Feasibility and Acceptability of an Integrative Therapy for Symptom Management in Persons With Pulmonary Hypertension
Phase: NA
Conditions: Pulmonary Hypertension, Chronic Disease
Sponsor: Ohio State University

 IRB Protocol Number: 
2017H0022 
 Version Date 
01/17/2019 
IRB Approval date:  
Clean 
 
 
 
 
Official Title: Urban Zen Integrative Therapy for Person 
with Pulmonary Hypertension 
NCT Number: NCT03194438 
Document Name: Study Protocol and Statistical Analysis Plan 
Document Date: January 17, 2019 
 
 
 
 
 
 

 IRB Protocol Number: 
2017H0022 
 Version Date 
01/17/2019 
IRB Approval date:  
Clean 
 
 
THE OHIO STATE UNIVERSITY  
Institutional Review Board  
  
 
Feasibility and Acceptability of Integrative Therapy in Symptom Management for 
Persons with Pulmonary Hypertension 
 
Tania T. Von Visger, APRN, Ph.D. (c), CNS, CCNS, PCCN 
Ph.D. candidate 
The Ohio State University College of Nursing 
 
Mary Elizabeth Happ, Ph.D., RN, FGSA, FAAN 
Associate Dean for Research and Innovation, The Ohio State University College of Nursing 
 
Linda L. Chlan, Ph.D., RN, FAAN 
Associate Dean for Nursing Research, Mayo Clinic 
 
Susan E Thrane, Ph.D., RN  
Assistant Professor, The Ohio State University College of Nursing 
 
Maryanna D. Klatt, Ph.D.  
Associate Professor, Ohio State University College of Medicine 
 
Annette DeVito Dabbs, Ph.D., RN 
Professor of Nursing - The U. of Pittsburgh School of Nursing 
 
Research Members: 
 
Lori Bowers, UZIT Therapist 
 

 IRB Protocol Number: 
2017H0022 
 Version Date 
01/17/2019 
IRB Approval date:  
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Research Protocol  
  
 
I. 
Introduction 
 
 
Patients with severe, life-limiting cardiopulmonary (CP) conditions face particularly 
difficult symptom management challenges and poor health-related quality of life (HRQoL) 
(Ståhl et al., 2005; Taichman et al., 2005).  Interventions are desperately needed to ameliorate 
symptom burden and promote quality of life in persons with severe and debilitating chronic CP 
conditions.  Fifteen million Americans reported that they have been told by their healthcare 
providers that they have Chronic Obstructive Pulmonary Disease (COPD) and among these, 
64.2% reported that shortness of breath interferes with their quality of life (Kosacz et al., 2012). 
Patients with heart failure experience high symptom prevalence (shortness of breath, lack of 
energy, and insomnia) and high symptom burden (difficulty sleeping) (Zambroski, Moser, Bhat, 
& Ziegler, 2005). Patients with pulmonary hypertension (PH) reported at least 17 bothersome 
symptoms with shortness of breath and fatigue to be the most prevalent with high intensity 
score (Matura, McDonough, & Carroll, 2014).There is a gap in scientific knowledge about the 
therapeutic effectiveness of non-pharmacologic, integrative approaches to symptom 
management in adults with chronic cardiopulmonary disease. Urban Zen Integrative Therapy 
(UZIT) is a tailored, multicomponent therapy featuring a combination of integrative modalities 
including 1) essential oils, 2) gentle movement/restorative poses, 3) body-awareness 
meditation, and 4) Reiki. UZIT is designed to target symptoms associated with complex 
chronic illness. The UZIT program is currently being implemented in a variety of health care 
settings (i.e., intensive care, inpatient, hospice and palliative care). However, feasibility and 
acceptability have not been evaluated in community-dwelling persons with chronic, life-limiting 
cardiopulmonary disease as an integrative approach to reducing symptom presence and 
severity.  
 
II. 
Objectives   
 
The primary goal of this study is to determine the feasibility and acceptability of a 6-
week (Freedenberg, Thomas, & Friedmann, 2015) multi-component integrative therapy 
program, UZIT, for adults with chronic, life-limiting cardiopulmonary disease. The secondary 
goal is to explore the preliminary efficacy of UZIT in symptom management. Pulmonary 
hypertension (PH) presents an excellent model of a severe, life-limiting cardiopulmonary 
condition with high symptom burden and poor outcomes suitable for this scientific inquiry. 
  
This study will use a single group repeated-measures design to address the following 
Specific Aims:  
Aim #1:  To determine the feasibility of a 6-week UZIT intervention in community-
dwelling adults with PH.  Feasibility will be determined by 1) recruitment rate (>40% recruited 
from those approached), 2) enrollment (>two participants /month) (Carter et al., 2013; 
Uebelacker et al., 2010), 3) home practice (> 1/week), and 4) retention rate (>70% of 
participants remaining at study completion). We will also explore UZIT interventionists’ 
perception about study feasibility. 
Hypothesis 1: UZIT will meet feasibility targets for community-dwelling adults with PH. 

 IRB Protocol Number: 
2017H0022 
 Version Date 
01/17/2019 
IRB Approval date:  
Clean 
 
 
 
Aim #2:  To determine the acceptability of UZIT among community-dwelling adults with 
PH for symptom management. Acceptability will be determined by participants’ evaluation of 
the UZIT program (composite mean System Usability Scale score > 5, scale 1-7),(Brooke, 
1986) and session completion rate (at least 5 of 6 sessions [83% attendance] (Campo et al., 
2013; Cohen et al., 2007; Lee et al., 2010; Lengacher et al., 2011; Palumbo, Wu, Shaner-
McRae, Rambur, & McIntosh, 2012) by the participants retained at the study end. An 
exploratory sub-aim (Aim 2-A) is to determine what components of the UZIT program are 
preferred by adults with PH. We will also explore UZIT interventionists’ perception about 
participants’ acceptability of the UZIT intervention. 
Hypothesis 2: UZIT will meet acceptability standards among community-dwelling 
adults with PH.  
 
Aim #3: To explore the preliminary efficacy of UZIT intervention. 
Aim #3a: To explore the preliminary efficacy of weekly UZIT sessions on 
dyspnea, pain, fatigue and anxiety.  
Aim #3b: To explore the preliminary efficacy of a 6-week UZIT program on PH-related 
symptoms and HrQoL.  
Hypothesis 3a: Patients will report reduced presence and intensity of dyspnea, pain, 
fatigue and anxiety after each UZIT session.  
Hypothesis 3b: Patients will report a decrease in the presence, severity, and activity 
interference for PH-related symptoms and improvement in HrQoL after UZIT program 
compared to baseline.  
 
III. Background and Rationale  
 
Despite medical and pharmacological advances in treatment, 50-55% of persons with 
PH will die within three years after diagnosis (Benza et al., 2010). Medical management often 
involves life-long complex pharmacological treatment requiring high levels of skill, knowledge, 
and social support. Clusters of bothersome symptoms such as chest pain, anxiety, insomnia, 
dyspnea, and fatigue can overwhelm patients’ ability to manage daily activities and medication 
treatment regimens. Side effects of treatment induce additional noxious symptoms (Mathier, 
McDevitt, & Saggar, 2010). The high prevalence of physical symptoms, depression, and 
anxiety among adults with PH (McCollister et al., 2010) was confirmed in my prior work. There 
is also a positive correlation between reported symptoms and reduction in health-related 
quality of life (HRQoL) (Von Visger, T., Kuntz, K., Phillips, G., Happ, MB., Sood, N, 2014). A 
literature review of PubMed and CINAHL databases using the terms “integrative therapy”, 
“complementary therapy” AND “pulmonary hypertension” found no published report of 
complementary, integrative therapy interventions to alleviate symptoms in adults with PH.  
 
