who have agreed to be 
contacted about other studies for which they may qualify. Second, a list of potential 
veteran participants with PTSD will be obtained using the VA's DART system. Third, flyers
that have been approved by Durham VAMC's Institutional Review Board (IRB) will be 
posted on research bulletin boards, program offices, and clinic areas. Fourth, VA 
clinicians may refer potential participants by obtaining their permission to forward their 
contact information to study staff.
For those Veterans identified through the Contact Database or the DART system, a 
review of their medical history (via CPRS) will first be conducted for every potential 
participant to assess initial eligibility (see exclusion criteria above). Potential participants
identified from this database or DART will then be sent an introductory letter signed by 
the Pl that describes the study and informs them that they will be called regarding 
participation .. In the letter, potential participants will be given an "opt-out" number to 
call in order to decline participation and/or further contact regarding participation. Seven
business days after the mailing, Veterans who have not called the study number to 
decline participation will be called by a study staff member to request their participation 
in the research study (see telephone screen script). In the telephone contact, the study 
staff member will inform the Veteran that he/she was selected for recruitment because 
he/she is an older Veteran with PTSD who previously expressed interest in other research
studies at the Durham VAMC and is registered for care at Durham VAMC (Contact 
database participants only).
Any Veteran who contacts or is contacted by study staff will be told that their 
participation is voluntary, and they may choose not to answer any questions that they 
find too sensitive. Also, Veterans will be told that their participation will not affect their 
care at the VA. The study staff member will explain the study in detail, including 
compensation. No study procedures will begin until formal, written informed consent has 
been obtained.
Study Procedures
Table 2 depicts a summary of study procedures for control group participants; Table 3 
depicts a summary of study procedures for PA group participants.
Table 2. Usual Care Group Study Procedures
Session
Tasks
Time
Payment
Screening (Phone)
    Screening assessments
15 min
None
1 (lab)
    Consent and complete screening
    Baseline questionnaires
    Height, weight, blood pressure
    Physical performance tests & 
activity monitor
30 min
2.5 to 3 
hours
$50
Week 12 (lab; end 
of wait-list study 
    Questionnaires
    Height, weight, blood pressure 
2.5 to 3 
hours
$75
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
5

period)
    Physical performance tests & 
activity monitor
    First day of supervised exercise or 
home-based exercise prescription
TOTAL
Up to $125
Table 3. PA Group Study Procedures
Session
Tasks
Time
Payment
Screening 
(Phone)
    Screening assessments
15 min
None
1 (lab)
    Consent and complete screening
    Baseline questionnaires
    Height, weight, blood pressure
    Physical performance tests & activity 
monitor
    Set start date for exercise
30 min
2.5 to 3 
hours
$50
Week 12 
(lab; end of 
study 
period)
    Questionnaires
    Height, weight, blood pressure 
    Physical performance tests & activity 
monitor
    Last day of study exercise
    Home-based exercise prescription or 
Gerofit referral
2.5 to 3 
hours
$75
1 year post 
exercise 
(mail) 

ACLS Questionnaire, Mobile use survey 

Activity Monitor
45 minutes 
to 1 hour
$25
TOTAL
Up to 
$150
Telephone Screening. All potential participants will complete an initial telephone 
screening to determine eligibility. A researcher will explain the study in detail and lead 
the eligible participant through answering the screening assessments (see Table 4). 
Since current PTSD is an inclusion criterion, the Primary Care PTSD Screen (PC-PTSD) will 
be administered as an initial screen for presence of PTSD symptoms. Because substance 
abuse or dependence, not any drug use, is an exclusion criterion for this study, exclusion
will be based on interview results using the three-item AUDIT-C (≥4 for men; ≥3 for 
women)10 and ten-item DAST-10 (≥3).11
Baseline and Follow-Up. During the first lab appointment, informed consent with 
HIPAA authorization will be obtained, a final screening measure will be administered 
(CAPS -5),and a questionnaire battery and physical performance assessments will be 
completed (see Table 4). 
At this first session, eligible participants will be randomized to one of the two treatment 
groups. Any Veteran who is randomized to the UC wait-list control condition will be told 
that he/she will be scheduled for a 12-week follow-up session, and that they may be 
contacted prior to this follow-up session for a brief check-in by study staff to inquire 
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
6

