Pilot Study of Group Video Yogic Breathing App in Breast Cancer Survivors
Phase: NA
Conditions: Breast Cancer
Sponsor: Medical University of South Carolina

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PROTOCOL TITLE: 
Pilot study of group video Yogic breathing app in breast cancer survivors 
 
PRINCIPAL INVESTIGATOR: 
Dr. Sundar Balasubramanian, PranaScience Institute LLC 
 
NCT05161260 
 
 
Formatted: Indent: Left:  0"

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1.0 
Objectives / Specific Aims 
• 
The overall objective of the proposal is to develop and test a mobile application that 
will help cancer survivors to practice breathing exercises for their symptom 
management. Development of a mobile application to deliver the breathing exercise 
or the attention control intervention would be accomplished as a first step by 
PranaScience Institute and would not require IRB approval. 
• 
Specific Aim : Pilot test the mobile application for feasibility, acceptance and 
symptom management in breast cancer patients that underwent radiation treatment 
within the past 2 months While the app will be ultimately used widely at all stages of 
cancer treatment and survivorship, in order to reduce variabilities, the current study is 
focused on breast cancer in this pilot study. Results from this study will inform 
designing larger future clinical trials in broader cancer patient population.  
• 
 
2.0 
Background 
Cancer survivorship is associated with long-term chronic medical issues.  
Cancer is the second leading cause of death in the US, with breast cancer being the most predominant 
type for cancer in women(1). Due to improvements in early diagnosis and treatment, the number of cancer 
survivors in the U.S. has steadily increased(1). Approximately 90 percent of those diagnosed with breast 
cancer now survive five years after diagnosis. For instance, in 2019, there are more than 3.8 million breast 
cancer survivors in the US(2). As cancer becomes a chronic condition rather than a life-threatening illness, 
the health care community must learn to recognize and manage the long-term sequelae of physical and 
psychological side effects of treatment protocols. Major issues receiving the most attention include chronic 
inflammation(3, 4), increased risk of second primary malignancies(5), pain and muscle weakness(6), 
depression and anxiety(7-10), fatigue(11), sleep disturbance(12), dryness of the mouth(13, 14), and less 
threatening medical conditions. In addition, preexisting comorbidities such as obesity, hypertension, 
hyperlipidemia, and diabetes will most certainly affect disease-free survival, and ultimately, overall 
survival(15). For example, breast cancer survivors are at significantly higher risk for developing anxiety 
and depression compared to women who do not have breast cancer(16-19). Managing these symptoms 
is essential, as mortality rates were 39 times higher in patients who had been diagnosed with major 
depression(7), and a decrease in depression symptoms was associated with longer survival in metastatic 
breast cancer patients(20). As a result of this changing landscape, survivorship care programs provide a 
critical component of the patient treatment pathway. Looking at improving and sustaining long-term 
survival in cancer requires a total-health strategy that includes a focus on non-pharmacological 
lifestyle and mind/body interventions. 
  
 
3.0 
Intervention to be studied  
Intervention Type 
Name 
Description 
Behavioral (e.g., 
Psychotherapy, Lifestyle 
Counseling); 
Pranayama-based group 
video app for yogic 
breathing 
The YB app (alpha 
version) will be a first 
production version of a 
Yogic Breathing mobile 
app that guides users 
through proscribed YB 
exercises version and 
contains special 
features designed to 
measure compliance and 

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Intervention Type 
Name 
Description 
capture feedback from 
the user in the Phase I 
program. 
Behavioral (e.g., 
Psychotherapy, Lifestyle 
Counseling); 
Attention Control app 
feature 
An Attention Control 
(AC) mode will be 
integrated into the app 
so that users can 
operate the app in AC 
mode instead of YB. "AC 
mode" will be visually 
and functionally similar 
to the YB mode to avoid 
variability due to 
different user 
experiences. In place of 
the YB session, there 
will be a similar 
session providing 
instruction on an AC 
activity, which will be 
presented to the user as 
a "mindfulness 
practice". This will 
serve as a control for 
YB and will not be 
carried into the 
commercial version(s) of 
the app. 
 
Group video practice app for peer-supported home-based practice of Yogic breathing. 
Complementary and integrative health approaches are increasingly being used by cancer patients and 
survivors to manage symptoms that do not always respond to pharmacological interventions, such as 
stress, mood, and fatigue(21). In this regard, yoga therapy, which encompasses a constellation of mind-
body practices including meditation, physical exercises or postures, and breath control, has emerged as a 
valuable complementary therapy for cancer patients and survivors(22-29). Yogic breathing (YB or 
pranayama) consists of a collection of techniques used to voluntarily regulate breathing without the need 
of physical exertion(30). YB induces a strong relaxation response via vagal and other parasympathetic 
stimulation(31, 32) which has been causally linked to genes involved in the inflammation, stress response, 
metabolism, and tumor suppression(33-36). Dr. Sundar Balasubramanian, a global leader in the biology of 
yoga and PI of this proposal, has independently demonstrated that YB stimulates 1) reductions in levels of 
salivary pro-inflammatory biomarkers(37), 2) induction of the neuromodulator Nerve Growth Factor 
(NGF), which is important for maintenance and survival of the peripheral and central nervous system(38), 
and 3) alterations in the levels of proteins associated with tumor suppression and immune regulation(39). 
Although mobile Apps provide a convenient way to provide mindfulness exercises and could reduce 
barriers of delivery intervention(40-42), adherence to such apps is at very low rates (43, 44).  However, 
sustained practice of yoga (45) alongside other behavioral interventions (diet, exercise) are considered 
feasible, acceptable, and successful through peer support where the participants motivate each other for 
enhanced adherence, and improved outcomes(46, 47). Peer support is recognized an effective framework 
for sustained adherence to interventions in cancer(48-51). In this context, we envisaged that group video 

