A Randomized Controlled Trial of a Group-Based Therapeutic Yoga Intervention for Urinary Incontinence in Ambulatory Older Women
Phase: NA
Conditions: Stress Incontinence, Female, Stress Incontinence, Urinary, Stress Incontinence, Urge Incontinence, Urinary Incontinence, Stress, Urinary Stress Incontinence, Urgency Urinary
Sponsor: University of California, San Francisco

 
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A Randomized Controlled Trial of a Group-Based Therapeutic Yoga Intervention 
for Urinary Incontinence in Ambulatory Older Women 
 
NCT03672461 
 
Version Date: 02/27/2023 
 
IRB Approval Date: 03/10/2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Lessening Incontinence through Low-impact Activity 
(LILA) 
(a.k.a. A Randomized Controlled Trial of a Group-Based Therapeutic Yoga Intervention 
for Urinary Incontinence in Ambulatory Older Women) 
 
 
Principal investigator: 
 
Alison Huang, MD, MAS 
Associate Professor of Medicine, Urology, and Epidemiology and Biostatistics 
University of California San Francisco 
 
 
Supported by: 
 
The National Institute of Diabetes, Digestive, and Kidney Disorders 
Grant #1R01DK116712-01A1 
 

 
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Protocol Revision History 
 
Version Number: 1.0  
Version Date: 10/18/2018 
 
Version Number: 2.0  
Version Date: 11/16/2018 
Section 4.2: Clarified Exclusion Criteria 
Section 5.2: Added National Strength and Conditioning Association an approved society 
for certification  
Section 6.15: Replaced SPPB with Balance Testing and 30 second chair stand. 
Section 6.18: added Fluid Intake Questionnaire 
Section 6.25: Added 9-Week Phone Call description 
 
Version Number: 3.0  
Version Date: 01/24/2019 
Section 6.1.7a: Perineometer measurements 
 
Section 7.1: added Potential Risks of Perineometer measurement 
 
Version Number: 4.0  
Version Date: 02/25/2019 
Section 5.2: discovered the National Strength and Conditioning Association (NSCA) was 
not added within the text of the protocol, although this was listed above. 
 
Version Number: 5.0 
Version Date: 06/11/2019 
Sections: 6.1.8 Additional Screening and Covariate Measures and 6.2.7 Study 
Measurements Table: discovered that blood pressure and weight 
measurements were incorrectly indicated at week 6. Therefore, we are 
correcting the protocol to correctly reflect the approved informed consent 
document. 
 
Version Number: 6.0 
Version Date: 10/02/2019 
Section: 6.2.5 
Follow-up/Final Evaluations: We discovered a typo in the 
visit window for 36 weeks. The text should state “Within 273 days (39 
weeks)”, rather than “Within 252 days (39 weeks)”. Therefore, the protocol 
has been corrected to include the correct number of days for 39 weeks.  
 
Version Number: 7.0 
Version Date: 6/12/2020 
Sections 5.1 and 5.2 added the possibility of remote class instruction during COVID 
Pandemic  
Sections 6.16 and 6.17: During the COVID-19 pandemic, participants may decline 
measurements due to close proximity with study personnel.  
Section 9.6.2 Due to COVID 19 Pandemic, we may utilize subgroup analyses for to 
evaluate differences in remote instruction and in-person instruction. 

 
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Version Number 8.0 
Version Date: 7/14/2021 
Sections 3.0 and 9.2 have been updated to 250 participants randomized, with about 125 
participants per group, recognizing that baseline frequency of urinary 
incontinence may be closer to 22-23 rather than 25 episodes per week. 
Sections 6.25 has been updated to indicate that selected participants in the yoga arm 
may be invited to take part in qualitative interviews after the 12-Week Visit to 
discussed perceived barriers and facilitators to learning to practice yoga. 
 
Version Number 9.0 
Version Date: 02/27/2023 
Sections 3.0 and 9.2 have been updated to 240 participants randomized, with about 120 
participants per group, recognizing that baseline frequency of urinary 
incontinence may be closer to 23-24 rather than ~22-23 episodes per week. 
 
 