about any adverse events that may have occurred, as well as changes they may have 
made in medications or mental health therapy. At the end of this initial 12 weeks, 
patients in the UC wait-list control condition will be enrolled in the supervised exercise 
program for an additional 12 weeks. All Veterans will be given the results of their 
physical performance tests and activity monitor (average daily steps) along with a home-
based exercise prescription once the study is completed. For those Veterans aged ≥65 
years, they will be offered a referral to the Durham VAMC Gerofit program. 
As a sub-study of this larger protocol, we are also interested in learning more about 
technology access and use of VA apps in this population. This information will be 
particularly useful to inform future exercise interventions for older veterans that utilize 
technology to extend reach.  All participants who completed the study protocol (UC + 
PA) will be eligible for this sub-study and will be contacted.  Study participants will be 
sent a letter in the mail signed by the PI describing what this inquiry entails (see letter). 
In the letter, potential participants will be given an "opt-out" number to call in order to 
decline participation and/or further contact. Seven business days after the mailing, 
Veterans who have not called the study number to decline participation will be called to 
request their participation in the mobile device questionnaire (see telephone script). 
Phone contact will cease after 3 attempted (and unanswered) phone calls. The CRC will 
not contact anyone who withdrew their consent.  Only Veterans who have completed the
exercise program will be queried about if/how they use technology to track their health 
via 8 questions (see attached telephone script).  Once contact is made, participants will 
be asked if they have a mobile device—and if so what type and if they have access to 
the internet on their devices.  In addition, they will be asked how often they use the 
internet and their mobile apps per week and day.  Specifically, the questions will ask 
about the VA PTSD coach app, fitness trackers and monitors, and if Veterans connect 
these devices to their computer.  Responses to the telephone survey will be recorded on 
a paper copy by the CRC and entered in a VA REDCap database.  
Table 4. Timeline of Study Assessments
Session:
Assessment:
Pre-
screening
Week 1
Screening
(Telephone)
Week 1
Baseline 
Week 12
1 year 
Medical History (CPRS 
review)
X
Primary Care PTSD Screen 
X
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
7

(PC-PTSD)
Alcohol consumption: AUDIT-
C10
X
Drug use: DAST-1011
X
Demographics
X
Short Portable Mental Status 
Questionnaire (SPMSQ)19
X
Clinician-Administered PTSD 
Scale for DSM-5 (CAPS-5)12
X
PTSD Checklist for DSM-5 
(PCL-5)13
X
X-Pt. 3 
only
State Trait Anxiety Inventory 
–TRAIT34
X
X
Mental Health Service 
Utilization
X
X
Physical activity: ACLS29
X
X
X
Comorbidity 
X
X
Medical Outcomes Study (SF-
36)15
X
X
Depression Severity (PHQ-
9)35
X
X
Memory (FOF)33
X
X
Sleep: PSQI + PSQIA PTSD 
Addendum16
X
X
Nutrition
X
X
Biometric data
X
X
Physical performance tests:
…Single-Leg Stance
   10-Meter Walk
   30-Sec Chair Stand
   8 Foot Up-and-Go Test20
   6MWT21
X
X
ActiGraph activity monitor
X
X
X
Program Evaluation
X
Mobile device use telephone 
survey 
X 
Any Veteran who is randomized to the PA group will be offered a 12-week supervised 
exercise program. PA group participants will receive a personalized exercise prescription 
based on their exercise history and current health status as well as training in the proper
use of exercise equipment. The exercise protocol consists of a 5-10 minute warm-up, 
followed by a series of progressive strengthening and aerobic exercises, and ending with
a 5-10 minute cool-down. Walking will be the primary mode of aerobic exercise, the 
duration and intensity of which will be gradually increased over the course of the trial 
(see Table 5).
As this is expected to be a largely sedentary population, exercises will be introduced in a
staged manner in order to maximize adherence and technique acquisition. Personalized 
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
8