This study will fill a gap in symptom science by exploring an integrative therapy 
approach to treating significant and burdensome disease-related and medication-related 
symptoms commonly experienced by persons with chronic, life-limiting CP disease. The 
individual therapies within the UZIT program are supported by a body of evidence 
documenting efficacy in reducing symptoms of stress, anxiety, depression, insomnia, pain, 
fatigue in persons with cancer, diabetes, cardiac, renal, inflammatory, neurological, and 
pulmonary chronic conditions (Ayan et al., 2013; Bagheri-Nesami, Espahbodi, Nikkhah, 

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Shorofi, & Charati, 2014; Baldwin, Fullmer, & Schwartz, 2013; Bernardi, Amorim, Zandonade, 
Santaella, & Barbosa Jde, 2013; Boehm, Bussing, & Ostermann, 2012; Hofmann, Sawyer, 
Witt, & Oh, 2010; Lavretsky et al., 2013; Lytle, Mwatha, & Davis, 2014; Newham, Wittkowski, 
Hurley, Aplin, & Westwood, 2014; S. E. Thrane, Maurer, Ren, Danford, & Cohen, 2016; 
Wurtzen et al., 2013). There is currently an absence of evidence investigating these integrative 
therapies in persons with CP conditions or studies that investigate combination therapies, such 
as the UZIT program, in an outpatient setting. This study is designed to address this gap by 
measuring immediate change in symptoms after each UZIT session as well as a change over 
time in symptoms and HrQoL. Pulmonary hypertension (PH) is the chronic condition selected 
for UZIT testing because it represents the most rapidly progressive CP disease with many 
severe symptoms and high mortality.  
 
Patients with chronic, life-limiting cardiopulmonary (CP) conditions face difficult symptom 
management challenges. Pulmonary hypertension (PH), a CP condition with high symptom 
burden, serves as an excellent model for symptom management intervention development and 
testing. Characterized by high mean pulmonary arterial pressures, PH affects an estimated 
15,000 Americans and shares symptom characteristics common to several life-limiting chronic 
conditions (McLaughlin et al., 2009). Despite medical advancements, the average 3-year 
mortality rate for pulmonary arterial hypertension (an important PH subtype) continues to be 
high, above 50% (Badagliacca et al., 2012; Benza et al., 2010). Patients with PH require 
complex management (Hoeper et al., 2013; Keogh et al., 2011; Krasuski et al., 2011) and 
experience frequent hospitalizations, overwhelmed by a cluster of symptoms such as, pain, 
anxiety, insomnia, dyspnea, dizziness, and fatigue (Matura et al., 2012). Moreover, 
bothersome medication-related side effects include nausea, cough, dry mouth, and jaw pain, 
adding to the disease-related symptoms (Mathier, McDevitt, & Saggar, 2010). The combination 
of these symptoms makes effective self-management of PH extremely challenging for patients 
and caregivers. High PH-related symptom burden is correlated with worse health-related 
quality of life (HRQoL) (Matura et al., 2014). Evidence-based non-pharmacological symptom 
treatments are desperately needed to improve HRQoL for these patients. 
 
Approximately 36% of adults in the United States use integrative therapies for symptom 
management (Clarke, Black, Stussman, Barnes, & Nahin, 2015), and some approaches have 
shown benefit in the reduction of symptom intensity in other disease populations (Asmaee 
Majid, Seghatoleslam, Homan, Akhvast, & Habil, 2012; Birocco et al., 2012; Conrad & Adams, 
2012; Hoffman, 2012; Igarashi, 2013; Klainin-Yobas, Cho, & Creedy, 2012; Newham et al., 
2014; S. Thrane, 2013; S. Thrane & Cohen, 2014). In a systematic review of 25 randomized 
controlled trials published in peer-reviewed journals, integrative therapy demonstrated a 
dramatic reduction (moderate to large effect sizes) in pain and anxiety in children and 
adolescents with cancer (S. Thrane, 2013). Although integrative therapy use is common 
worldwide, Thrane’s analysis was limited by the small number of studies that met the inclusion 
criteria. Individual integrative therapy modalities have been studied for therapeutic response 
(Andersen et al., 2013; Baldwin et al., 2013; Fung, Tsang, & Chung, 2012; Gross et al., 2009; 
Lytle et al., 2014; Nyklicek, Dijksman, Lenders, Fonteijn, & Koolen, 2014; Sharma, Robbins, 
Wagner, & Colgrove, 2015; Yadav, Magan, Mehta, Sharma, & Mahapatra, 2012a), however, 
combination therapy may provide benefits superior to a single approach. In a retrospective 
chart review of 6,587 hospitalized cardiovascular patients who received integrative therapy, 
the application of two or more integrative therapies was associated with significant reductions 
in anxiety compared to one treatment (Johnson et al., 2014). Two combination approaches of 

 IRB Protocol Number: 
2017H0022 
 Version Date 
01/17/2019 
IRB Approval date:  
Clean 
 
 
1) mind-body therapy with energy therapy and 2) Traditional Chinese medicine reduced 
patients’ anxiety scores significantly when compared to a single therapy (massage) (Johnson 
et al., 2014). While this study included a large sample size, it did not take into account the 
pharmacological effects on pain and anxiety nor evaluate/ monitor intervention fidelity. There is 
relatively little research testing combination therapy on symptom outcomes. However, 
combination integrative therapies such as Traditional Chinese Medicine and Ayurvedic 
Medicine have been used for centuries (A. Burke, Kaptchuk, Lao, Weber, & Killen, 2016; 
Weber & Killen, 2015), and combination approaches are currently gaining popularity in 
community and in-patient settings. Co-application of 4 integrative therapies, as in Urban Zen 
Integrative Therapy (UZIT), may have synergistic effects on symptom management and 
warrants examination. 
 
To obtain additional information pertaining to the study aims of UZIT feasibility and 
acceptability, we plan to conduct a focus interview with UZIT interventionists after all UZIT 
sessions are delivered to study participants. Exploring interventionists’ overall impressions 
about the study conduct using complex intervention such as UZIT is important in future 
refinement of the intervention in a larger scale research. Because UZIT is a multi-component 
complementary health intervention, intervention fidelity assurance is critical to the internal 
validity. Prior research demonstrated the importance of obtaining interventionists’ perception in 
a complex intervention such as Motivational Interviewing research (Kimber et al, 2017), and 
behavioral health research (Wyatt, 2010 & Carpenter et al, 2013). The questionnaire will also 
solicit interventionists’ perception about patients’ acceptability of UZIT intervention. Because 
interventionists had close therapeutic relationship with study participants throughout the 
course of study period, their perception is invaluable to the overall determination of UZIT 
acceptability. Interventionists’ audio recorded comments will be transcribed verbatim, coded 
and categorized for common themes using NViVo qualitative data analysis program. 
 