 
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TABLE OF CONTENTS 
PRÉCIS ........................................................................................................................................ 8 
1. 
STUDY OBJECTIVES ........................................................................................................... 9 
2.  BACKGROUND AND RATIONALE .................................................................................... 10 
2.1 Background on Condition ........................................................................................... 10 
2.2 Study Rationale .......................................................................................................... 10 
3.  STUDY DESIGN ................................................................................................................. 11 
4.  SELECTION AND ENROLLMENT OF PARTICIPANTS .................................................... 12 
4.1 Inclusion Criteria ......................................................................................................... 12 
4.2 Exclusion Criteria ....................................................................................................... 12 
4.3 Study Enrollment Procedures ..................................................................................... 13 
5.  STUDY INTERVENTIONS .................................................................................................. 14 
5.1 Yoga Program ............................................................................................................ 14 
5.2 Muscle Stretching/Strengthening (i.e., Physical Conditioning) Control Program ....... 16 
5.3 Concomitant Interventions .......................................................................................... 18 
5.3.1 
Required Interventions .................................................................................. 18 
5.3.2 
Prohibited or Discouraged Interventions ....................................................... 18 
5.4 Adherence Assessment ............................................................................................. 19 
6.  STUDY PROCEDURES ...................................................................................................... 20 
6.1 Study Measures ......................................................................................................... 20 
6.1.1  Urinary Incontinence ........................................................................................ 20 
6.1.2  Incontinence-Related Quality of Life ................................................................ 20 
6.1.3  Depression, Anxiety, and Perceived Stress ..................................................... 20 
6.1.4  Yoga/Physical Conditioning Self-efficacy and Competency ............................. 21 
6.1.5  Physical Function/Performance Measures ....................................................... 22 
6.1.6  Cardiac Autonomic Function Measures ........................................................... 22 
6.1.7  Pelvic Floor Muscle Strength ............................................................................ 23 
6.1.8  Additional Screening and Covariate Measures ................................................ 24 
6.2 Evaluations ................................................................................................................. 24 
6.2.1 
Screening Evaluations .................................................................................. 24 
6.2.2   Consenting Procedure ..................................................................................... 25 
6.2.3   Screening Procedures ..................................................................................... 25 
6.2.4 
Randomization and Blinding ......................................................................... 26 
6.2.5 
Follow-up/Final Evaluations .......................................................................... 28 
6.2.6 
Early Termination (also see section below) .................................................. 31 
6.2.7  Table of Measures and Procedures ................................................................. 32 
7. SAFETY ASSESSMENTS ...................................................................................................... 33 
7.1 Potential Risks and Protective Measures ................................................................... 33 
7.2 Methods and Timing of Safety Assessments ............................................................. 35 
7.3     Adverse Events and Serious Adverse Events ........................................................... 35 
7.3.1  AE/SAE Definitions ........................................................................................... 35 
7.3.2  AE/SAE Documentation ................................................................................... 35 
7.4 Reporting Procedures ................................................................................................ 36 
7.4.1   SAE Reporting ................................................................................................. 36 
7.4.2   Non-Serious AE Reporting .............................................................................. 36 
7.5 Follow-up for AEs/SAEs ............................................................................................. 37 
7.6 Independent Safety Monitoring .................................................................................. 37 
8.   INTERVENTION DISCONTINUATION ................................................................................ 38 
9. STATISTICAL CONSIDERATIONS ....................................................................................... 38 

 
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9.1 General Design Issues ............................................................................................... 38 
9.2 Sample Size ............................................................................................................... 39 
9.3       Randomization and Blinding ................................................................................... 39 
9.4     Interim Analyses and Stopping Guidelines ............................................................... 40 
9.5 Outcomes ................................................................................................................... 40 
9.5.1 
Primary Efficacy Outcome ............................................................................. 40 
9.5.2 
Secondary Efficacy Outcomes ...................................................................... 40 
9.6 Data Analyses ............................................................................................................ 41 
9.6.1    Analyses to address main objectives ............................................................. 41 
9.6.2    Other analytic issues ...................................................................................... 43 
10. DATA COLLECTION AND QUALITY ASSURANCE ............................................................ 44 
10.1 Data Collection Forms ................................................................................................ 44 
10.2 Data Management ...................................................................................................... 45 
10.3 Quality Assurance ...................................................................................................... 45 
10.3.1 Staff Training ................................................................................................. 45 
10.3.2 Data Quality Assessment .............................................................................. 46 
10.3.3 Protocol Deviations ....................................................................................... 46 
10.3.4 External Monitoring ....................................................................................... 46 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY .............................................................. 47 
11.1 Institutional Review Board (IRB) Review .................................................................... 47 
11.2 Informed Consent Forms ............................................................................................ 47 
11.3 Participant Confidentiality ........................................................................................... 47 
11.4 Study Discontinuation ................................................................................................. 47 
12.  ETHICAL CONSIDERATIONS ............................................................................................ 47 
13.  STEERING/PUBLICATIONS COMMITTEE ........................................................................ 47 
14.  PUBLICATION OF RESEARCH FINDINGS ....................................................................... 48 
15. REFERENCES ..................................................................................................................... 48 
 

 
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STUDY TEAM ROSTER  
Investigators 
 
Alison Huang, MD, MAS 
1545 Divisadero Street, Suite 322 
San Francisco, CA 94115 
E-mail: ahuang@medicine.ucsf.edu 
Tel: 415-514-8697   F: 415-514-8666 
Leslee Subak, MD 
300 Pasteur Drive, HG332, Office #G-303A 
Stanford, CA  94305-5317 
E-mail: lsubak@stanford.edu 
Tel: 650-723-5533 F: 650-723-7737 
Margaret Chesney, PhD 
1545 Divisadero Street, Suite 508 
San Francisco, CA 94115 
Email: chesneym@ocim.ucsf.edu 
Tel: 415-353-7719   F: 415-353-7711 
Wendy Mendes, PhD 
3333 California Street 
San Francisco, CA 94118 
Email: Wendy.Mendes@ucsf.edu 
Tel: 415-476-7409 
Eric Vittinghoff, PhD 
550 16th Street, 3rd Floor 
San Francisco, CA 94158 
Email: Eric.Vittinghoff@ucsf.edu 
Tel: 415-514-8025 
Project Directors 
 