programs may include a selection of 8 to 12 of the muscle-strengthening exercises 
identified, will target major muscle groups as well as primary joints, and will include 1-3 
sets of 8-12 repetitions for each exercise (see Table 5). The major muscle groups include
chest (pectoral), shoulders (deltoids, rotator cuff, scapular stabilizers, trapezius), arms 
(biceps, triceps, forearm group), back (latissimus dorsi, erector spinae), abdomen (rectus
abdominus, obliques, transverse abdominus, intercostals), and legs (gluteals, 
quadriceps, hamstrings, gastrocnemius). The primary joints include the knees, hips, and 
shoulders. A rest period of 2-3 min between sets of the same exercise will be 
programmed. Modalities may include body weight, free weights, cables and exercise 
bands. The amount of resistance will be determined by choosing a weight that can be 
moved the desired number of repetitions before it becomes too heavy. Participants will 
be encouraged to progress the resistance on at least a monthly basis, as tolerated. Once
exercise technique is considered competent by our staff, participants will be advised to 
perform the exercises in a circuit-like manner. Participants will be encouraged to 
complete these strengthening exercises on 3 days/week. The duration of each exercise 
session is expected to last 45-60 minutes.
Table 5. Example Exercises and Progression of Intensity
Resistance 
Exercises
Level 1
Level 2
Level 3
Leg press/Squats
Seated leg press
(single leg)
Sit-to-stand
Squats
Bent over row or 
seated row
1-2 sets, 8-12 reps*
2 sets
Increase reps/wt as
tolerated
Leg extensions
1-2 sets, 8-12 reps,
BW
2 sets
Increase reps/wt as
tolerated
Chest press
1-2 sets, 8-12 reps 
2 sets
Increase reps/wt as
tolerated
Triceps kickback
1-2 sets, 8-12 reps
2 sets
Increase reps/wt as
tolerated
Lat Pull down
1-2 sets, 8-12 reps
2 sets
Increase reps/wt as
tolerated
Oblique side bend
1-2 sets, 8-12 reps,
BW
Light DB
Increase reps/wt as
tolerated
Lateral raise
1-2 sets, 8-12 reps
Increase reps as
tolerated
Increase reps/wt as
tolerated
Hip abduction
1-2 sets, 8-12 reps
BW
Increase reps as
tolerated
Increase reps/wt as
tolerated
Internal/External 
shoulder rotation
1-2 sets, 8-12 reps
with EB
Cable or light DB
Increase reps/wt as
tolerated
Bird-dog (core)
1-2 sets, 8-12 reps
3 sets
Increase reps
Rear delt raise
1-2 sets, 8-12 reps
Increase weight as
tolerated
Increase reps/wt as
tolerated
Aerobic Exercise
Week 1
Week 2
Week 3
Week 4
Week 5
Week
6+
Walking duration 
(min)
5-10 min
15
20-25
25-30
30
30
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
9

Walking intensity 
(RPE)
3
3
3
3
3
4-7
EB = Exercise Band 
DB =
Dumbbel
l
BW = Body Weight
The American College of Sports Medicine recommends that activity intensity for older 
adults should be defined relative to an individual's fitness within the context of 
perceived physical exertion. As such, initial program intensity will be set using a 10-point
scale, on which 0 ="no exertion at all/sitting" and 10 ="maximal effort." Participants will 
be instructed to exercise between 3 (light to moderate) and 7 (moderate to hard); these 
levels will be reinforced by advising participants to exercise at a level that is close to 
their "conversational limit" (i.e., "talk test"), which is associated with more labored 
breathing. This method of specifying intensity is easily understood, can be readily 
applied to individual activities, and will increase as an individual's fitness level improves.
Individual limitations such as musculoskeletal conditions and balance will also be 
considered when prescribing the exercises.
Individuals who report pre-exercise resting systolic blood pressure> 200 mmHg or 
diastolic blood pressure> 110 mmHg will be asked to refrain from exercise for the day. 
Individuals who develop the following signs or symptoms during the exercise session will 
be asked to terminate their exercise session for that day and will be referred to their 
health care provider: moderate to severe angina, ataxia, dizziness or near syncope, or 
signs of poor perfusion such as cyanosis or pallor. As this supervised exercise program is 
held in a private fitness facility off-site from the Durham VAMC, in the event of 
emergency, emergency services (9-1-1) will be called.
Objective assessment of physical activity and sleep will be assessed at baseline and 12 
weeks with the ActiGraph GT3X activity monitor (accelerometer). This monitor has been 
extensively validated in clinical populations to collect physical activity behavior and 
sleep quality and quantity. Accelerometers, small devices which measure intensity of 
acceleration, have the ability to quantify the intensity, duration, and frequency of 
activity. The accelerometer is a lightweight device (45 g) that is equivalent in size to a 
pedometer. Accelerometers such as the ActiGraph are programmed to detect body 
movement and reject other forms of movement (such as vibration). The acceleration 
signal is digitally converted, resulting in a numerical value of "activity counts" per time 
interval. On their own, raw activity counts are uninterpretable, and can only be accessed
using Actilife software. Upon download with the Actilife software, these activity counts 
can then be translated into estimates of energy expenditure using activity-count cut 
points which have been developed to characterize activity intensity levels. In addition to 
quantifying time spent in various intensity levels the ActiGraph also assesses sleep 
activity, which can be scored according to sleep onset, sleep latency, amount of sleep, 
and sleep efficiency.
Participant Reimbursement. As described in Tables 2 and 3 above, study participants 
in the PA Arm may receive up to $150 for full participation in the study, while 
participants in the UC wait-list control arm may receive up to $125 for full participation in
the study. In our previous studies, the follow-up rates for assessments have been 
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
10