   
Urban Zen Integrative Therapy (UZIT)  
 
UZIT is a multi-modal integrative therapy that includes: 1) essential oils, 2) gentle 
movement/ restorative poses, 3) body-awareness meditation, and 4) Reiki therapy tailored to 
individual patients’ symptoms (Kligler et al., 2011). The basis from which these therapies are 
applied stems from mindfulness training and yoga practices. UZIT is designed to address the 
classic symptoms associated with chronic illness: exhaustion, pain, anxiety, nausea, insomnia, 
and constipation. Through the targeted application of a chosen essential oil, patients practice 
awareness in recognizing body sensations through relaxation and calmness. Restorative yoga 
poses (such as side-lying child’s pose and supported relaxation pose) are used to enhance 
relaxation and release tension. Each session is provided by the UZIT therapist in a synergistic 
and collaborative approach with strong emphasis on patients’ input about bothersome 
symptoms. At present, more than 900 UZIT sessions are already documented at OSUWMC.  
 
A quasi-experimental study comparing two independent patient groups before (n = 89) 
and after (n= 74) UZIT implementation in an oncology unit showed improvements in patient 
mood and health state (Kligler et al., 2011). Patients who received UZIT reported significantly 
less tension, depression, fatigue, increased mobility, and less overall mood disturbance 
(Kligler et al., 2011). Although there were no between-group differences in pain, a statistically 

 IRB Protocol Number: 
2017H0022 
 Version Date 
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IRB Approval date:  
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significant decrease in pain was observed in the UZIT group after vs. before therapy. While 
UZIT is available in some inpatient and hospice settings, application of this therapy among 
community-dwelling adults with chronic conditions is lacking. Formal scientific evaluation of 
this integrative approach for symptom self-management in patients with chronic life-
limiting cardiopulmonary conditions, such as PH, is urgently needed.  Evidence for each 
component of UZIT is reviewed below. 
 
Essential Oil.  
  
Application of lavender, citrus, and peppermint essential oils demonstrated therapeutic 
benefits of symptom alleviation for insomnia, pain, stress, anxiety, and nausea respectively in 
a variety of adult populations (Ayan et al., 2013; Bagheri-Nesami et al., 2014; Hirokawa, 
Nishimoto, & Taniguchi, 2012; Igarashi, 2013; Lytle et al., 2014; Matsumoto, Asakura, & 
Hayashi, 2014). Across most studies, 5-10 minutes inhalation of essential oil was adequate to 
achieve immediate symptom improvement. In a study of patients undergoing routine 
hemodialysis needle insertion, procedural pain severity was significantly improved at the end 
of three treatments among those who received 5-minutes inhalation of lavender oil before the 
procedure as compared to a non-treatment control group (Bagheri-Nesami et al., 2014). In 
another study, pregnant women assigned to receive 5-minute inhalation of lavender or citrus 
essential oils showed a similar statistically significant reduction in tension and anxiety 
compared to before treatment (Igarashi, 2013). A reduction in acute stress biomarker (salivary 
chromogranin) and improved mood states were observed among healthy college students 
after 10-minute inhalation of Japanese Citrus Yuzu essential oil (Matsumoto et al., 2014). 
Improved sleep quality was reported by college student volunteers exposed to lavender oil 
throughout the night during sleep for five consecutive nights (Hirokawa et al., 2012). A 
systematic review demonstrated a reduction in anxiety, depression, and improved sleep in 
cancer patients (Boehm et al., 2012). Taken together, reduction in pain, tension, and anxiety 
and improved sleep quality were reported with lavender oil (Bagheri-Nesami et al., 2014); 
reductions in stress and anxiety were observed with citrus essential oil (Goes, Antunes, Alves, 
& Teixeira-Silva, 2012; Matsumoto et al., 2014); reduction in nausea was shown with 
peppermint oil (Ferruggiari, Ragione, Rich, & Lock, 2012). Evidence from these studies, 
however, is limited due to the lack of randomized controlled trial (RCT) study design, small 
sample sizes, and varied dose delivery. Demonstrated benefits in symptom reduction justify 
more rigorous testing of essential oils to address similar symptoms in adults with PH. 
 
 
   Gentle movement/Restorative Poses.  
Derived from yoga practice, gentle movement/restorative poses included supported 
recumbent positions meant to induce deep relaxation. There is limited evidence available 
specifically regarding gentle movement/restorative poses. However, evidence for the 
therapeutic benefits of yoga practice is substantive. Yoga practice (60-minutes, once a week 
for 6-12 weeks) among persons with chronic illnesses demonstrated improvement in anxiety, 
depression, and quality of life (Bernardi et al., 2013; Lavretsky et al., 2013; Newham et al., 
2014; Siddarth, Siddarth, & Lavretsky, 2014; Vadiraja et al., 2009; Yadav, Magan, Mehta, 
Sharma, & Mahapatra, 2012b). Reduction in disease-specific symptoms and serum cortisol 
were observed among patients with chronic illnesses (diabetes, hypertension, mental stress, 
and musculoskeletal pain) (Yadav et al., 2012b). Reductions in fatigue and insomnia were 

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demonstrated among community-dwelling patients with stage III and IV breast cancer 
(Vadiraja et al., 2009). While these studies reported the therapeutic benefit of yoga, their 
results are limited by small sample size, lack of randomization, and inconsistent intervention 
dose. Reported improvements in stress, anxiety, depression, mood, insomnia, and fatigue as a 
result of yoga practice among chronically ill adults (Sharma et al., 2015; Yeung et al., 2014) 
support testing gentle movement/restorative poses in controlled trials of symptom 
management and quality of life improvement.  
 
Body-awareness meditation.  
 
Body-awareness meditation is a type of mindfulness practice that focuses on one’s 
awareness of the present bodily state. From the perspective of psychological well-being, 
mindfulness is a state of present-centered, attention-awareness, and open receptivity to the 
present (Brown & Ryan, 2003). Mindfulness is a process of bringing a certain quality of 
attention to moment-by-moment experience (Kabat-Zinn, 2005), and is defined as “a process 
that leads to a mental state characterized by nonjudgmental awareness of the present 
experience, including one’s sensations, thoughts, bodily states, consciousness, and the 
environment, while encouraging openness, curiosity, and acceptance”(p. 169) (Hofmann et al., 
2010). Recent meta-analyses using this definition of mindfulness indicate that mindfulness-
based therapy (MBT) is effective in treating depression and anxiety among patients with 
chronic conditions (Azulay, Smart, Mott, & Cicerone, 2013; Hofmann et al., 2010; S. Jain et al., 
2012) and those with psychiatric illness.(Klainin-Yobas et al., 2012). Reduction in anxiety and 
depression among patients with cancer were observed using MBT (Hofmann et al., 2010; 
Wurtzen et al., 2013). MBT showed reduction in anxiety, depression, and suicidal ideation 
among veterans (Serpa, Taylor, & Tillisch, 2014), reduction in stress, insomnia and fatigue 
among patients with fibromyalgia (Cash et al., 2014), reduction in stress among caregivers 
(Hou et al., 2014; F. A. Jain, Nazarian, & Lavretsky, 2014; Whitebird et al., 2013), and 
reduction in anxiety and depression among solid organ transplant recipients (Gross et al., 
2010). MBT intervention among patients with generalized anxiety disorder showed statistically 
significant reductions in anxiety, depression, and worry (Asmaee Majid et al., 2012). Anxiety, 
depression, and stress improved in cardiac patients undergoing percutaneous intervention 
who received MBT compared to a control group (Nyklicek et al., 2014). MBT is acceptable and 
feasible to patients with diabetes (van Son et al., 2013) and coronary heart disease for 
improved sleep, increased relaxation, and acceptance of illness (Keyworth et al., 2014). 
Evidence supporting the use of MBT is substantive with several RCTs using large sample 
sizes across multiple populations. In this proposed study, mindfulness is defined as present-
centered, attention-awareness (Brown & Ryan, 2003) of symptoms using body-awareness 
meditation technique.  
 