Ann Chang 
550 16th Street, 6th Floor 
San Francisco, CA 94158 
Email: Ann.Chang@ucsf.edu  
Tel: 415-353-9782   F: 415-476-5367 
Lisa Abinanti 
550 16th Street, 6th Floor 
San Francisco, CA 94158 
Email: Lisa.Abinanti@ucsf.edu  
Tel: 415-353-9978   F: 415-476-5367 
Data Management and Statistical Analysts  
 
Michael Schembri 
550 16th Street, 6th Floor 
San Francisco, CA 94158 
Email: michael.schembri@ucsf.edu  
Tel: 415-353-7161  F: 415-476-5367 
Data and Safety Monitor 
 
Andrew Avins, MD, MPH 
Kaiser Permanente Division of Research  
2000 Broadway  
Oakland, CA 94612 
Email: andy.l.avins@kp.org  
Tel: (510) 891-3557 (phone)  

 
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PRÉCIS  
 
Study Title  
Lessening Incontinence through Low-impact Activity (LILA), a.k.a. A Randomized 
Controlled Trial of a Group-Based Therapeutic Yoga Intervention for Urinary 
Incontinence in Ambulatory Older Women 
 
Objectives  
To evaluate the efficacy of a group-based yoga intervention for urinary incontinence 
in ambulatory middle-aged and older women and explore potential mediators of 
intervention effects in this population. 
Study Design  
Randomized, multicenter, parallel-group trial of a 12-week yoga intervention versus 
non-specific muscle stretching/strengthening control intervention for ambulatory 
women aged 45 years and older with urinary incontinence.  
Sample Size and Population  
Two hundred fifty women aged 45 years and older who document stress-, urgency-, 
or mixed-type incontinence occurring at least once per day, are not participating in 
other organized yoga or muscle stretching/strengthening activities, are temporarily 
willing to forgo other established clinical treatments for incontinence, and meet 
minimum mobility and other clinical eligibility criteria, recruited from multiple locations 
in northern California.   
Interventions and Duration 
Participants will be randomized in a 1:1 ratio to participate in either a 12-week yoga 
program (N~120) or a time-equivalent non-specific muscle stretching/strengthening 
control program (N~120).  Women randomized to the yoga program will take part in 
twice weekly group yoga classes focusing on Iyengar/alignment-based yoga 
techniques and practice yoga at home for at least one hour per week for 12 weeks.  
Women randomized to the control program will take part in twice weekly group 
classes focusing on non-specific muscle stretching/strengthening exercises and 
practice these exercises at least one hour per week at home for 12 weeks.   
Study Outcomes 
The primary outcome is change in the frequency of any urinary incontinence 
episodes between baseline and 12 weeks, measured using validated voiding diaries. 
Secondary outcomes include changes in the frequency of stress-type, urgency-type, 
daytime, and nighttime incontinence episodes (also measured by voiding diaries), as 
well as changes in incontinence-related functioning or quality of life (measured by 
validated questionnaires), between baseline and 12 weeks. Additional secondary 
outcomes include persistence of changes in incontinence frequency and condition-
specific quality of life 12 and 24 weeks after the end of the intervention programs. 
 
 

 
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1. STUDY OBJECTIVES 
 
Objective 1: To determine the efficacy of a group-based yoga intervention in reducing the 
frequency of urinary incontinence in ambulatory midlife and older women.  
Hypothesis 1A: Ambulatory incontinent women randomized to the yoga intervention will 
demonstrate at least a 20% greater decrease in total incontinence frequency (measured by 
validated voiding diaries) over 12 weeks, compared to women randomized to the control 
intervention.  
Hypothesis 1B: If improvements in total incontinence frequency are observed at 12 weeks, 
these improvements will be sustained 12 and 24 weeks after the end of the intervention 
programs. 
Objective 2: To determine the efficacy of a group-based yoga intervention in reducing the 
frequency of type- and context-specific urinary incontinence in ambulatory middle-aged and 
older women.  
Hypothesis 2A: Ambulatory incontinent women randomized to the yoga intervention will 
report decreases in the frequency of stress-type, urgency-type, daytime, and nighttime 
incontinence (also measured by voiding diaries) over 12 weeks, compared to women 
randomized to the control intervention.  
Hypothesis 2B: If improvements in stress-type, urgency-type, daytime, and nightime 
incontinence frequency are observed at 12 weeks, these improvements will be sustained 12 
and 24 weeks after the end of the intervention programs. 
Objective 3: To determine the efficacy of the yoga intervention in improving incontinence-
related functioning and quality-of-life.  
Hypothesis 3A: Ambulatory incontinent women randomized to the yoga intervention will 
report greater improvements in condition-specific functioning and quality of life (assessed by 
validated questionnaires) over 12 weeks, compared to women randomized to the control 
intervention.  
Hypothesis 3B: Compared to women randomized to the control intervention, we hypothesize 
that women randomized to the yoga intervention will report sustained improvements in 
condition-specific quality of life 12 and 24 weeks after the end of the intervention programs. 
Objective 4:  To explore whether the yoga intervention is associated with improvements in 
1) pelvic floor muscle strength, 2) peripheral autonomic function, and/or 3) lower extremity 
physical function, and assess whether improvements in these factors may mediate 
improvement in incontinence.  
Hypothesis 4A: Among ambulatory incontinent women enrolled in this trial, the yoga 
intervention will be associated with improvements in a) pelvic floor muscle strength 
(assessed by pelvic exam), b) cardiac autonomic function (assessed by heart rate variability 
and impedance cardiography), and c) lower extremity physical function (assessed by 
physical performance assessment) over 12 weeks. 
Hypothesis 4B: Among ambulatory incontinent women enrolled in this trial, changes in 
incontinence frequency over 12 weeks will be partly mediated by changes in a) pelvic floor 
muscle strength, b) cardiac autonomic function, and c) lower extremity physical function. 