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chat apps(52, 53) could provide a unique opportunity to deliver YB interventions for simultaneous 
practice by participants in virtual groups. While additional work is needed to demonstrate the efficacy of 
specific mind-body approaches in improving health outcomes for cancer survivors, there is clear 
opportunity for the development of new tools that promote and facilitate acceptable, feasible, and 
sustainable mind-body intervention strategies that serve to improve overall wellbeing. To this end, Dr. 
Balasubramanian founded PranaScience Institute to develop optimized YB methods and materials that can 
be delivered directly to survivors in their home. The goal of this Small Business Technology Transfer 
Research (STTR) project funded to PranaScience by the National Institutes of Health (NIH) is to develop 
an app for group video practice of YB that is optimized for home-based delivery of YB programs and 
maximally effective in reducing symptomatic conditions associated with cancer treatment and survival. 
For the Phase I portion of this project, PranaScience will build a prototype mobile app and test the app for 
adherence, feasibility, and acceptability to support symptom management in a pilot study of breast cancer 
survivors in collaboration with the Medical University of South Carolina (MUSC) and a mobile 
technology firm. 
 
Preliminary Studies 
YB alters salivary proteome. The molecular 
mechanisms of YB in isolation have not been studied 
in detail(54), and there are currently no established 
protein biomarkers that can be used to evaluate the 
effects of YB on clinical outcomes or wellbeing. 
Saliva is an easily accessible source of biological 
material that can be used to assay biomarkers in a 
non-invasive manner(55-58). Further, salivation is 
one of the parasympathetic activation responses(59); 
thus, Dr. Balasubramanian hypothesized that a 
proteomic survey of saliva following YB may reveal 
proteins that are altered in response to YB. Twenty 
healthy volunteers were randomized to a YB or 
Attention Control (AC) group in collaboration with a 
biostatistician to ensure equal gender distribution. 
YB participants were tested one-on-one with a yoga 
instructor who taught participants how to perform 
YB, which included two phases, namely, Chanting 
Om and Thirumoolar Pranayamam (TMP), each for 
10 min (Fig. 1). AC participants were guided to 
perform quiet reading for 20 min in a seated position 
in presence of yoga instructor. Saliva samples were 
collected from participants in both groups at 0, 5, 10, 
15, and 20 min. Protein was extracted and quantified 
from saliva samples and 100 g analyzed by LC-
MS/MS to identify differences in protein 
composition driven by YB. Comparison of proteins 
following YB or AC using a normalized spectral 
counting approach revealed significant increases in a number of proteins involved in immune response 
and tumor suppression including deleted in malignant brain tumor 1 (DMBT1), which has been shown to 
be downregulated in many cancers(60), and IGLC2, which is known to be increased during viral infection 
and thought to play a role in immune response(61, 62).  Targeted western blots were used to validate these 
findings (Fig. 2, and Balasubramanian et al.(39)). These findings represent the first demonstration that 
YB induces changes in biomarkers of immune response and cancer. 
 
Figure 1. YB study design. During TMP, participants 
are guided to a) close right nostril and inhale through 
left nostril for 2-count, b) close both nostrils and retain 
breath for 8-count, c) open right nostril and exhale for 
4-count. This cycle is repeated for 10 min. 
 
Figure 2. Pooled densitometry data of DMBT1 
Western blots. *, p<0.05 YB vs AC for that 
timepoint; #, p<0.05 YB timepoint vs baseline. 

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YB reduces 
levels of pro-
inflammatory 
proteins. Yoga 
practices are 
widely 
perceived to be 
stress-reducing; 
however, the 
molecular 
mechanisms for 
how yoga 
practices such as 
YB affect stress 
response are 
lacking. In a 
study of twenty 
healthy 
volunteers stratified by gender into a YB or AC group (n=10 per group), Dr. Balasubramanian examined 
the effects of YB on levels of salivary cytokines. As in the aforementioned study, enrolled participants 
performed a 20 min YB or AC intervention one-on-one with a trained instructor and salivary samples 
were collected at 5 min intervals from both groups. Cytokine multiplex assays were performed on the 
samples to look at ten stress-related cytokines (IL-1, IL-1A, IL-6, IL-8, IL-10, IL-17, IP-10, MCP-1, 
MIP-1b, and TNF-alpha). Levels of the cytokines IL-1, IL-8, and MCP-1 were significantly lower in the 
YB group (Fig. 3). IL-1 is implicated in stress, inflammation and pain perception(63, 64), and is 
currently being pursued as a clinical target for autoinflammatory syndromes(65). IL-8 is a key mediator of 
inflammatory processes during various disease conditions involving oxidative stress; elevated levels of 
IL-8 are associated with poor prognosis in breast cancer(66). There are currently no therapies that directly 
target IL-8. MCP-1 is elevated and secreted in response to chronic inflammation and is a biomarker for 
coronary heart disease(67). These early studies, though correlative, provide the first evidence that 
breath regulation, even for short periods of time, have potential to induce measurable changes in 
biological functions related to stress response and inflammation. 
YB in-person group practice is an acceptable and feasible intervention for cancer patients and 
caregivers. To evaluate whether cancer patients and their caregivers would be receptive to a YB program 
for symptom relief and support, the PI conducted a pilot study at the American Cancer Society Hope 
 