 
 
Reiki.  
 
Reiki is an energy healing technique performed by systematic hand placement over 
specific body areas to facilitate energy flow for healing. A systematic review of RCTs showed 
that Reiki had moderate effects on pain among cancer patients and large effects among older 
adults (S. Thrane & Cohen, 2014). Reiki reduces pain and anxiety (medium to large effect 

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sizes) in children in palliative care (S. E. Thrane et al., 2016). An RCT among 80 participants 
with limited shoulder movement showed that energy healing techniques (Reconnective 
Healing and Reiki) were as effective as physical therapy in improving range of motion and pain 
(Baldwin et al., 2013). Given that Reiki demonstrated therapeutic benefit in symptom 
management with no reported side effects in multiple studies (Marcus, Blazek-O'Neill, & 
Kopar, 2013; Post-White et al., 2003; S. E. Thrane et al., 2016) and systematic reviews, it is 
included as a component of UZIT in this proposal. While the therapeutic benefit of Reiki is 
documented, Reiki application standardization is a challenge, and nonrandom selection of 
participants in these studies may limit the generalizability of the results. 
 
 
Essential oils, gentle movement/restorative poses, mindfulness, and Reiki, individually 
have demonstrated positive clinical outcomes. In two studies with non-significant results, 
intervention failures were attributed to challenges in treatment acceptance, adherence, or both 
(Kubo, Hung, & Ritterman, 2011; Ussher et al., 2014). Clearly, careful evaluation of treatment 
acceptance and adherence are critical in studies of mind-body integrative therapy. The unique 
contribution of the UZIT intervention to symptom science in chronic, debilitating illness is the 
potential synergy of combined modalities. To date, there have been no studies evaluating the 
4-component UZIT intervention in a systematic scientific approach. The only published study 
testing UZIT omitted the essential component of Reiki while introducing additional variables 
(e.g., remodeled environment and an audiovisual yoga education) that are not part of UZIT into 
the implementation (Kligler et al., 2011).  
 
This is an important foundational study to establish feasibility and acceptability and, 
potentially, to identify needed refinements, in integrative therapies for symptom management 
in complex chronic, life-limiting cardio-pulmonary disease. Once UZIT is established as 
feasible and acceptable for PH patients, future research will focus on testing the efficacy and 
effectiveness of UZIT to reduce symptom burden and promote HRQOL for persons with 
complex chronic, life-limiting cardio-pulmonary disease. Additional studies will include analysis 
of cost and health care utilization outcomes. The long-term goal of this program of research is 
to advance knowledge and evidence-based application of integrative therapies to manage 
symptoms and promote quality of life for persons with complex chronic, life-limiting 
cardiopulmonary conditions.  
 
III. Procedures  
    
  
A. Research Design  
 
This feasibility and acceptability study will use a pre/post intervention (6-weeks UZIT 
program) mixed-method design with repeated (weekly) measures of a single cohort of patients 
with PH. We will also explore preliminary efficacy testing to construct sample size estimates for 
future randomized control trials. Patients will serve as their controls.  
 
 
  
B. Sample  
 

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We will enroll 20 patients from two PH clinics within the Ohio State University Wexner 
Medical Center (OSUWMC). Patients with PH condition related to the cardiac cause are 
managed at the OSU Cardiology clinic located at the Ross Heart Hospital. Patients with PH 
condition related to other causes are managed at the OSU Pulmonary clinic at Martha 
Morehouse. These inter-professional clinics provide access to a patient population with diverse 
race/ ethnicity, sex, and age.  Overall, the OSUWMC PH Program manages approximately 
350 PH patients each year and receives referrals for 50 new patients per year. PH patients’ 
characteristics are similar to the U.S. data registry with a mean age of 55.8 years, 75% female, 
and 79% Caucasian. Patients at all stages of PH disease are followed for routine clinic 
appointments at 6-month intervals or more frequently if clinically indicated. Newly diagnosed 
patients are seen by PH specialists at 2-4 weeks interval for the first six months due to 
frequent monitoring and medication adjustments. All eligible patients managed at both PH 
clinics at OSUWMC will be invited to participate. Patients in both clinics receive standard 
medical treatments according to institutional and national clinical practice guidelines 
(McLaughlin et al., 2009; The Ohio State University Wexner Medical Center, 2014).  
 
Sample.  
 
Twenty convenience sample of community-dwelling adults with PH will be recruited for 
this study. Inclusion criteria are: 1) confirmed diagnosis of PH in the past, 2) age > 18 years, 
(children typically have different etiologies, and often require parent involvement in symptom 
management), 3) ability to ambulate independently, 4) New York Heart Association functional 
classification II/III, and 5) willingness to participate in the entire 6-8 weeks study.  Exclusion 
criteria are 1) known allergies to essential oils (lavender, lemon, or peppermint), 2) Asthma 
condition, 3) psychiatric illness requiring hospitalization within the last year per self-report or 
medical record, 4) self-reported pregnancy, 5) on-going participation in mind-body integrative 
therapy, and 6) inability to read/write English (to complete questionnaires).  
 
Sample Size and Statistical Power. 
 
 
 
The primary purposes of this study are to establish feasibility and acceptability of the 
UZIT intervention. A descriptive analysis will be applied. Pilot feasibility and acceptability 
studies of integrative behavioral approaches similar to the one proposed here generally 
include 6-19 participants (Cohen et al., 2007; Freedenberg, Thomas, & Friedmann, 2015; 
Lengacher et al., 2011; Palumbo, Wu, Shaner-McRae, Rambur, & McIntosh, 2012; Uebelacker 
et al., 2010; Yeh et al., 2010). With regards to preliminary efficacy outcomes of PH-related 
symptoms and PH-related HRQoL, we estimated statistical power.  Power analysis using two-
sided paired tests (t-tests for continuous and McNemar test for dichotomous/categorical 
outcomes) indicates that a sample size of 15 has sufficient power (≥0.8) to detect large effect 
size (standardized mean difference of 0.78 or greater for continuous outcomes; odds ratio of 7 
or greater for dichotomous/categorical outcomes, assuming that proportion of discordant pairs 
is o.6) with a significance level of 0.05. Therefore, small to medium effect sizes will not be 
detected as statistically significant in this study. As a pilot study to generate information on 
preliminary efficacy, we will not rely on statistical significance, but rather on clinical differences. 
Anticipating 10-15% attrition rate over a 6-8 week behavioral intervention study (Carter et al., 
2013; Grossman et al., 2010), we will enroll 20 participants to achieve a final minimum sample 
of 15.  