 
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2.  BACKGROUND AND RATIONALE 
2.1 Background on Condition 
Approximately one in four midlife and older women suffers from urinary incontinence, a 
condition associated with depression, social isolation, functional decline, falls and 
fractures, and admission to long-term care facilities.1-8  In economic analyses, the 
annual estimated direct costs of incontinence among U.S. women exceed $20 billion, 
greater than that of breast, ovarian, cervical, and uterine cancers combined.9 
Current first-line treatment for incontinence includes behavioral management 
strategies such as bladder re-training and pelvic floor exercises designed to increase 
bladder capacity, strengthen the pelvic floor muscles supporting the bladder, and 
suppress involuntary bladder contractions. Unfortunately, many patients who attempt 
to practice these techniques after routine teaching by general practitioners are not able 
to do so effectively.10-13  Although the efficacy of these techniques can be improved by 
one-on-one training and biofeedback with pelvic physical therapists or other 
specialized medical practitioners, this type of intensive pelvic floor rehabilitation 
therapy is costly, and access to trained pelvic physical therapists is limited.14,15   
Second-line treatment for urgency-type incontinence (i.e., urine leakage caused by 
sudden or strong urges to urinate) consists primarily of anticholinergic drugs that are 
modestly effective in reducing incontinence, but have multiple side effects such as dry 
mouth, stomach upset, constipation, and even cognitive impairment.  As a result, over 
half of patients who initiate anticholinergic therapy for urinary symptoms like 
incontinence discontinue it within a year.16-18  For stress-type incontinence (i.e., urine 
leakage with activities that increase abdominal pressure), surgery and other invasive 
procedures can be effective, but are poorly tolerated by many women, particularly 
older or frailer women who are at greatest risk of developing frequent incontinence.19  
As a result, there is a need for alternate treatment strategies that that are not only 
effective, but also more accessible and better tolerated. 
2.2 Study Rationale 
Yoga is a set of complementary physical and mental practices with the potential to 
improve urinary incontinence through multiple mechanisms, while also avoiding many 
of the shortcomings of existing clinical therapies. When taught in a way that 
emphasizes mindful awareness of specific bodily structures, yoga can be used to help 
women control and strengthen their pelvic floor muscles through a combination of 
group instruction and home practice. As a result, a group-based yoga program that 
incorporates practice of specific yoga postures to promote awareness and 
engagement of the pelvic floor may provide a more accessible alternative to traditional, 
one-on-one pelvic floor rehabilitation therapy.   
Yogic breathing and relaxation techniques also have the potential to improve 
peripheral autonomic dysfunction as another potential contributor to incontinence. Prior 
physiologic studies have demonstrated that many women with urgency-type 
incontinence have to have abnormalities in sympathetic and parasympathetic 
autonomic function.20-25  Yoga interventions that involve regular practice of yogic 
breathing have the potential to improve resting autonomic function as well as stress-
related autonomic reactivity,26-29 which could in turn lead to improved bladder control. 
Regular practice of yoga postures can also improve physical deconditioning as another 