Figure 3. Heat maps illustrating reduction in levels of key cytokines over 20 min of YB. Samples 
(n=2 replicates per timepoint) analyzed using a Multiplex ELISA assay (Bio-Plex Pro). 
Table 1. In-person group YB program feedback 
Theme 
Exemplary Quotes from Participants 
Program Implication 
Logistics 
• Longer time/duration for discussion.  
• Maybe 10 minutes longer. Will do me good.  
Extend session length. 
Marketing  
• More advertisement about the class and how it 
helps. 
• Maybe work on the name of the class to get more 
people to participate. 
Develop program materials 
with details about the purpose 
and previous patients’ 
experiences. 
Resources • Possibly printed material on breathing technique. 
• Have a one page summary of the exercises to 
take with us. 
• Provide handouts of exercises and web site. 
Develop and distribute 
program toolkit to participants 
to promote technique 
adherence and practice. 
Program 
impact 
• Wonderful, gained knowledge and techniques to 
improve my mental and physical health. 
• Please keep up the work you do to help us 
improve ourselves thank you.  
Engage cancer patients and 
caregivers to develop 
program description and 
messaging. 

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Lodge in Charleston, SC over a 9-month period. The Hope Lodge facility provides temporary housing to 
cancer patients and caregivers that are receiving treatment at a nearby cancer treatment facility. Guests 
were recruited to participate in a YB class consisting of 20 minutes of YB exercises. For each class, a 
certified yoga instructor provided demonstration and verbal instruction for five different YB exercises to a 
group of 2-5 participants. At completion of the class, participants were surveyed via a voluntary 
questionnaire to assess sociodemographic (age, gender) and clinical (cancer type) characteristics, 
perceived and experienced YB benefits (mood, pain, appetite, among others), and likelihood of the patient 
practicing these methods in the future. Responses to open-ended questions were reviewed using a group 
process to identify themes. Patients of all cancer types attended classes at rates comparable to control 
caregivers with head and neck cancer patients participating most frequently (27.8%), followed by breast 
(13%) and brain cancer (9.3%). No adverse effects were reported by any of the patients. All participants 
were very (90%) or somewhat (10%) satisfied with the experience, with the majority comfortable with the 
session length (83% reported length was “just right”; 17% reported “too short”). Most participants (83%) 
reported that they would continue to do exercises at home. Majority of participants indicated that they 
would be very (46%) or somewhat (40%) interested in participating in a longer program if offered at a 
convenient location. Self-reported measures collected from participants indicated perceived 
improvements in stress, pain, and mood after a single YB group session. Open-ended comments from 
participants highlighted some general themes focused on impact, logistics, resources/ marketing (Table 
1). Additional data specifically from women with breast cancer (Survivors’ Fit Club, a 10 wk group 
program) reflected similar self-reported and thematic outcomes (Support letters from two breast cancer 
survivors who attended the YB sessions are attached). Overall, cancer survivors rated YB experiences 
favorably and expressed enthusiasm for continued practice if given the appropriate resources. Finally, 
PranaScience has been a leader in providing group video YB sessions via Zoom app for various target 
audiences since the year 2018.  
  
 
4.0 
Study Endpoints  
Type 
Name 
Time 
Frame 
Brief Description 
Primary; 
Adherence 
12 
weeks 
Adherence will be evaluated by assessing total practice times 
(length and frequency), with video inputs assessing participant 
compliance with proper technique. The attendance times will be 
saved in the mobile applications backend data, and assessed by 
BMIC and the biostatistician for total practice time by individual 
and group participants.  
Primary; 
Acceptability 
12 
weeks 
Acceptability of using the mobile app to support symptom 
management for survivors will be evaluated using satisfaction 
rating scales, and system usability scale. At the end of each 
session a smiley face satisfaction survey will be used to capture 
the satisfaction of participants; at the end of 12 weeks, a System 
Usability Scale questionnaire will be administered. 
Primary; 
Feasibility 
12 
weeks 
Feasibility will be examined by evaluating intervention delivery 
factors (i.e., ease of use, barriers) and resource needs (i.e., staff 
time, session length, software or mobile connection challenges). 
Data on intervention delivery factors will be collected from 
participants at study termination (Week 12) using a structured 
focus interview. Resource needs will be evaluated over the 
course of the 12-week program . 

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Type 
Name 
Time 
Frame 
Brief Description 
Secondary; Behavioral 
Survey Measures 
Week 1 
and 
Week 
12 
Behavioral survey measures will be collected from all 
participants at study termination (Week 12) using established 
questionnaires ( perceived stress, depression scale, MD 
Anderson Symptom Inventory). 
Secondary; Focus Group 
Interview 
Week 
16 only 
Structured focus group interviews, to be completed at the end of 
the end of 12 week intervention, will assess participants' general 
perceptions of the intervention and technology. During these 
interviews, data will also be collected to identify 
recommendations for app modifications and improved 
adherence. 
Other; 
Exploratory 
salivary and 
fingernail 
biomarkers 
Week 1 
and 
Week 
12 
40 participants will provide 80 fingernail samples (Weeks 1 and 
12), and 160 saliva samples (Pre and Post YB/AC at Weeks 1 
and 12). Proteomic, multiplex, and ELISA will be used to 
measure changes in cytokines, tumor suppressors, and stress 
biomarkers. 
 