approximately 85%. We have added an incremental incentive structure ($50 for baseline 
and $75 for 12-week assessments) for each subsequent time point to encourage follow-
up assessment completion. Payment for participation will be by direct deposit issued by 
VA Financial Services. 
Consumer and Expert Advisory Board. We will convene a Consumer and Expert 
Advisory Board comprised of Veteran consumers and expert clinician provider(s). The 
Advisory Board will meet annually with the research team to review the research 
project. In addition, the Advisory Board will provide guidance and technical assistance to
the project. In year 1, the board will review the proposed study measures and the study 
procedures and provide an external perspective; advising the research team about 
issues of importance to Veterans with PTSD. In years 2 and 3, the implementation 
progress of the study will be reviewed by the board, and the board members will be 
specifically queried for input regarding any obstacles in regard to recruitment and 
retention. In year 4 the board will advise the research team regarding dissemination 
issues including suggestions for specific venues, and translating scientific langue to 
consumer language.
Participant photographs/videos. Study participants may occasionally be asked to 
let us photograph/video record them doing their exercises, for use in potential future 
professional presentations and/or promotional materials. This is certainly voluntary on 
the part of the participant, and written authorization (VA Form 10-3203 CONSENT FOR 
USE OF PICTURE AND/OR VOICE) from the participants will be obtained prior to any 
photography/video. These forms will be stored in the secured study cabinet located in 
the research coordinator's office. All recordings will be done using Samsung HMX-W300 
or Toshiba Camileo x200 Full HD Camcorder. Verbal consent will be obtained from the 
participant at the start of the recording by saying "the video tape is running, can you 
please affirm that you are ok with being recorded." The digital photo and video files will 
be transferred to the VA computer via a VA-issued encrypted thumb drive (issued to Dr. 
Hall). All media files will be encrypted and stored on the secure directory 
(S:\Research\Hall_Physical Activity Research\Participant Records).
RISK/BENEFIT ASSESSMENT
The clinical interview to establish diagnosis can cause some psychological distress in the
form of a temporary increase in anxiety, but any ensuing distress is usually well 
tolerated. There are no known psychological hazards or risks associated with completing 
questionnaires. If during the study any information reveals suicidal intent, depression, or 
other major clinical findings, the participant's primary physician will be notified. In 
addition, if an individual reveals current intent to harm him/herself or someone else, we 
will escort (or have escorted) the patient to the hospital's emergency room to be seen by
staff in the Psychiatric Emergency Clinic (PEC). In the event this information is revealed 
over the phone, we will transfer this person directly to the Veterans Crisis Line.
The physical performance tests include activities such as walking, standing, stepping, 
and stretching. These activities reflect common activities of daily living and as such, are 
associated with minimal risk for injury. However, there is a small risk of falls or muscle 
soreness with physical testing. To minimize risk, trained study personnel will oversee 
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
11