 
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potential contributor to incontinence risk.5,30-33 Among frail older women, decreased 
physical conditioning and mobility can compromise women’s ability to get to the 
bathroom when they experience urges to urinate. Poor physical conditioning is also 
associated with increased abdominal obesity, which has been shown to contribute to 
both stress- and urgency-type incontinence symptoms. Several small studies have 
explored the benefits of physical exercise programs for preventing or managing 
incontinence in older women34,35; unlike yoga, however, these non-specific exercise 
programs did not have the added benefit of engaging the pelvic floor or directly 
improving autonomic balance in incontinent women. 
To examine the feasibility of using yoga to treat incontinence in middle-aged and older 
women, our research team previously developed a group-based, Iyengar-style yoga 
program consisting of twice weekly classes and once weekly home practice sessions. 
We subsequently pilot-tested and refined that program through an initial pilot 
randomized trial involving 19 women and a follow-up feasibility trial involving 56 
women. We will now conduct a rigorous multicenter randomized trial to determine 
whether the refined group-based yoga intervention is effective in decreasing the 
frequency and impact of urinary incontinence in middle-aged and older women and 
explore potential mediators of intervention effects in this population.  
3.  STUDY DESIGN 
This is a randomized, multicenter, parallel-group trial to determine whether a 12-week 
group-based yoga intervention is effective in decreasing the frequency and impact of urinary 
incontinence in middle-aged and older women. Women aged 45 years and older who 
document at least daily episodes of stress-, urgency-, or mixed-type incontinence on a 
screening voiding diary, are not using other clinical treatments for incontinence, and meet 
minimum physical mobility requirements and other eligibility criteria will be recruited from 
multiple locations in northern California by coordinators affiliated with the University of 
California San Francisco or Stanford University.  Eligible women will be randomized in a 1:1 
ratio to participate in either a 12-week yoga program (N~120) or a time-equivalent, non-
specific muscle stretching and strengthening control program (N~120).  
Women randomized to the yoga program will take part in twice weekly group yoga classes 
involving an expected 8 to 12 other women as well as practice study-specific yoga 
techniques at home for at least one hour per week for a total of 12 weeks.  Women 
randomized to the muscle stretching and strengthening (a.k.a physical conditioning) control 
group will take part in twice weekly group physical conditioning classes and practice 
physical conditioning exercises at least one hour per week at home for 12 weeks.  During 
the 12- and 24-week post-intervention follow-up period, participants will also be encouraged 
to continue practicing yoga or stretching/strengthening exercises for at least two hours per 
week. 
To address objective 1, we will use validated voiding diaries to examine changes in 
frequency of total incontinence during the 12-week intervention, as well as explore 
persistence of effects on incontinence frequency after the end of the intervention programs. 
To address objective 2, we will further examine changes in frequency of different clinical 
types of incontinence as well as daytime and nighttime incontinence during the 12-week 
intervention, as well as the post-intervention follow-up periods. To address objective 3, we 
will analyze data from validated questionnaires in order to examine changes in incontinence-
related functioning and quality of life over these same time periods. To address objective 4, 
we will assess changes in pelvic floor strength assessed during pelvic exam, autonomic 

 
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function assessed by heart rate variability and impedance cardiography measures, and 
physical function assessed by questionnaire as well as physical performance testing.  
This study design is designed to provide rigorous evidence to evaluate the efficacy of the 
yoga intervention for treatment of incontinence in women, as well as exploring multiple 
potential mediators of improvement in incontinence and incontinence-related quality of life. 
4.  SELECTION AND ENROLLMENT OF PARTICIPANTS  
Eligibility criteria have designed to identify a study population that is generalizable to most 
ambulatory middle-aged and older women with incontinence who do not have complicated 
urologic histories and also do not have a major contraindication to practicing yoga.   
4.1 
Inclusion Criteria 
Candidates must meet all of the following criteria to participate in the study: 
• 
Women aged 45 years or older who report urinary incontinence starting at least 3 
months prior to screening 
• 
Self-report at least 3 urinary incontinence episodes on a screening 3-day voiding 
diary (i.e., an average of at least one episode per day) 
• 
Self-report urgency-predominant incontinence (i.e., at least half of incontinence 
episodes being urgency-type), stress-predominant incontinence (i.e., at least half 
of episodes being stress-type), or mixed-type incontinence (i.e., an equal number 
of stress- and urgency-type episodes) on the screening voiding diary 
• 
Willing to refrain from initiating medical treatments that may affect their 
incontinence or voiding pattern during the study intervention period 
4.2 
Exclusion Criteria 
Candidates meeting any of the following criteria at baseline will be excluded from 
participation: 
• 
Participation in at least weekly formal or organized yoga classes or instruction 
within the past 3 months; or any prior yoga therapy directed specifically at 
improving urinary incontinence or pelvic floor dysfunction 
• 
Participation in at least weekly organized physical conditioning classes or 
instruction in the past 3 months (i.e., classes involving muscle stretching and 
strengthening exercises, not including aerobic classes that do not emphasize 
muscle stretching or strengthening). 
• 
Currently pregnant (by self-report or screening urine pregnancy test), gave birth 
within the past 6 months, or planning pregnancy during the study period 
(approximately 9 months) 
• 
Current urinary tract infection (screening dipstick urinalysis with leukocyte 
estrace, nitrites or blood) or a history or 3 or more urinary tract infections in the 
preceding year 
• 
Report history of neurologic conditions such as stroke, multiple sclerosis, spinal 
cord injury, or Parkinson’s disease, or a lumbosacral spine condition associated 
with neurological symptoms 
• 
Unable to walk up a flight of stairs or at least 2 blocks on level ground without 
assistance (i.e., functional capacity < 4 METs) 
• 
Unable to get up from a supine to a standing position in 10 seconds or less and 
without assistance 