 
 
5.0 
Inclusion and Exclusion Criteria/ Study Population 
All Radiation Oncology staff at MUSC are cross trained in research referral to study staff for all potential 
participants, and research staff are closely connected to the clinic staff. Potential participants will be 
screened by the study radiation oncologist (PI) and study coordinator using oral questions and medical 
records about their diagnosis, radiation treatment and willingness to participate in the study.    
   
Inclusion criteria.  
1. Age 18 or older, willing to give informed consent  
3. Diagnosis of Stage 0-III breast cancer  
4. Completion of radiation therapy within last 6 months 
5. ECOG performance status of 0-4 during cancer treatment  
6. Orally expressed visual and auditory acuity adequate for filling out all study forms and participating in 
telephone interviews and internet-based group video applications  
7. Access to telephone, and internet-connected computer or mobile phone.  
 
Exclusion criteria.  
1. Subject is unwilling or unable to comply with any of the study procedures  
2. Orally expressed current dependence on alcohol or drugs  
 
Inclusion of Women and Minorities  
This study will include only women, as current breast cancer survivors are predominantly women. The 
inclusion of minorities in breast cancer survivorship is recognized as being of critical importance due to 
increased mortality and morbidity among African Americans. Based on our preliminary studies from 
Hope Lodge, and Survivors’ Fit Club, we will have minority representation as follows: 35-50% African 
American, 8-10% Hispanic, and 4-6% Asian American. Based on our past success in recruiting 
individuals from diverse racial and ethnic groups, we do not anticipate problems with hitting our target 
enrollment numbers from these groups and at rates proportionate to their representation in our catchment 
area. Existing Datasets or Resources. None to report.  

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Inclusion of Children and Individuals Across the Lifespan Women 18 years and above will be 
included in the study. There is a very low occurrence of breast cancer among women under 18, and thus 
no children will be recruited in the present study. 
 
6.0 
Number of Subjects 
A total of 40 breast cancer patients will be recruited for this study.  This pilot study will 
enroll a total of 40 study participants, 20 subjects per study arm. Given this sample size, 
we will be able to estimate differences between the groups within a margin of error of 
14.2% with 95% confidence level. 
7.0 
Setting 
The study will be centrally managed by PranaScience Institute, headed by Dr. Sundar Balasubramanian, 
and the subjects will be referred to the study by the sub-award PI Dr. Harper Professor, Dept. of Radiation 
Oncology at the Medical University of South Carolina (MUSC). PranaScience offices, located near the 
Medical University of South Carolina campus in downtown Charleston, SC.  
Mindfulness instructor Katharine Hendrix works with the PI on a number of research projects. For this 
study, she will act as a consultant to provide yogic breathing instruction to study participants at study 
initiation, and weekly support thereafter.  
Consent processes, yogic breathing instruction, app demos, collection of patient surveys and focus group 
interviews, as well as all data meetings, will take place at PranaScience office facilities in dedicated office 
and conference spaces, or completed remotely via telephone, video conferencing applications and 
electronic data collection instruments. The physician investigatorswill advise the study team on breast 
cancer diagnoses, radiation treatment, side effects, disease prognosis, ECOG performance status, and 
management of symptoms. Physician investigators will also help with recruiting and informing potential 
study participants about the research study. Dr. Sterba, Associate Professor, Department of Public Health 
Sciences, MUSC, will conduct focus group interviews along with the study coordinator at the 
PranaScience conference room and collate the data from the interviews.  The PI will have biweekly 
meetings with the research team including the research coordinators at SCTR, Dr. Balasubramanian and 
Dr. Hendrix through email or phone calls.  
 
8.0 
Recruitment Methods 
Recruitment: Charleston, SC, home of the PranaScience Institute and Medical University of South 
Carolina (MUSC), Hollings Cancer Center, along with the Roper Breast Care Center, is the site of a large 
number of cancer treatment outcome studies each year, including several studies on breast cancer. As 
such, all Radiation Oncology staff are cross trained in research referral to study staff for all potential 
participants, and research staff are closely connected to the clinic staff. Specifically, this study will use the 
following recruitment plan, which involves 6 potential entry paths to the project.  
 
Following IRB approval, 1) an information brochure advertising the study will be mailed to the growing 
MUSC roster of over 1,500 breast cancer survivors; 2) recruitment flyers will be placed in prominent 
locations in MUSC, the Roper Breast Care Center, Hope Lodge, MUSC Wellness Center and clinics 
within the Charleston metro catchment area; 3) the study will be posted on the MUSC “active research 
projects” web page, at SCresearch.org, and on ClinicalTrials.gov; 4) the study will be advertised via 
weekly newspaper research recruitment sections (MUSC) and on social media, particularly in facebook 
groups of cancer survivors and support groups; 5) patients may be referred to the study by the 
participating investigators/clinicians; 6) a series of advertisements will be run in relevant local 
newspapers if the first 5 strategies are ineffective. The PranaScience Institute, under Dr. 
Balasubramanian’s  direction, provides active breathing exercise classes to several target patient 
populations including breast cancer patients and survivors.. Potential participants will be screened by the 

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study coordinator and the PI, and the recruitment letter that contains the contact number of the study 
coordinator will be sent to the potential participants. Those that are interested will call the number for 
confirming their eligibility. The eligibility will be confirmed by oral answers provided by the participants 
over the telephone or their medical records reviewed by the PI and the coordinator. The coordinator will 
then schedule an appointment for the first visit (week 1) at the PranaScience office. At the first visit, the 
informed consent procedure will take place. The participants will then be randomized to condition by the 
study coordinator using the randomization protocol designed by the study statistician (Dr. Ramakrishnan).  
 