physical performance testing at all times. The risk of doing moderate exercise is low, 
and may be associated with risk of injury, falls, fainting, dizziness, or muscle soreness. 
There is even the risk of sudden death or stroke. To minimize these risks during exercise,
participants will be instructed to exercise at a comfortable level and to never push 
themselves to a point beyond where they feel safe. Participants will also be monitored 
and instructed to report symptoms such as unusual shortness of breath, dizziness, 
tightness or pain in the chest or arms, skipping heart beats, numbness, loss of balance, 
nausea, or blurred vision. In both conditions, there is a potential risk associated with the 
loss of confidentiality of study data.
PA participants have a greater risk of violation of confidentiality and/or privacy in the 
study, as they will be participating in a facility-based group exercise program. Study 
participants will be encouraged to socialize with one another to promote group cohesion,
and complete confidentiality cannot be guaranteed as this space will be utilized by other
Durham VAMC patients. Additionally, exercise logs with participant names and exercise 
prescriptions will be available to patients during their exercise time. Access to these 
cards will be limited to study participants; however, it is possible that these may be 
visible to others using the exercise space as participants move from station to station. 
Importantly, no PHI or other Pll, other than participant name, will be included on these 
documents.
Regular moderate-intensity exercise should enhance rather than jeopardize health 
status, and potential serious adverse events (SAE) for participants in this project are 
not expected. Regardless, we will minimize potential risk by careful screening of 
potential participants. Serious adverse events will be promptly reported to the VA IRB 
as required. All project staff will complete educational units required by the Durham 
VAMC Human Subjects Committee.
Participants may benefit from this study by improving their health through 
increased physical activity participation.
DATA SAFETY AND MONITORING
The individuals responsible for data safety and monitoring will be the Pl, the Research 
Coordinator, and the study Co-Investigators (Drs. Morey, Beckham, and Bosworth). 
Further data safety and monitoring will be provided by the Pl. There will be several 
ongoing mechanisms for monitoring and reporting of adverse events:
1)
ongoing participant contact via study personnel; 2) study telephone number 
provided to participants to report concerns related to study participation; and 3) 
weekly meetings between the Pl and study personnel.
The Pl will meet at least weekly with study personnel to discuss participants' reactions to
the intervention, proper delivery of the intervention, and any adverse events or 
unanticipated problems. Monthly meetings between the investigators and the Research 
Coordinator will allow for ongoing progress reports, including the number of participants 
currently involved in the study groups, attrition rates, and scheduled data collection 
from participants, as well as notification and review of any adverse events (AE). Safety 
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
12

monitoring for AEs will be conducted in real time by the Pl and/or Research Coordinator. 
The following information about adverse events will be collected: 1) the onset and 
resolution of the AE, 2) an assessment of the severity or intensity (use existing grading 
scales whenever possible), 3) an assessment of the relationship of the event to the 
study (definitely, probably, possibly or not related), 4) organ system involved, and 5) 
action taken (e.g., none, referral to physician, start or increase concomitant medication).
The Pl will determine the severity of the event, will assign attribution to the event, and 
will monitor the event until its resolution. Any adverse events will be reported to the IRB 
in accordance with the local Human Research Protection Program's Standards of 
Practice.
DATA MANAGEMENT AND SECURITY
Several types of data will be collected over the course of the study. As described under 
the Request for Waiver or Alteration of Informed Consent and HIPAA Authorization for 
Research, PHI to be collected during recruitment activities includes name, age, medical 
history, address, telephone number, and social security number. Other data to be 
collected over the course of the study (as described in the HIPAA authorization) include 
name; address; phone number; social security number; dates of study visits; and 
account numbers (for Veterans who have bank accounts, payment will be issued via 
direct deposit, which requires a Vendorizing Coversheet that asks for account information
and VA Form 10-7078 to be obtained). Additionally, a unique study ID will be assigned to 
each participant. Sources of health information include medical history and physical 
exam information, progress notes in CPRS, laboratory test results, survey responses, 
alcohol and/or drug use information, and mental health notes. This information will be 
used for research purposes only.
DATA ANALYSES
AIM 1-Feasibility: This AIM revolves around testing the feasibility, fidelity and 
acceptability of the proposed exercise intervention. We will track number of patients 
contacted, screened, eligible, and enrolled to determine acceptability rates. Reasons 
for refusal will be tracked. Once enrolled, we will monitor the fidelity of the intervention
by measuring adherence to the intervention arm.
Feasibility proportions for screening and recruitment will be calculated at the end of the 
intervention using the following:
1. Source of patients screened for potential enrollment will be determined by 
calculating the number of patients enrolled from the Contact Database and 
Durham VAMC clinics.
2. Proportion of patients recruited will be calculated as the number of patients 
deemed potentially eligible and contacted for enrollment divided by the total 
number of patients enrolled.
Fidelity proportions will be calculated for adherence and retention at the end of the 
intervention using the following:
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
13