 
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• 
Morbid obesity defined by a measured body mass index of >40 kg/m2 at the 
screening evaluation. 
• 
Report any history of prior anti-incontinence or urethral surgery (not including 
urethral dilation), pelvic cancer, or pelvic irradiation for any reason 
• 
Report use of bladder botox, electrostimulation, bladder training, or pelvic floor 
exercise training (with certified practitioners) in the past 3 months 
• 
Report other surgery to the pelvis (hysterectomy, oophorectomy, vaginal surgery, 
bladder surgery, colon surgery) within the past 3 months 
• 
Report use of medications with the potential to affect incontinence (anticholinergic 
bladder medications, tricyclic antidepressants, mirabegron, loop diuretics) within 
the past month 
• 
Report starting stopping, or changing the dose of a medication with the potential 
to affect depression or anxiety symptoms (i.e., selective serotonin reuptake 
inhibitors, anxiolytics/sedatives, antipsychotics) within the past 1 month, or plans 
to start, stop, or change to dose of such a medication during the study 
intervention period 
• 
Report use of medical devices (i.e. pessary) for incontinence within the previous 
month (participants may stop use of device and re-present for study) 
• 
Report history of interstitial cystitis, fistula or hole in bladder or rectum, or birth 
defect leading to urine leakage 
• 
Report symptomatic pelvic organ prolapse (assessed using a standardized 
question, “Have your pelvic organs (uterus, bladder, or rectum) been dropping out 
of your vagina causing a feeling of bulging, pressure, or protrusion or a sensation 
like your “insides are coming out”?”) 
• 
Report history of vulvodynia, chronic pelvic pain, or pain when practicing pelvic 
floor exercises  
• 
Report conditions that, in the judgment of the investigators, render potential 
participants unlikely to follow the protocol, including plans to move, substance 
abuse, significant psychiatric problems, or dementia 
• 
Participation in another research study that involves investigational drugs or 
devices that could potentially confound the results of this study  
• 
Unable to understand study procedures, complete study interviews, or and 
provide informed consent in English 
4.3 
Study Enrollment Procedures  
Recruitment:  Participants will be recruited from multiple locations in northern 
California using a multi-component approach that has been employed successfully in 
past clinical trials led by the investigators. This includes community-based media 
efforts (newspaper and radio advertisements, mass community mailings, notices 
posted in community and senior centers), recruitment from a database of women 
who have given permission to be contacted for women’s health research studies 
based at the University of California San Francisco (UCSF) or Stanford University, 
recruitment of current and/or former female patients at UCSF or Stanford University 
identified through searches of electronic clinical databases, and posting or display of 
recruitment fliers in clinician offices (such as general internal medicine, geriatrics, 
gynecology, or alternative medicine).  Recruitment will be organized in waves to 
assemble successive cohorts of women who are confirmed to meet all eligibility 
criteria and who are available to attend upcoming group yoga or muscle 
stretching/strengthening classes.  

 
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Screening: Preliminary eligibility will be determined by research coordinators through 
a Screening Telephone Interview followed by an in-person Screening Clinic Visit.  
During the Screening Telephone Interview, coordinators will follow a standardized 
screening interview script to assess preliminary eligibility related to age, gender, 
incontinence history, and exclusionary conditions and medications, as well as 
document reasons for ineligibility on the screening interview form. Candidates who 
appear preliminarily eligible at the end of the telephone interview will be scheduled to 
attend an in-person Screening Clinic Visit. After providing written informed consent at 
this visit, women will undergo more detailed assessment of incontinence symptoms, 
use of clinical incontinence therapies, exclusionary medical conditions, exclusionary 
medications, urine dipstick and pregnancy testing (for women of childbearing 
potential), and brief physical mobility assessment, with reasons for eligibility or 
ineligibility documented on the screening clinic intake form.   
At the end of the Screening Clinic Visit, women who appear eligible will be given a 
blank voiding diary and instructions for completing it at home over a 3-day period and 
returning it to study staff at a Baseline Clinic Visit. Those who are confirmed to have 
stress-predominant, urgency-predominant, or mixed urgency-stress incontinence 
occurring at least 3 times over the 3-day diary period and meet all other 
inclusion/exclusion criteria at the Baseline Clinic Visit will be considered eligible for 
randomization to one of the two intervention groups. 
Randomization: During each recruitment/randomization wave, eligible women will be 
randomized in a 1:1 ratio to one of the two intervention groups. Randomization will 
be stratified by clinical type of incontinence (i.e., stress, urgency, or mixed), to 
ensure adequacy of randomization within these three types. Randomization will be 
implemented by computer algorithm using randomly permuted blocks of sizes 2 and 
4, with proof of eligibility required before assignment. To avoid manipulation, 
standard allocation concealment procedures will be followed (see subsequent 
section on Randomization for more detail).   
To avoid excessive lag time between randomization and the start of the therapeutic 
yoga or stretching/strengthening control programs, randomization will take place no 
earlier than two weeks before the intervention program orientation sessions. For 
candidates whose Baseline Clinic Visit falls within this two-week window, 
randomization will take place directly at the Baseline Clinic Visit. For candidates who 
complete their Baseline Clinic Visit more than two weeks before the start of the yoga 
or control intervention programs, a Randomization Telephone Call will be scheduled 
to complete randomization within the two-week window. 
5.  STUDY INTERVENTIONS  
5.1 
Yoga Program  
Overview and rationale: The 12-week yoga program will provide instruction and 
practice in a variety of yoga postures and techniques that have been selected for 
their potential to improve bladder control as well as their safety and feasibility for the 
target population. The study yoga program will be based primarily on Iyengar yoga, a 
form of Hatha yoga that is known for its potential therapeutic applications, has been 
employed successfully in other studies of yoga for different indications,36-44 and 
differs from other Hatha yoga styles (power yoga, bikram yoga) in multiple ways that 
are likely to maximize both efficacy and safety for this study. Important features of 