9.0 
Consent Process 
 
Eligible participants that are screened by the study coordinator and the PI will be contacted by the 
recruitment letter sent by the PI. Potential participants can contact the study coordinator directly from the 
details presented in the recruitment advertisements. Those that are eligible will be scheduled by the Study 
Coordinator for the first visit at which the written informed consent will be obtained from the participants. 
This visit will take place at the PranaScience facility at a time mutually agreed upon by the participant and 
the Study Coordinator, or completed remotely via telephone with the use of an electronic consent. In a 
private one-on-one setting the Study Coordinator will explain the study details including the goals of the 
study, number of participants, number of visits by each participant, required exercises to be done on the 
video chat using the mobile application, biological samples to be collected, focus group interviews, risks 
and benefits to the participant, and monetary compensation for participation. The participant can take their 
time to read the Informed Consent Form in entirety and ask questions to clarify any questions that they 
may have. Once the participant is satisfied with the details of the study information they will sign the 
Informed Consent Form. A copy of the signed Informed Consent Form will be given to the participant by 
the Study Coordinator.  After consent is obtained, participants will be randomized to YB or AC group and 
they will be progressing to the week 1 study visit procedures on a one-on-one basis with the study 
coordinator and the instructor. There is no waiting period between signing the consent and the baseline 
measurements.   
 
10.0 Study Design / Methods 
 
After consent is obtained, participants will be randomized by the study coordinator to YB or AC group 
and the study coordinator will provide the link to download the YB or AC app depending upon the group 
assignment. Any technical assistance in downloading the app will be provided by the study coordinator. 
For privacy and health reasons, the study coordinator will not touch the participant’s mobile device at any 
time. The coordinator will have a separate device for demonstrating the download procedures. At study 
initiation (Week one) at PranaScience location, participants will complete the baseline behavior 
assessment measures, medical history, demographics review, and will provide fingernail clippings. 
Baseline scores will be established for all measures. Participants who are unable or unwilling to complete 
the baseline visit in person may be able to complete the baseline visit remotely.  If the visit is conducted 
remotely, study staff will use telephone or video conference applications to meet with the participant and 
provide instructions for the visit. Participant surveys will be sent to the participant as electronic surveys to 
complete.  A sample collection kit will be sent to the participant prior to the visit with instructions on how 
to collect and ship samples. Participants will also take part in a one-on-one training session with the 
mindfulness instructor Dr. Katharine Hendrix to familiarize them with the app features and the proscribed 
AC or YB exercise. Passive drool whole saliva will be collected (2-5 mL) before and after the AC or YB 
exercise. For the remote sample collection, the saliva will be collected using FDA-approved filter paper 
discs shipped to the participants. Instructions will be provided to collect and ship the saliva back to the 
PI’s lab.   

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The mindfulness instructor will demonstrate how the App will work to facilitate the group sessions. For 
example, when a YB group participant opens the App and enters into the virtual meeting, the App will 
notify all the other participants from within the YB group that a participant from their group is available 
to practice together. This step will motivate other participants to join the meeting room. The participant 
can choose to practice alone or choose to allow more participants (2-7 participants allowed). The 
participants can also ‘lock’ the meeting space when all of them within the room decide to lock the room 
so they can start the practice without interruption. They can choose to keep it open so others can join. The 
App will have a timer to start the 10 minutes practice and will ring a bell at the end of 10 minutes. At the 
end of the practice, a smiley face satisfaction survey will appear for individual participants that they will 
be asked to submit by single click. The participants can stay in the room to chat or leave or continue with 
longer practice. The App will count the practice times as those in between the timer bells. The App will 
also capture information on how long and how frequent a participant accesses the App.  The similar 
procedure will happen for the AC participants where the YB exercise will be replaced with a mindfulness 
practice.  While on study, each participant will be engaging in group video AC or YB practice upon 
initiation based on the notification by the app or a group member. There will be 3-4 subgroups for each 
AC or YB group each containing 5-7 participants. If a participant does not access the app for more than 
24 hours during weekdays (Monday through Friday), then the App will send a reminder notification to 
motivate them to practice (For example, “Hello XXX, We hope you are doing well. We have not seen you 
practicing the mindfulness exercise yesterday. We understand you may be busy. We hope you can catch 
up with the practice when you get a chance. Have a good day!”). The motivational messages, reminders 
and any other text messages sent from the App to the participants will be appropriately tailored by the 
study biobehavioral co-investigator Dr. Sterba.   
 
Each YB session will open with a short question-answer to assess (a) what motivated the user to open 
app, (b) when was the previous large meal, and (c) which nostrils are open/blocked. Participants that 
answer that both nostrils are blocked will be recommended to try the exercise at a later time when they are 
able to breathe freely. Once the participant enters into the group meeting area everyone can see and hear 
the other participants. To protect privacy, the participants can use any privacy protection methods such as 
renaming, wearing eye masks, replacing their images with other images (for example, Avatars on zoom), 
and turning their video off. However, when the mindfulness instructor is present to assess the exercise 
compliance by participants on a random basis, then the video has to be turned on to make sure that the 
participant uses the right technique. These options will be explained to the participants during the 
introduction of the App by the study coordinator. The provider window will show YB instructional video 
or visual/audio cues chosen by the group. Additional support videos will be provided via an online link 
that can be accessed for reference by the users. All those in the group will practice the YB exercise for 10 
minutes. At end of session, a second Question and Answer (Q&A) session will assess (a) satisfaction 
using a facial expression scale, and (b) offer the option to set a reminder for the next practice.  
 