1. Proportion adherent to in-class attendance will be computed as the number of
sessions attended divided by the number of possible sessions among all 
randomized subjects.
2. Proportion retention will be computed by dividing the number of retained 
subjects at the end of the intervention by the total number randomized into the 
study.
We will calculate these rates of retention and adherence and their respective 
confidence intervals overall and by group. While non-powerful, we will assess if these 
rates differ by chi-square test of proportion and Poisson regression respectively. In a 
series of sensitivity tests, we will assess if adherence overall was impacted by 
demographic or symptomatic variables (such as obesity, severity of pain or PTSD 
symptoms).
AIM 2-Efficacy: This study is a randomized two-arm pilot study with replicate measures 
at two time points: baseline and 12 weeks. Analysis will be based on intention to treat 
principles; the overall intervention effect will be measured for the entire sample 
assuming participants have followed their randomized assignment. The main conclusions
drawn from this trial will be based on the pre-specified hypotheses outlined below and 
will be tested with two-sided p-values at the standard 0.05 level. Statistical analyses will 
be performed using SAS (Version 9: SAS Institute Cary NC) and SPSS.
Following the Good Clinical Practice Guidelines22 for the analysis of a clinical trial, we will 
employ mixed models,23 analyze under an Intent to Treat (ITI) criteria, and control for 
baseline (leaving 2 post-randomization measures per outcome) and assess the impact of
Time, Treatment Group and the interaction of these variables on the outcomes. Relative 
to the usual repeated measures designs, mixed models have several advantages: (1) 
missing values present no particular difficulties in estimation and the estimates are 
unbiased as long as the set of variables leading to MAR are estimated, (2) the usual 
assumption of conditional independence (compound symmetry) used in standard 
repeated measures need not be made, and (3) the actual times of measurement need 
not be equivalent across subjects. Controlling for the individual baseline values for the 
particular outcomes, the trajectories over time and differences in those trajectories will 
be assessed. Following the statistical principles section from the International 
Conference on Harmonization,24 we will select covariates (e.g., age, race, number of 
comorbidities) for the primary models a priori, but we also will conduct auxiliary 
sensitivity analyses that evaluate whether potential group imbalances bias the 
treatment effect estimate. These analyses will be performed using conventional testing 
for confounding.25
As defined, the overall test of the intervention effect will be the joint effect of group 
and group*time on 2 df ((31 and (32) assessing an overall effect of group, and if this 
group effect is constant over time. If significant, follow-up tests will assess where group
differences lie. In particular, we note that if the time by group interaction is rejected, 
we will test if the groups differ at the end of 12 weeks (a test of effect at the 
completion of the intervention). Lf time and funds permit, we may also test if the 
groups differ several weeks post-intervention (a test of the durability of the effect).
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
14

We note that we have listed numerous measures to be analyzed as outcomes but have 
listed only 3 outcomes as primary (physical activity, aerobic endurance, PTSD 
symptoms). We will not adjust for Type-I error rate for these primary outcomes. Rather, 
in any resulting publications, readers will be informed of the multiple testing issues and 
the exploratory nature of the investigations.
Compliance. It will be of particular interest to assess the mediation impact of level of 
compliance during the intervention (days of exercise) on the estimated effects, to derive 
a 'perprotocol' effect estimate.22' 24 Compliance and level of exercise will be included in 
the models to assess the sustainability of the intervention and to develop a measure of 
dose-response for the intervention. However, these analyses will need to be carefully 
controlled, since 'compliance' is not randomized and may be confounded by other 
factors such as PTSD symptom severity and functional status. If fully controlled models 
demonstrate a compliance effect, such evidence will provide support to the notion that 
the intervention is the agent affecting physical activity behavior and cardiovascular 
improvements.
Mobile Device Use Telephone Survey. Univariate statistics and frequencies (% of 
respondents) will be used to assess and summarize responses to the 8-item telephone 
survey about mobile device use.  
Post-Program Evaluation Interviews. We plan to use directed content 
analysis/applied thematic analysis, organizing the data in response to the questions 
contained in the interviews. Transcripts will be examined for common and emergent 
themes as well as a priori themes. Open coding will be used to identify manifest and 
latent content, followed by axial coding to identify patterns between code categories. Dr.
Hall and the Qualitative Research Analyst will develop a codebook of definitions and 
exemplars, which will be presented to the team for feedback. We will also employ theme 
matrix techniques to facilitate data analysis and presentation. Initial matrices will be 
developed and further refined. Quotes will be separately aggregated and displayed in 
matrices with columns identifying critical dimensions of the quotes. NVivo 11 qualitative 
software will be used to assist with qualitative data analysis. At least a subset of 
interviews will be coded by both Dr. Hall and the QRA to determine and facilitate inter-
coder agreement. First cycle coding approaches to be utilized include elemental (i.e., 
descriptive, in vivo, and process coding) and affective (i.e., emotion, values, evaluation 
coding) methods. Both inductive and deductive codes will be created. Second cycle 
coding processes will involve analytic memos about the data and reconfiguration of the 
first cycle codes. Pattern coding will allow us to group the summaries into a smaller 
number of themes, categories, and/or constructs.
Missing Data and Attrition Rates. Because the main predictors of interest, 
treatment group and demographics, are collected at baseline, we do not anticipate 
much missing data. We do, however, anticipate missing values in the longitudinal 
outcomes owing to dropout or an inability to reach the patient by phone. Missing data 
problems are ubiquitous in aging research. Participants are, in general, compliant to 
protocols, but drop out due to a variety of reasons, primarily due to health events, 
which render them unable to complete protocols.
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
15