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C. Measurement / Instrumentation  
 
Table 1 outlines the data collection timeline. Participants will provide demographic data 
at enrollment. The PI’s preliminary work demonstrated that PH patients were able to complete 
four questionnaires in outpatient clinic settings within 15-minutes without undue burden. One 
hundred and eleven participants of 115 enrolled (96.5%) completed all four questionnaires 
without difficulty.  
Table 1: Data Collection Timeline 
Measurement 
Study 
AIMS 
Week 
0 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Week 
5 
Week 
6 
Consent 
  
X 
  
  
  
  
  
  
Demographics 
  
X 
  
  
  
  
  
  
UZIT 
Intervention 
  
  
X 
X 
X 
X 
X 
X 
Phone Call 
  
  
X 
X 
X 
X 
X 
X 
Diary Record 
2, 3b 
  
X 
X 
X 
X 
X 
X 
Field Notes  
2 
  
X 
X 
X 
X 
X 
X 
Debriefing (P) 
2 
 
 
 
X 
 
 
X 
Debriefing (I) 
2, F 
 
X 
X 
 
X 
X 
 
Session Video 
Recording 
2, F 
  
X 
X 
X 
X 
X 
X 
Acceptability 
Survey 
2 
  
  
  
  
  
  
X 
PAHSS 
3b 
  
X 
  
  
  
  
X 
Dyspnea, Pain, 
Fatigue, Anxiety 
3a 
  
X 
X 
X 
X 
X 
X 
Manipulation 
Check 
F 
 
 
 
 
 
X 
 
Enactment 
Check 
F 
 
 
 
 
 
X 
 
CAMPHOR 
3b 
  
X 
  
  
  
  
X 
 
Data Collection Instruments 
 
System Usability Scale (SUS, modified).  
 
This tool is comprised of 13 Likert Scale questions (1-7) capturing generic constructs 
about ease of use of a program (Table 8). Seven questions are positively worded, and six are 
negatively worded. Originally developed for assessment of new technologies (Brooke, 1986; 
Mc Lellan, Muddimer, & Peres, 2012), this tool was adapted to assess the acceptability of the 
UZIT program. Higher scores (7) indicate greater user ease and acceptability.  Since this tool 
is modified for assessment of UZIT program, psychometric properties (internal consistency) 

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will be assessed in this study population. Additionally, content validity will be determined to 
ensure that the measure represents all facets of acceptability construct. Two experts will judge 
each item regarding relevance, sufficiency, and clarity in representing the concepts underlying 
the measurement’s development using a list of behavioral objectives and definition of terms. 
Content validity index (CVI) will be calculated to represent an interrater agreement between 
experts. They will be asked to judge each item in Likert Scale of (1) not relevant, (2) somewhat 
relevant, (3) quite relevant, and (4) very relevant. CVI is equivalent to the proportion of items 
given a rating of 3 or 4 by both judges, which we expect to be 80% agreement or higher 
(Waltz, Strickland, & Lenz, 2010). This tool takes approximately 3 minutes to complete.  
 
Video-Recording.  
 
The study PI will set up the video recording equipment to capture therapeutic actions, 
verbal and non-verbal communications, and patient response during the UZIT session. 
Because some components are applied simultaneously (e.g. essential oil inhalation and gentle 
movement/restorative pose), video-recordings will provide comprehensive documentation of 
UZIT for fidelity monitoring and future detailed descriptive analysis.  
 
UZIT Session Field Notes & Debriefing. 
  
The study PI will observe and describe any relevant impressions during the UZIT 
session; and document semi-structured debriefing interviews at the end of the session with 
patients or therapist independently. Post session debriefing will be conducted with participants 
at the end of week #3 and week #6 and with interventionist at the end of other sessions (#1, 
#2, #4, and #5) to ensure adherence to the research protocol. Patients will be asked to rate 
their preference for each UZIT component (“like” most to least). Exit interview questions will be 
included at the end of UZIT program. 
  
Home Practice Diary. 
  
Participants will rate the intensity of dyspnea, pain, fatigue, and anxiety and record each 
UZIT modality used (Table 10). They will describe how they manage other symptoms and the 
amount of time (minutes) spent each day practicing each component. Participants will be 
reminded to complete diary entries using paper format prior to each UZIT session.  
 
Pulmonary Arterial Hypertension Symptoms Severity Scale (PAHSS). 
  
PAHSS is specifically designed to assess presence and intensity of 17 common 
symptoms identified from a sample of PAH patients (Matura et al., 2014), which respondents 
rate in severity from “0” to “10” (Table 11). This tool demonstrated construct validity with SF-36 
(α= .84) and the Profile of Mood States (α= .70). 
  
Cambridge Pulmonary Outcome Review (CAMPHOR). 
  
CAMPHOR is a 45 item, PH-specific quality of life tool that measures everyday 
experiences of PH patients. It measures multiple elements of each domain (symptoms, 
functional activities, and QOL perception) with simple and easy-to-understand phrasing (Table 

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12). The CAMPHOR demonstrated good internal consistency (Cronbach α= 0.90 – 0.92) and 
excellent test-retest correlation (r= 0.86-0.92) (McKenna et al., 2006), high sensitivity, 
specificity, and capacity to measure QOL change over time (Meads et al., 2008). Scores within 
each domain indicate patients’ perception of symptoms, functional ability, and QOL. This 
questionnaire takes approximately 10 minutes to complete. 
 
 
 
Modified Borg Dyspnea Scale (MBDS). 
 
Modified Borg Dyspnea Scale is a valid and reliable tool use in the clinical assessment 
of dyspnea symptoms for patients with cardiopulmonary conditions. MBDS is presented to 
participants to rate in a vertical format which indicates the ordinal scale ranges from “0” to “10” 
and accompanied by written descriptors representing the intensity of breathlessness (Table 
13).  The tool captures twelve levels of dyspnea because of the addition of “0.5” scale 
distinguishing level “0” = “nothing at all” and level “1” = “very slight”.  Modified Borg Dyspnea 
Scale is valid and highly correlates with physiologic indices among normal subjects (Wilson & 
Jones, 1989), patients with COPD (r = .91) (Mador et al., 1995), and emergency patients with 
COPD and asthma (Kendrick, Baxi, & Smith, 2000). It is reproducible and reliable for the 
measurement of breathlessness during exercise over extended study period (Wilson & Jones, 
1991). This tool takes approximately 1 minute to complete. 
 
Visual Analog Scale-Pain (VAS-P). 
 
Visual Analog Scale-Pain ranges from “0” = “no pain” to “10” = “worse pain possible”, in 
a 100 mm scale, presented in a vertical format (Table 14). Visual Analog Scale-Pain has test-
retest reliability among patients with acute pain in an emergency (r =.97) (Bijur, P et al, 2001), 
and among the general patient population (r = .94) (Hawker, Mian, Kendzerska, & French, 
2011). The tool is valid and correlates well with numeric rating scale tested among immediate 
post-operative patients (Delock, L et al, 1998; Ahlers et al., 2008) and was simple to use by 
ICU patients (Ahlers et al., 2008). This tool takes approximately 1 minute to complete. 
 
Visual Analog Scale-Anxiety (VAS-A). 
  
Visual Analog Scale-Anxiety scale ranges from “0” = “not anxious at all” to “10” = “most 
anxious ever”, in a 100 mm scale, presented in a vertical format (Table 15). Visual Analog 
Scale-Anxiety instrument correlate with the Spielberger State Anxiety Inventory (r = .50) 
(Chlan, L. 2004; Facco, E et al, 2015).  It is less burdensome to complete and was shown to 
be an excellent tool for use among ICU patients (L. Chlan & Savik, 2011; L. L. Chlan, 2004; 
Elliott, 1993). 
   
Visual Analog Scale-Fatigue (VAS-F). 
  