AC sessions will be identical in format to YB sessions except for following differences: (a) recorded 
session with instructor will guide the user though a mindful exercise. Namely, user group will be guided 
to close their eyes or to focus on the screen (same visual displays and music will be used for YB and AC 
modes). No instruction will be given related to breathing or breath control. While on study (Weeks 2-11), 
Dr. Hendrix will join the virtual group exercise sessions on a weekly basis to each group to encourage 
compliance with study protocol and collect data regarding barriers. The app will additionally employ 
motivational nudges and reminders throughout the study. 
  
At end of study visit on week 12, participants will complete post-study behavioral assessment measures 
and a system usability scale. Fingernail and saliva samples will be collected similar to baseline. As with 
the Baseline visit, this visit may be completed in-person at the PranaScience location, or remotely. After 
completing the study, participants will be asked to participate in a 60-minute, audio-taped focus group 

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interview at (N= 2 groups; one for each study arm [AC or YB]) that will assess their perceptions of the 
program and technology (i.e., ease of use, recommendations for app modifications and improved 
adherence). The focus group will be completed via video conference approximately 1-6 months after a 
participant completes the study.  
 
From the mobile App, data such as how many times the participant opened the mobile App, how long was 
each practice, and if the practice involved group or individual practice will be collected. No study data 
will be stored in participants' devices. All the data will be transmitted to secured cloud storage and the 
Medical University of South Carolina's Biomedical Information Center (BMIC) where it is stored 
securely. The participants will be able to access their personal data on the history of their practice. 
Subjects will be required to agree to Terms of Use or EULA or Privacy Policy document (to be provided 
to the IRB in the future) at the time of downloading the App. During the first clinical visit the research 
coordinator will provide the participants a link from where the participants will download the App. The 
App will work on iPhones, Androids, and on desktop/laptop computers. The app is not available on app 
stores. Once the study is completed, at the visit 2 (week 12) the participants will be asked to delete the 
App. They will no longer be able to access their data from BMIC. 
 
11.0 Specimen Collection and Banking (if applicable) 
Saliva samples and fingernail samples will be collected at the PranaScience location by the study 
coordinator from participants for protein and stress hormone analysis.  
Saliva: 
Saliva (about half a teaspoon) will be collected by passive drooling into a collection tube or by using filter 
paper discs at four time points as described below:  
Saliva Sample 1: Visit 1 on week 1. Before the study exercise. 0 minute 
Saliva Sample 2: Visit 1 on week 1. After the study exercise performed for 10 minutes.  
Saliva Sample 3: Visit 2 on week 12. Before the study exercise. 0 minute 
Saliva Sample 4: Visit 2 on week 12. After the study exercise performed for 10 minutes.  
Enough time will be given to participants to collect the saliva.  
Saliva samples will be sent to University of Houston Biomedical Engineering Eve Biotechnology 
(Calgary, Canada) for analysis of tumor suppressors and cytokines using multiplex methods. We 
additionally propose to analyze the salivary microbiome to further understand the stress response in 
patients before and after the intervention. For the salivary microbiome assay the samples will be sent to 
the University of Utah (The samples will be analyzed by researchers at the University of Utah in 
collaboration with University of Arkansas Medical Sciences Medical Center).    
 
Fingernails:  
Fingernails from the participants will be collected by self-grooming methods (participants cut their own 
fingernails using the clean nail clippers provided to them) at the following study visits. The fingernail will 
be used for proteomic analysis and cortisol measurement. At the time of study eligibility confirmation and 
scheduling the first visit, the participants are asked to leave the nail uncut for at least one week prior to the 
visits.  
Fingernail Sample 1: Visit 1 on week 1. Before the study exercise.  
Fingernail Sample 2: Visit 2 on week 12. Before the study exercise. 
Fingernail samples will be submitted to MUSC Proteomics facility for proteomic analysis, and to Eve 
Biotechnology for cortisol Cortisol estimation will be performed in the PI’s lab at MUSC.  
 
All the samples will be identified by the subject ID number, without any names or personal identifiers, 
and stored at -80oC freezer at the Radiation Oncology laboratory space (DD 329 where the PI has 
laboratory space). The samples will be shipped to the analytical labs on dry ice. The analysis data will be 
Commented [KEM1]: Insert new lab name 
Commented [KEM2]: Review this language to ensure it covers 
the analysis that you are wanting to do.  Please add additional 
description of analysis to be performed if the current language does 
not cover this.   
Commented [KEM3]: Insert new lab name 

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transmitted through secured web servers to the study PI and will be uploaded into REDCap for analysis 
by the biostatistician. Dr. Balasubramanian will oversee and coordinate the sample collection, shipment, 
analysis, and data collection. No genetic testing will be conducted using the samples. The samples will 
not be shared with any other investigators or any other purposes. 
Any remaining samples will be discarded after the study is completed.  
 