Based on our previous studies of physical activity and older adults, we project an 
attrition rate of 20%. We will use several strategies proven to enhance retention in our 
past projects. First, the intervention strategy itself is designed to improve compliance 
and retention. The primary theoretical basis of this intervention relies heavily on Social 
Cognitive Theory (SCT}, 26 in which behavior influences, and is influenced by, within 
person factors and factors in the social and physical environments. The primary 
intervention strategy is designed to enhance self-efficacy, an important predictor of 
physical activity in older adults.27•28 Elements of SCT integrated into this intervention 
include modeling, self-monitoring, goal setting, reinforcement, and cognitive reframing. 
Second, our study staff will strive to establish positive relationships with participants 
(e.g., in scheduling, testing, telephone reinforcement, and exercise instruction 
interactions}. Third, we will provide incentives for all study assessments. Participants 
will receive $50 for baseline, $75 for Week 12 assessments, $50 for Week 24 
assessments (Usual Care wait-list control only}, and $25 for 1 Year assessments 
(completely mail-based}. Total participant payment is thus $150/$200 if all visits and 
follow-ups are completed. Finally, our weekly contact provides a means for quickly 
identifying non-adherent participants and "recovering" lost participants early.
REFERENCES
1.
Boscarino JA. A prospective study of PTSD and early-age heart disease mortality 
among Vietnam veterans: implications for surveillance and prevention. 
Psychosomatic Medicine. 2008;70(6):668-676.
2.
Buckley TC, Mozley SL, Bedard MA, Dewulf AC, Greif J. Preventive health behaviors, 
health-risk behaviors, physical morbidity, and health-related role functioning 
impairment in veterans with post-traumatic stress disorder. Military Medicine. 
2004;169(7):536-540.
3.
Dedert EA, Calhoun PS, Watkins LL, Sherwood A, Beckham JC. Posttraumatic stress 
disorder, cardiovascular, and metabolic disease: a review of the evidence. Annals 
of Behavioral Medicine. 2010;39(1):61-78.
4.
Hall KS, Beckham JC, Bosworth HB, Sloane R, Pieper CF, Morey MC. PTSD is 
negatively associated with physical performance and physical function in older 
overweight military veterans. Journal of Rehabilitation Research and 
Development.2014; 51(2):285-96..
5.
The Management of Post-Traumatic Stress Working Group. VA/DoD Clinical Practice 
Guideline for Management of Post-traumatic Stress. In: Department of Veterans 
Affairs DoD, ed. Vol 2.0: Washington, D.C.; 2010.
6.
Chwastiak LA, Rosenheck RA, Kazis LE. Association of psychiatric illness and 
obesity, physical inactivity, and smoking among a national sample of veterans. 
Psychosomatics. May-Jun 2011;52(3):230-236.
7.
Manger TA, Motta RW. The impact of an exercise program on posttraumatic stress 
disorder, anxiety, and depression. International journal of emergency mental 
health. Winter 2005;7(1):49-57.
8.
McAuley E, Jerome GJ, Marquez DX, Elavsky S, Blissmer B. Exercise self-efficacy in 
older adults: social, affective, and behavioral influences. Annals of behavioral 
medicine : a publication of the Society of Behavioral Medicine. Winter 
2003;25(1):1-7.
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
16