Visual Analog Scale-Fatigue scale ranges from “0” = “not tire at all” to “100” = “the most 
tire I’ve ever been”, in a 100 mm scale, presented in a vertical format (Table 15). The original 
18-items (physical and emotional dimensions of fatigue) fatigue instrument has documented 
validity and reliability (K. A. Lee, Hicks, & Nino-Murcia, 1991). The single item VAS-F 

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instrument was shown to correlate well (r = .80) with the fatigue subscale of POMS among 
end-stage-renal disease patients (Brunier & Graydon, 1996).  The VAS-F was compared to an 
11-item numeric rating scales (NRS) among patients with idiopathic chronic fatigue and 
healthy adults and found capture the fatigue severity in similar manner; the NRS and VAS-F 
scores were approximately 2.7 time higher in patients compared to healthy adults (N. H. Lee & 
Son, 2012). The single item VAS-F instrument is demonstrated to be practical for use in 
critically ill mechanically ventilated patients in intensive care unit (L. L. Chlan & Savik, 2015). 
 
 
 
 
Manipulation Check Questions. 
  
As an important part of intervention fidelity check, manipulation check will be conducted 
to ensure that participants retain the knowledge and skills relevant to UZIT training. These 5 
multiple choice questions will include the content regarding essential oil use, gentle body 
movement, body-guided meditation, and Reiki therapy. This manipulation check will be 
completed at the end of session #5.  
 
 
 
Enactment Check Questions. 
  
As an important part of intervention fidelity check, enactment check will be conducted to 
determine the concordance between participant’s and interventionist’s perception with regards 
to the knowledge and proficiency level about UZIT training. These 2 multiple choice questions 
ask both participant and interventionist to rate in a Likert scale from 0 to 7 to the level of 
competency and proficiency about UZIT practice. This enactment check will be completed at 
the end of session #5. 
 
UZIT Interventionists Focus Interview Questionnaire. 
 
The UZIT Interventionists questionnaire will also solicit interventionists’ perception 
about UZIT feasibility, patients’ acceptability of UZIT intervention, and UZIT fidelity. Because 
interventionists had been closely involved in the creation and refinement of the UZIT 
intervention protocol and fidelity training throughout the course of study period, series of 
questions in this questionnaire will include these 3 aspects of query (please see attached). 
Interventionists’ audio recorded comments will be transcribed verbatim, coded and categorized 
for common themes using NViVo qualitative data analysis program. 
 
  
  
  
D. Detailed study procedures  
 
 
Intervention. 
  

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Individual, one-to-one UZIT sessions will be delivered by experienced therapists who 
are trained and certified in UZIT curriculum and training protocol (4 months coursework + 6-8 
hours/week practice+50 hours clinical practicum). Individual rather than group intervention 
delivery reduces distractions and the social influences of a peer group. Private UZIT sessions 
are also more conducive to tailored treatment and allow for a more accurate symptoms query. 
A competency check-off list will be required of all UZIT interventionists before delivering study 
intervention. At least two experienced, UZIT-trained therapists will be trained in the study 
intervention delivery according to the research protocol. Sessions will be arranged at a 
convenient time for patient and therapist and conducted at the OSU Integrative Medicine 
outpatient facility in Columbus, Ohio. The facility is easily accessible and conveniently located 
close to the main medical facility; parking is free. Patients will participate in a total of 6 visits 
lasting approximately 1 to 1.5 hours per visit to be scheduled within an 8-week period. 
Participants will receive an incentive of $30.00 in gift certificates for the entire study, distributed 
in $5 increments at the end of each visit. This amount is considered reasonable because the 
study intervention (personal UZIT sessions) has an estimated market value of $100.00 per 
session and will be provided at no cost to participants. 
 
 We received UZIT therapist recommendations and rationale for proper intervention 
sequence. Our UZIT study session will include the following procedures. After a brief 
introduction, the therapist will inquire about bothersome symptoms. The session will include 
essential oil inhalation, gentle movements/restorative pose, body-awareness meditation, and 
Reiki. A guided breath awareness exercise will be synchronized with body movement. 
Participants will practice body-awareness meditation by focusing on the therapist’s guided 
instruction on how to bring awareness to bodily sensation. Specific instruction and 
demonstration will be provided for an appropriate restorative pose using a yoga mat, bolster, 
blankets, and gentle weights (1-3 lbs) (Yee, 2004). The therapist may assist the participant in 
comfortable positioning and will apply each modality within a specified time frame. At the end 
of the session, participants will receive a personalized recommendation for appropriate gentle 
movement/restorative poses and samples of essential oil for home practice. Interventionist’s 
behaviors will be monitored via direct observation, review of video and audio recordings to 
ensure intervention dose delivery (Wyatt, Sikorskii, Rahbar, Victorson, & Adams, 2010). 
  
Study intervention fidelity will be ensured in the following ways: (1) therapists will 
achieve initial competency training in adherence to the research protocol at 80% compliance 
rate (Gearing et al., 2011); (2) intervention implementation adherence will be monitored via 
direct (but remote) video observation of each session with 25% of video recordings (n=30) 
receiving detailed review. Although the principal investigator (PI) will review each UZIT 
session, the Hawthorne effect will be minimized by the use of remote video recording. We will 
audit therapist’s intervention delivery using a pre-determined checklist to validate dose delivery 
and detect any drift warranting therapist retraining. To enhance patient adherence, participants 
will receive weekly appointment and practice reminders via phone calls/text messages. 
  
Recruitment. 
  
Study participants will be recruited in the following ways: (1) patient response to a 
recommendation by their clinicians; (2) patient response to a posted study advertisement; (3) 
patient response through a secure NIH-sponsored volunteer registry (ResearchMatch) 

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available through the OSU Center for Clinical and Translational Science; or (4) patients with 
confirmed PH diagnosis will be screened by clinic staff during routine PH clinic visits for 
potential study eligibility. When PH clinic patients are identified as potentially eligible, clinic 
staff will provide a study brochure and inquire whether the patient would like to learn more 
about the study. If a patient indicates interest in the study, s/he will be approached by the 
study PI for consent. Clinic staff will follow a verbal script in seeking patients’ interest. 
Research staff will follow a verbal script in describing general information about the study. The 
consenting process will include further discussion about the study protocol and participation 
including risks and benefits with sufficient time to address all questions. After consent, the 
initial study visit will be scheduled.  
 
 
Potential Risks. 
 
A foreseeable potential risk to research participants is a possible allergic reaction to 
inhalation of essential oil during the UZIT session, which is considered to be rare, a minimum 
risk. UZIT has been provided to more than 900 hospitalized patients at the OSUWMC without 
any demonstrated reactions to these three essential oils (Beth Steinberg, personal 
communication). There is no known evidence that essential oils interact with PH medications 
that participants may be taking. Using essential oil in patients with PH, we will take into 
consideration the following safety risks. PH patients with comorbidity of asthma condition may 
respond to essential oil inhalation with some airway reactivity. “Rarely, essential oils can cause 
respiratory irritation, rash, asthma, or headaches. People with severe asthma who are 
sensitive to aromatic triggers should be cautious about using aromatherapy. Some people are 
more sensitive to synthetic chemical fragrances than essential oils derived directly from 
plants.”98  In this study protocol, we will use high purity therapeutic grade essential oil derived 
directly from plants provided by Young Living, Inc., which is less likely to cause this reaction 
even among asthmatic patients. In adherence to the OSUWMC Aromatherapy Practice 
Protocol, the oil will be introduced slowly accompanied by continuous observation and 
monitoring of patient’s response. We will place 1-3 drops of essential oil on a small cotton pad 
and put on the outside of patient’s clothing not in direct contact with the skin in the upper chest 
area approximately 1 inch away from the nose. Patient’s body heat and breath inhalation will 
facilitate the oil delivery slowly through the nose. Nursing staff or other licensed health 
professional staff who provide documentation of having completed an approved training on 
aromatherapy may supervise, use, or instruct staff/patient/family in the use of essential oils for 
increased comfort and symptom management. The study PI has completed this required 
educational training that included: 1) History/background of the use of essential oils in 
healthcare; 2) Clinical indications/research support for use of essential oils in healthcare 3) 
Proper application/controlled use of essential oils, and 4) Safety considerations, risks, allergic 
reactions, and contraindications associated with the use of essential oils. https://herbs-
supplements.osu.edu/ 
 