 
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Iyengar/alignment-based yoga include: 1) emphasis on precise anatomical and 
postural alignment during practice of postures; 2) incorporation of props to minimize 
risk of injury and accommodate those with lower strength or flexibility; 3) emphasis 
on mindful awareness during practice of postures rather than rapid cycling through 
postures.  
The study yoga program, which was pre-tested and refined in the investigators’ prior 
pilot studies, is designed to maximize women’s awareness of and control over the 
pelvic floor and improve underlying autonomic balance and physical conditioning, 
while still being feasible for ambulatory women across a wide range of ages, as well 
as grounded in techniques common to Iyengar yoga at large.  
Content and postures: The yoga program will focus on a core set of 16 postures that 
are widely used in yoga practice and can be safely adapted for ambulatory women 
across a range of ages, including those with mildly or moderately decreased 
flexibility or mobility. These include both active postures engaging the pelvic floor 
and more passive postures promoting relaxation: Baddha Konasana (bounded angle 
pose), Malasana (squat pose), Bharadvajasana (seated twist pose), Supta Baddha 
Konasana (reclined cobbler’s pose), Parsvottasana (intense side stretch pose), 
Salabhasana (locust pose), Savasana (corpse pose), Salamba Set Bandhasana 
(supported bridge pose), Parsvokonasana (side angle pose), Utkatasana (chair 
pose), Trikonasana (triangle pose), Vajrasana (thunderbolt), Virabhadrasana 2 
(warrior 2 pose), Tadasana (mountain pose), Supta Padagushthasana (reclining big 
toe pose), and Viparita Karani Variation (legs up the wall pose). 
Staff qualifications and training: Each yoga class series will be led by a primary 
instructor who must: 1) have at least 2 years of experience teaching yoga in the 
community; 2) review a detailed, study-specific written instructor manual describing 
all of the postures and yoga techniques to be used in the study program; 3) complete 
at least 2 hours of in-person training in study-specific yoga techniques with one of 
the study yoga expert consultants; 4) complete additional study-specific training in 
clinical trial procedures, documentation of participant attendance, review of home 
practice logs, and recording of yoga postures practiced during group classes on 
appropriate study forms; 5) carry and submit proof of personal liability insurance 
(minimum of $2 million coverage); and 6) confirm his or her willingness to adhere to 
the study intervention procedures. For each class series, a back-up instructor will 
also be identified who can teach a class in the event that the primary instructor is ill 
or is unable to teach due to an emergency. 
Orientation and classes:  Prior to group instruction, participants in each class series 
will attend a 90-minute group orientation led by the appointed class instructor. This 
will include an overview of the general principles of Iyengar/alignment yoga, an 
orientation to the structures of the pelvis, spine, and lower extremity, and an 
introduction to the postures to be practiced and the props to be used in the study. 
After the orientation, women will attend 90-minute group classes twice weekly for 12 
weeks, led by the same instructor. For classes with 10 or more students, the 
instructor may be supported by an assistant who will help to provide personalized 
attention to students. During group classes with no more than 15 participants, the 
instructor will guide women in practicing yoga postures, calling attention to ways in 
which postures can improve pelvic floor function and adapt postures to 
accommodate physical limitations. Women will also be taught to avoid habits that 
may worsen incontinence during practice, such as squeezing of abdominal rather 
than pelvic muscles. Following a study-specific guide, instructors will gradually 

 
16 of 54 
 
 
 