12.0 Data Management  
 
Statistical Considerations: 
The primary purpose of this study is to evaluate the feasibility of the group video Yogic Breathing app 
intervention. We will employ a parallel intervention model to compare the Yogic Breathing (YB) 
intervention to the control, an Attention Control (AC) intervention. After obtaining consent, participants 
will be randomly assigned to either group using a permuted block randomization approach; participants 
will be blinded to the study design as they will be assigned to one of the two mindful breathing exercises. 
The statistician will also be blinded to the study arms to reduce bias.  
This pilot study will enroll a total of 40 study participants, 20 subjects per study arm. Given this sample 
size, we will be able to estimate differences between the groups within a margin of error of 14.2% with 
95% confidence level. Specifically, with regards to the methods used to evaluate each outcome measure:  
1) Adherence (Primary Measure)  
Adherence will be measured using total practice times (length and frequency). This data will be collected 
throughout the 12week program on all practices recorded in the app. Compliance is ensured by random 
virtual group visits by the study mindfulness instructor, and compliance is inherently built in with the peer 
support model. Adequate adherence will be defined as completion of at least 10 practices a week (10-min 
each), and a total of 70% of all possible sessions (126 of 180 possible sessions). We will be able to 
estimate this percentage within a margin of error of 14.2% with 95% confidence level.  
2) Acceptability (Primary Measure)  
Acceptability of using the group video app to support symptom management for survivors will be 
evaluated using a satisfaction and system usability scale (SUS). This survey measure will be collected 
from all participants at study termination (Week 12). Adequate acceptability will be defined as an overall 
average SUS score above 68, which is well-established from a number of research studies to represent an 
“above average” rating of usability.  
3) Feasibility (Primary Measure)  
Feasibility will be examined by evaluating intervention delivery factors (i.e., ease of use, barriers) and 
resource needs (i.e., staff time, session length, software or mobile connection challenges). Data on 
intervention delivery factors will be collected from participants within one month of study termination 
(Week 12) using a structured focus interview until saturation. Focus group interviews will be evaluated 
using thematic analysis with N-Vivo software (NVivo Qualitative Software, by QSR International) to 
identify themes and intervention implications in interview transcriptions to inform future design changes 
with adherence to rigorous qualitative data analysis standards. This initial theme identification process 
will be followed by team meetings to finalize themes and implications for the intervention design. 
Resource needs will be evaluated over the course of the 12-week program and serve to inform design 
changes needed for large-scale implementation.  
4) Behavioral Survey Measures (Secondary Measure)  
Behavioral survey measures will be collected from all participants at study termination (Week 12) using 
established questionnaires and will help guide effect sizes and power calculations for the next larger-scale 
study (i.e., perceived stress, depression scale, anxiety scale, sleep quality measure, and MD Anderson 
Symptom Inventory [MDASI]). We will estimate the difference between the YB and AC groups for using 
a longitudinal mixed effects model. For MDASI, a 0.5 SD change is considered clinically significant. In 

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addition, we will estimate the within-subject intra-class correlation (using an AR(1) or CS structure) and 
variance. These assessments will guide effect sizes and power calculations for a Phase II pivotal study.  
5) Focus Group Interview (Secondary Measure)  
In addition to providing data on feasibility (see above), structured focus group interviews will assess the 
participants’ general perceptions of the intervention and technology. During these interviews, data will 
also be collected to identify recommendations for app modifications and improved adherence. Interview 
transcriptions will be evaluated using thematic analysis with N-Vivo software to identify themes and 
intervention implications to inform future design changes with adherence to rigorous qualitative data 
analysis standards. This initial theme identification process will be followed by team meetings to finalize 
themes and implications for the intervention design.  
6) Salivary and fingernails biomarkers (Exploratory Measures)  
Our prior research shows salivary biomarkers alter as a result of yogic breathing. However, they were not 
tested in cancer patients. Therefore, to identify potential target biomarkers in cancer population that would 
alter as a result of yogic breathing exercise in our future large scale studies we propose performing 
salivary (cytokines 71plex panel, tumor suppressor DMBT1), fingernails (cortisol, and differential 
proteomics) analysis. Regression methods will be used to identify significant predictors among the 
biomarkers. Stepwise selection methods will be used for this purpose. Also, data reduction methods will 
be considered to find factors among the biomarkers, which may provide more parsimonious predictions in 
the regression model. 
 
13.0 Provisions to Monitor the Data to Ensure the Safety of Subjects (if applicable) 
 
 
• Data Management and Quality Control Procedures: The primary responsibility for 
data management and quality control will remain with the PI. Study project 
coordinators are directed to promptly report any adverse effects related to the study 
intervention, assessment, recruitment protocols, or any other aspects of the study to the 
PI, who will report these adverse effects in writing within 24 hours to both the MUSC 
Institutional Review Board for the Protection of Human Subjects. Following each 
adverse event, a thorough investigation of the circumstances leading to the event, all 
probable causative factors, the current status of the event, the outcome of the event, and 
possible course of actions to avoid such events in future will be conducted by the PIs 
and Co-investigators. A written summary of findings will be submitted to the MUSC 
IRB. The collected data will be in the form of responses to structured interviews, self-
reports, and bio-behavioral assessment measures. Written forms of data will be 
encrypted with research numbers that are linked to participant identification number in 
a single Master List. This Master List is locked in the PI’s office in a secured research 
building. Only the PI will have keys to this file and only the project coordinator will 
have access to this room. The PI will review the collected data weekly to assure that all 
informed consent procedures are being followed, that all participant identifiers are 
removed from all collected questionnaires, and that all files are locked and secured. All 
the data entered into computer files will have only research numbers included, and no 
participant identifiers will be entered into digital format. The Master List of participant 
names and links to specific research numbers will be destroyed, and no link between 
identifiers and research numbers will remain upon completion of the study. Participant 
Safety Monitoring Procedures: All participants will be given the contact telephone 
number of the PI, and a 24-hour emergency contact/pager numbers. The participants 
will be strongly encouraged to call the PI or the emergency number if they experience 
any significant distress arising from study protocol. The PI will remain in contact with 