Also, patients who require continuous oxygen use (with its associated airway “drying” 
effect) may report further discomfort to essential oil inhalation. For patients who currently use 
inhaled prostacyclin (Ventavis® or Tyvasso®), there is a potential risk that essential oil 
inhalation may have an added “drying” effect on the respiratory mucosa. Essential oil is non-

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combustible and is safe for use while patients receiving oxygen. Furthermore, essential oil in 
this delivery method have been applied safely to ICU patients on mechanical ventilators.  
 
We will limit the use of essential oil to the most frequently used and well-tolerated 
scents (Lavender, Lemon, and Peppermint) to reduce this likelihood. As a part of current 
practice, these three essential oils are being used in hospitalized patients at the OSUWMC 
with no adverse incidence to date after approximately 900 applications (Beth Steinberg, 
personal communication). Patients who have known allergy or reactions to essential oil will be 
excluded from this study.  
 
There is an extremely unlikely possibility that persons with PH may experience some 
changes in hemodynamic status related to position change during UZIT practice. Although 
these changes have been documented during routine exercise, it is less likely to occur with 
UZIT practice. UZIT is not an exercise routine but rather a gentle, slow, and gradual position 
change that excludes any contraindicated positions. Despite the fact that yoga practice is 
encouraged for persons with PH, patients are cautioned not to assume “bending over” or 
“reaching overhead” postures due to the risk of a sudden drop in cardiac output. 
(“Exercise/Yoga/Tai Chi –What can be done & what to avoid”, 2012 Pulmonary Hypertension 
Association Conference Webinar) www.PHAasociation.org (Accessed, 1/13/16). A 
comparative study evaluating possible mechanism for hemodynamic changes during exercise 
between COPD patients with or without PH reveals the following differences. Because of 
existing high pulmonary pressure, stroke volume change (increase) as a response to exercise 
is compromised in patients with PH leading to reduced cardiac output.2 Given this impaired 
compensating mechanism, we must take extra precaution when participants change position 
from lying down to sitting and to standing abruptly. PH clinicians encourage patients to be 
active by participating in moderate exercise and integrative practice (yoga, Tai Chi, 
mindfulness practice). Strong emphasis is made to avoid bending over positions and the 
importance of “breathing through activities”, and “pay attention to your body” (“Breathing your 
way calm” and “Exercising mindfully with PH” www.PHAasociation.org (Accessed, 1/13/16). 
Therefore, UZIT can be an important adjunctive approach due to its incorporation of body-
awareness meditation to ascertain the physical capability that is safe for patients.  
 
We will provide all UZIT sessions at the CIHW outpatient clinic located at 2000 Kenny 
Road, Columbus, Ohio. As a part of the OSUWMC, this outpatient facility is equipped with 
quick access to emergency medical equipment (Resuscitation Cart).The applicant/PI is an 
experienced ICU nurse, trained in Advanced Cardiovascular Life Support (ACLS) protocol, and 
very familiar with emergency response system within the OSUWMC campus. The applicant/PI 
will be present at all visits to monitor study intervention, collect data, and assist UZIT therapist 
if an emergency situation were to occur. The CIHW is located close (< 5 min) to the OSUWMC 
emergency department. 
 
There is also a potential risk of emotional distress to participants when answering 
survey questions about symptoms or feelings. Although unlikely, participants may experience 
feelings of anxiety, depression, and symptoms. In such a scenario, every attempt will be made 
to allow participants to rest and re-focus while providing emotional support. If needed, 
participants will be referred to psychologist/social work counselors available within the 
OSUWMC. In a situation of severe emotional distress, participants may be taken to an 

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emergency department through a 911 system. Questionnaires included in this research study 
are standardized tools that have been used in previous research conducted by the PI with 115 
patients with PH without untoward effect on subjects’ emotional state. Fatigue is possible when 
answering questions from a battery of questionnaires. We will provide rests or breaks if 
needed or will terminate a data collection session if the patient becomes too tired, upset or 
unable to continue. In a situation of minor physical distress/discomfort, we will provide 
continuous monitoring while allowing participant sufficient time to rest. If there is severe 
physical distress, participants may be taken to an emergency department through the 911 
system.  Appropriate Adverse Event reporting will be filed according to the IRB guideline and 
will be evaluated by the Data Safety and Monitoring Board of the study (below). As in all 
research, there is a potential for loss of confidentiality.  
 
 
 
 
Protection against Risk (Confidentiality of Data and Computer Records).  
  
Confidentiality will be protected through the use of study identification numbers that will 
be kept separate from personal identifiers. All study documents will be kept in designated 
locked file cabinets in the Center of Excellence in Critical and Complex Care Research Office 
at the College of Nursing. All study materials will identify participants solely by the assigned 
code numbers. The following steps will be taken to protect the confidentiality of all data and 
computer records: 
 
• Identification codes rather than names will be used on all source documents   
• The identifiers linking identification codes with individual names are only available to the 
project PI, and Primary Sponsor and stored in password-protected, encrypted file. 
• Completed questionnaires will be collected by the researcher immediately in a sealed 
envelope for proper storage.  
• Paper data collection forms will be stored in a locked file cabinet, and only researchers 
involved in the study have access. 
• Electronic data files will be stored in a file folder that is dedicated to this project only and 
not linked to any public servers.  Secured access to the research file folders will be 
limited to those study personnel directly responsible for analyzes and managing data.  
The computer and data files will be encrypted, and password protected. Participants’ 
identification will be de-identified according to the College of Nursing de-identification 
standard using a study identification code for the subjects stored (keys) by encrypting 
them in a separate place/folder. All data will be housed on the College of Nursing’s 
secure file storage server for research projects. The research server runs Windows 
Server 2012R2 Enterprise and is only used to host research files. No unnecessary 
services are running including no IIS, SQL, MS Office, and FTP. The Windows 
operating system is kept up to date by weekly, automatic updates from Microsoft. The 
physical server is housed in a secure room within Newton Hall. Only pertinent IT staff 
and the building coordinator have keys to access this room. The College’s data center 
is also equipped with a video surveillance system that alerts IT personnel when 
someone accesses the room. Electronic access to the research server is restricted to 
the college LAN or VPN by a Cisco ASA firewall. Access from the Internet without VPN 

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is not allowed. Electronic access is further restricted by the on-host Windows Firewall, 
and User access is tightly controlled, by request only. Permissions are audited annually 
by IT in collaboration with the folder/study owner. All user accounts connecting to the 
server are domain accounts and are authenticated through a domain controller. User 
access and system information are also logged and exported to a central event logging 
server. 
• For the video recording, a Foscam surveillance camera with a built-in microphone will 
be placed in a discrete location in the room. It will be connected to a computer directly 
with a network cable and will not be on the internet. The recording will be saved 
temporarily on the computer (encrypted and password-protected) and then deleted after 
being transferred to the secure research folder via a secure server within 24 hours after 
the recording session. The video recording data files will be uploaded to a secure 
access research file folder at the conclusion of each UZIT recording. The file folder is 
dedicated to this project and not linked to any public servers. Secured access to the 
temporary data file and video recording research data files will be limited to those study 
personnel directly responsible for analyzes and managing data. The computer and 
video data files will be encrypted, and password-protected. If/when participants 
withdraw from study participation, their video recording will be deleted. These 
procedures are consistent with methods previously used by the study Sponsor (Dr. 
Happ) and best practice in video recording for research.99  
 
Potential Benefits of the Proposed Research to the Participants and Others. 
 