9.
Mori DL, Sogg S, Guarino P, et al. Predictors of exercise compliance in individuals 
with Gulf War veterans illnesses: Department of Veterans Affairs Cooperative Study
470. Mil Med. Sep 2006;171(9):917-923.
10.
Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the 
Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on 
Early Detection of Persons with Harmful Alcohol Consumption--II. Addiction. Jun 
1993;88(6):791-804.
11.
Bohn MJ, Babor TF, Kranzler HR. Validity of the druge abuse screening test (DAST-
10) in inpatient susbtance abusers: Problems of drug dependence. Addiction. 
1991;88(6):791-804.
12.
Weathers FW, Blake DD, Schnurr, PP, Kaloupek, DG, et al. The Clinician-
Administered PTSD Scale for DSM-V. www.ptsd.va.gov.
13.
Weathers FW, Litz BT, Keane TM, Palmieri PA, Marx BP, Schnurr PP. The PTSD 
Checklist for DSM-5 (PCL-5). 2013:Scale available from the National Center for 
PTSD at www.ptsd.va.gov.
14.
Sundman MH, Hall EE, Chen N. Examining the relationship between head trauma 
and neurodegenerative disease: a review of epidemiology, pathology and 
neuroimaging techniques. Journal of Alzheimers Disease and Parkinsonism 4: 137.
15.
Ware JE, Jr. SF-36 health survey update. Spine. Dec 15 2000;25(24):3130-3139.
16.
Germain A, Hall M, Krakow B, Katherine Shear M, Buysse DJ. A brief sleep scale for 
Posttraumatic Stress Disorder: Pittsburgh Sleep Quality Index Addendum for PTSD. 
Journal of anxiety disorders. 2005;19(2):233-244.
17.
Kohl HW, Blair SN, Paffenbarger RS, Jr., Macera CA, Kronenfeld JJ. A mail survey of 
physical activity habits as related to measured physical fitness. Am J Epidemiol. Jun
1988;127(6):1228-1239.
18.
Cutrona CE, Russell DW. The provisions of social relationships and adaptation to 
stress. In: W.H. Jones & D. Perlman, eds. Advances in personal relationships. 
Greewich, CT: JAI Press; 1987:37-67.
19.
Pfeiffer E. A short portable mental status questionnaire for the assessment of 
organic brain deficit in elderly patients. J Am Geriatr Soc. 1975;23(10):433-441.
20.
Podsiadlo D, Richardson S. The timed up & go: a test of basic functional mobility for
frail elderly persons. Journal of the American Geriatrics Society. 1991;39:142-148.
21.
Balke B. A simple field test for the assessment of physical fitness. CARI Report. 
1963;63:18.
22.
Committee for Proprietary Medicinal Products (CPMP): points to consider on 
adjustment for baseline covariates. Statistics in Medicine. 2004;23(5):701-709.
23.
Laird N, Ware, JH,. Random-effects models for longitudinal data. Biometrics. 1982; 
38:963-974.
24.
International Conference on Harmonisation: Statistical Principles in Clinical Trials 
(E9)1997.
25.
Berger V. Selection bias and covariate imbalances in randomized clinical trials. 
Hoboken, NJ: Wiley; 2005.
26.
Bandura A. Self-Efficacy: The Exercise of Control. New York: W.H. Freeman; 1997.
27.
McAuley E, Blissmer B. Self-efficacy determinants and consequences of physical 
activity. Exercise and sport sciences reviews. Apr 2000;28(2):85-88.
28.
McAuley E, Jerome GJ, Elavsky S, Marquez DX, Ramsey SN. Predicting long-term 
maintenance of physical activity in older adults. Preventive medicine. Aug 
2003;37(2):110-118.
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
17

29.
Kohl HW, Blair SN, Paffenbarger RS, Jr., Macera CA, Kronenfeld JJ. A mail survey of 
physical activity habits as related to measured physical fitness. Am J Epi. 
1988;127(6):1228-1239.
30.
McAuley, E. (1992). The role of efficacy cognitions in the prediction of exercise 
behavior in middle-aged adults. Journal of Behavioral Medicine, 15(1), 65-88.
31.
Kozma, A., & Stones, M. J. (1980).  The measurement of happiness: Development of
the Memorial University of Newfoundland Scale of Happiness (MUNSH).  Journal of 
Gerontology, 35, 906-912
32.
Cohen, S., Kamarck, T., and Mermelstein, R. (1983). A global measure of perceived 
stress. Journal of Health and Social Behavior, 24, 386-396.
33.
Zelinski M, Gilewski MJ. A 10-item rasch model memory self-efficacy scale. Aging 
Ment Health. 2004;8(4):293–306.
34.
Spielberger, C. D., Gorsuch, R. L., Lushene, R., Vagg, P. R., & Jacobs, G. A. (1983). 
Manual for the State-Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists
Press.
35.
Spielberger, C. D., Gorsuch, R. L., Lushene, R., Vagg, P. R., & Jacobs, G. A. (1983). 
Manual for the State-Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists
Press
Physical Activity and PTSD, Hall, version 10 dated 8.6.19
18