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any participants who reported a distress. In addition, the study staff will be clearly 
instructed to contact the PI if any of the participants report distress due to the protocol. 
The PIs will then contact these participants to assess the distress. In cases of extreme 
distress, the PI will make a decision regarding appropriate services or referrals. All 
adverse effects related to the interventions and assessment procedures or any aspect of 
the protocol will be documented in detail and reported within the stipulated time (24 
hours) to the MUSC IRB. Participant safety will be dealt with seriously at all steps of 
the protocol. All interview responses and data collected from the app will be uploaded 
into the REDCap system by the research coordinators. The MUSC Biomedical 
Informatics Center (BMIC) will consolidate the data, and biostatistician Dr. 
Ramakrishnan will analyze all data. The mobile application will be developed by 
PranaScience in collaboration with an information technology firm. 
14.0 Withdrawal of Subjects (if applicable) 
This is a pilot study determining the feasibility including intervention adherence. The participants will be 
informed that the participation is voluntary and can withdraw from the study at any time they would like 
by informing the study coordinator or any of the study team members. Withdrawing from this study will 
not affect the standard of care they receive as part of their survivorship.    
 
15.0 Risks to Subjects 
Potential Risks  
YB or AC exercises do not pose any potential physical and psychological risks to participants. The 
training provided at beginning of study will provide participants some familiarity with exercise before 
they engage with program independently, to improve confidence and decrease feelings of nervousness or 
inadequacy. There is in-built support by the other participants (peers) within each group session. All 
activities whether a person does the exercise alone or in company of others is counted as practice. Dr. 
Hendrix and Project Coordinators (provided by SCTR, see letter of support) will provide additional 
support to participants to ensure that the subjects feel at ease and comfortable during study. The study 
participants will not be contacted for another study.  
 
Some potential social risk to participants does exist, centered around threats to confidentiality and 
anonymity. However, by taking steps to maximizing anonymity and confidentiality we will greatly 
minimize such risks. These steps include removal of all personal identifiers (name, address) from 
collected data and replacing them with subject identification numbers. One Master List linking names 
with participant identification number will be secured in a locked facility and will be destroyed 
immediately upon completion of data collection. To improve privacy in the exercise sessions participants 
can rename themselves, use any makeovers (like eye masks) to modify identity, and use any Avatars to 
mask their identity. The App will not collect any audio or video recording of the sessions. 
 
If the participants experience any extreme physical or mental distress secondary to participating in this 
study, they will be encouraged to contact the PI or a Co-Investigator immediately. At the beginning of the 
initial interview, the participants will be provided these contact numbers and an additional 24-hour 
emergency contact number. If any of the study personnel notice any adverse effects in response to, or in 
potential response to any project intervention, assessment protocol, or study involvement, they will 
immediately notify the PI. The PI will then inform the MUSC IRB within 24 hours of the initial report. It 
is the PI’s responsibility to address all the concerns of the participants and to set up appropriate medical 
referral if necessary.  
 
16.0 Potential Benefits to Subjects or Others 

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Substantial evidence suggest that Yogic breathing contributes positively to overall health and wellbeing. 
Several studies indicate that both YB reduces stress and improves the quality of life in multiple patient 
groups including breast cancer patients and in otherwise healthy individuals. Our preliminary assessments 
suggest that YB leads to psychological improvements. Subjects of this study will accumulate new 
techniques to regulate breathing that they can practice daily at their will, leading in some cases to 
continuous practice that stand to provide long-term benefits. The new opportunity created through this 
app for social interaction with other survivors will help guide them in improved lifestyle choices and 
overall well-being.  
 
Importance of the Knowledge to be Gained  
YB is a non-invasive, non-pharmacologic, and inexpensive method. It is a time-tested intervention with 
documented benefits on physical and mental well-being. Additional scientific evidence is however needed 
to support the health claims of such holistic practices in order to reap their fullest preventive and 
therapeutic potential. Our study will provide initial support that a structured group video app-based YB 
intervention could be very useful to a) improve quality of life for survivors, and b) obtain initial data on 
feasibility and adherence to such an intervention. This is highly relevant for the continued wellbeing of 
individuals that are living with medical and psychological consequences of cancer treatment. In addition, 
these methods, once widely practiced, may help to prevent the onset and/or progression of future physical 
and mental illnesses. In summary, hundreds of thousands of Americans who have undergone cancer 
treatment and associated disease burden, psychological distress, mental disorders and compromised 
quality of life could be significantly helped by an effective, inexpensive YB adjunct therapy easily 
accessed via a mobile platform. 
 
17.0 Sharing of Results with Subjects 
The subjects who are interested in receiving copies of their data can get a copy of it at the end of the 
study. Their contact details and consent to contact them will be obtained at the time of informed consent 
process. No data belonging to other participants will be provided to any participant.   
 
 
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