Potential immediate benefits of participating in this research are the possible benefits of 
positive feelings and health benefits associated with relaxation and personal attention provided 
by therapist and research personnel. Additionally, learning how to be more aware of one’s 
body sensation can have the potential benefit of effective physical tolerance and emotion 
regulation. However, no benefit to participants can be guaranteed. Knowledge gained from this 
study (acceptability of the treatment and its practical use) will extend its future application to 
larger patient population groups. Scientific evidence documenting UZIT’s therapeutic impact 
on cardiopulmonary symptoms, and anxiety may provide valuable knowledge about patients’ 
ability to self-manage and adhere to PH treatments. Furthermore, this early phase evidence 
can provide foundational data for future studies in identifying acceptability requirements and 
barriers of UZIT. Subsequently, efficacy testing can be carried out in patients with PH and 
other chronic disease conditions. 
 
  
  
D. Internal Validity 
  
The primary threat to internal validity is intervention fidelity which is a major concern in 
behavioral intervention research using multi-component mind-body integrative. As previously 
described, we identified specific ways to ensure intervention dose, intervention delivery, 
intervention receipt, and intervention enactment to avoid study bias. Study interventionists will 
be trained according to the intervention protocol and their competency will be checked at the 
initiation of the study as well as throughout the study period. Their delivery method and dose 
will be checked against a pre-defined fidelity checks through video recording review. Post-
UZIT session debriefing with interventionists will provide an on-going quality assurance check 

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making sure that there is no drift in study implementation procedure. Intervention receipt and 
enactment will be checked by using manipulation checks and enactment checks questions. 
  
E. Data Analysis  
 
Descriptive statistics (mean and standard deviation (SD) for continuous variables and 
frequency and percentage for categorical variables) will be used to describe relevant 
demographics and clinical characteristics of the sample such as sex, gender, NYHA 
classification, and education level.  
 
Aim 1: To determine the feasibility of a 6-week UZIT intervention in community-
dwelling adults with PH.  
Feasibility will be evaluated by recruitment and retention rates. Recruitment rate will be 
determined by 1) proportion of patients approached who consent to the study, and 2) length of 
time (months) required to recruit 20 subjects.  Retention rate will be calculated as the 
proportion (completed/enrolled) of participants remaining to study completion. UZIT Session 
Video Recording: In addition to fidelity monitoring of initial 30 recordings, subsequent 30 
recordings (total of 60 or 50%) will be randomly selected for quality/intervention fidelity audit 
using a checklist tool with the expected 80% protocol adherence level. 
 
Aim 2:  To determine the acceptability of UZIT among community-dwelling adults 
with PH for symptom management.  Sub-aim (2A): to determine what components of the 
UZIT program are preferred by adults with PH.  
Acceptability: Acceptability scores will be calculated from participants’ responses to the 
SUS. Composite means and standard deviations will be computed for each item. An average 
of the total SUS scores for the sample (mean, SD) will be calculated. Field Notes: Semi-
structured observation notes with free-text narrative will be transcribed, coded, formatted, and 
refined into qualitative themes regarding participant perceptions of the therapy, their practice of 
UZIT components, and symptom experience. Patients’ preference rating of each UZIT 
component will be tabulated. UZIT Attendance: We will compute the number of sessions 
attended and completed per participant and for the total sample by range, median, mean and 
mean proportion. Home Practice Diary: Participants’ written responses to questions on 
strategies for symptom self-management will be transcribed, coded, formatted, and refined into 
qualitative themes using basic qualitative description.(Miles, Miles, A Michael Matthew B, & 
Huberman, 1994). We will review the first participant’s diary, develop a coding list and 
definitions, review and discuss with Sponsor in weekly analytic sessions using the constant 
comparison of subsequent diary entries. A stem-leaf diagram will be used to identify common 
themes. Participants’ daily symptom ratings, the length of UZIT home practice time 
(minutes/day) will be analyzed descriptively (range, mean, SD, median, mode).  Although self-
reported health diary data collection method has potential limitations such as inaccurate and/or 
incomplete data (L. E. Burke et al., 2008; Stone, Shiffman, Schwartz, Broderick, & Hufford, 
2003), it is suitable for use in this limited budget research proposal for the following reasons: 
ease of transport, ease of use, and is already a routine practice for patients with PH. Since this 
pilot study does not require precise time recording of certain activity (e.g., food intake time and 
amount), extensive data content entry, and does not extend beyond 6-8 weeks, we plan to use 
a simple paper and pencil health diary, rather than electronic data capture and to maintain 
participants’ interest and motivation in this data collection with clear expectations and 

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emphasis of the importance of obtaining this data (Green, Rafaeli, Bolger, Shrout, & Reis, 
2006). 
Aim 3:  To explore the preliminary efficacy of UZIT. 
Aim 3A: To explore the preliminary efficacy of weekly UZIT sessions on dyspnea, 
pain, fatigue, and anxiety. Symptoms of dyspnea, pain, fatigue, and anxiety (symptom 
intensity) will be assessed in response to each UZIT session. We will plot the weekly visit 
rating of symptoms (dyspnea, pain, fatigue and anxiety) trajectory pattern from week 1 through 
week 6 for each participant and by biological variables (e.g. age groups, sex, and NYHA 
classification). Mixed effect modeling for repeated measures will be used to model the change 
over time. Estimates derived from mixed effect modeling will be more accurate by accounting 
for within-subject correlation. It also has the advantage of the most efficient use of data. 
Estimates are derived from all available data, not just data from completers.  
 
Aim 3B: To explore the preliminary efficacy of 6-week UZIT program on PH-relate 
symptoms and HRQoL. We will compare pre-and post-differences in composite symptoms’ 
presence and severity (PAHSS) and HRQoL (CAMPHOR domains) using McNemar tests for 
paired proportions and dependent t-tests for paired means. As a pilot study to generate 
information on preliminary efficacy, we will rely on clinical differences. The point estimates and 
effect sizes from this pilot study will guide the sample size calculation for future larger scale 
study (efficacy and effectiveness). We will primarily report summary statistics on proportions 
and 95% confidence intervals at each time point. We will also determine the correlation 
between changes in PAHSS and CAMPHOR scores with a dose of home practice 
(minutes/week) to indicate a dose-effect relationship. Furthermore, the frequency and the 
amount of home practice can serve as an indicator of participants’ acceptability of the UZIT 
program. 
  
IV. Bibliography  
Include a reference list of literature cited to support the protocol statement.