introduce postures as classes progress, with the goal of making participants 
comfortable with all core postures by the end of 6 weeks and fully confident in 
performing postures by 12 weeks. During the COVID-19 pandemic, class instruction 
may be converted to remote platforms (i.e., may take the form of interactive on-line 
video-based classes rather than in-person classes). 
Home practice: In addition to attending group classes, participants will be asked to 
practice yoga at home at least one additional hour per week and will be given a diary 
to keep track of the dates and times of practice.  Women will also be given a written 
manual, pre-tested in the investigators’ pilot studies, that includes pictures and 
descriptions of each yoga posture to guide them in home practice. Each participant 
will be given a limited set of yoga props (a mat, belt, and 2 blocks) for home practice.  
Women will be encouraged to practice with other members of their classes, but will 
be discouraged from practicing with individuals who are not in their class and from 
taking part in non-study yoga activities that might dilute study techniques.  
Quality and safety: The study program will incorporate multiple modifications to help 
women across the age range to perform postures in ways that minimize risk of 
muscle strain or injury. Participant manuals will include specific instructions on 
adapting each posture and/or using props to accommodate problems with mobility, 
flexibility, or balance. To promote quality and safety, the instructors leading classes 
will be required to have at least 2 years of experience teaching yoga and have 
completed dedicated, study-specific training with the study’s expert consultants. 
Following procedures established in the pilot study, a consultant will visit at least one 
class in each series to ensure that postures are being taught according to protocol, 
evaluate students’ success in learning yoga, and ensure fidelity across instructors.  
Twice monthly conference calls will be conducted to help instructors trouble-shoot 
issues that arise in instruction. 
Post-intervention program continuation: After the end of the main 12-week 
intervention period, participants will be encouraged to continue to practice yoga at 
least two hours per week at home, although group intervention classes will no longer 
be offered through the study.  
5.2 
Muscle Stretching/Strengthening (i.e., Physical Conditioning) Control Program  
Overview and rationale: This trial will include a 12-week non-specific muscle 
stretching/strengthening program that will provide a rigorous time-and-attention 
control for the yoga program, but has been designed to avoid engaging the pelvic 
floor or promoting mindful relaxation. To minimize differential expectations of 
treatment success, women will be told that they are enrolling in a study of two 
different types of low-impact physical activity-based interventions (yoga versus 
physical conditioning) to enhance management of incontinence. Control group 
exercises have been adapted from exercises used in prior studies conducted by the 
investigators, such as the PRYSMS trial of restorative yoga vs. stretching for 
metabolic syndrome (designed by Sarah Pawlowsky, DPT, consultant on this 
proposal), and pilot-tested in the investigators’ prior pilot study of yoga versus 
physical conditioning for women with incontinence.  Similar to postures in the yoga 
program, the exercises in the stretching/strengthening program have been selected 
for their potential to be performed safely by women across a range of ages and 
flexibility levels. 
Content and exercises:  After a brief education about sitting and standing posture, 

 
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the control intervention program will focus on a core set of muscle stretching and 
strengthening exercises that will be performed sitting in a chair: levator scapulae, 
upper trapezius, scalenes, shoulder horizontal adduction, triceps, pectoral stretch 
with hands behind head, wrist flexors and extensors, trunk flexion, trunk extension, 
trunk side-bend, trunk rotation, and hamstring stretches.  Additional chair exercises 
will incorporate a stretching strap: pectoral stretch with strap, gastrocnemius stretch 
with strap, and hand behind back with strap.  A few stretches will be performed on an 
exercise mat on the floor: supine single knee to chest, supine hamstrings stretch with 
strap, quadriceps stretch with strap, supine shoulder flexion with stretch strap, and 
seated adductor stretch. Several exercises will be performed in the standing position: 
gastrocnemius, soleus, shoulder flexion, and shoulder abduction stretches. 
Staff qualifications and training: Each stretching/strengthening class series will be led 
by a primary instructor who: 1) is either certified as a personal trainer through the 
National Academy of Sports Medicine, National Strength and Conditioning 
Association, or the American College of Sports Medicine, or National Strength and 
Conditioning Association (NSCA), or licensed as a physical therapist by the Physical 
Therapy Board of California; 2) has at least 2 years of experience working as a 
physical therapist or physical trainer in either individual or group settings; 3) will have 
reviewed a detailed, study-specific training manual describing all of the 
stretching/strengthening exercises to be used in the study program; 4) will have 
completed at least 2 hours of in-person training in study-specific techniques with 
study expert consultant; 5) will have completed additional study-specific training in 
clinical trial procedures, documentation of participant attendance, review of home 
practice logs (for adherence), and recording of exercises performed during group 
classes on appropriate study forms; 6) carries and submits proof of personal liability 
insurance (minimum of $2 million coverage); 7) confirms his or her willingness to 
adhere to the study intervention procedures. For each class series, a back-up 
instructor will also be identified who can teach a class in the event that the primary 
instructor is ill or is unable to teach due to an emergency. 
Group orientation and classes: Similar to the yoga program, the 
stretching/strengthening control program will begin with a group orientation led by a 
physical therapist/trainer, who will provide an overview of the 
stretching/strengthening exercises to be covered in the program. This will be 
followed by 90-minute twice weekly group classes, each with no more than 15 
participants, led by the same therapist/trainer, who will have received in-person 
study-specific training from a study expert physical therapist consultant. Classes will 
be designed to make women comfortable with all exercises by 6 weeks and fully 
confident in performing exercises by 12 weeks. During the COVID-19 pandemic, 
classes may be coverted to remote platforms (i.e., may take the form of interactive 
on-line video-based classes rather than in-person classes). 
Home practice: In addition to attending group classes, women will be asked to 
perform stretching/strengthening exercises at home at least one additional hour per 
week and record the dates and times of practice in a log. Women will receive a 
detailed manual with pictures and descriptions of each stretching/strengthening 
exercise to guide them in home practice, as well as a stretch strap and exercise mat 
to use at home. 
Quality and safety:  Instructors leading physical conditioning classes will be physical 
therapists or trainers who have at least 2 years of experience working with adults of 
a range of ages and have completed dedicated in-person training with Sarah 

 
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Pawlowsky, DPT.  Dr. Pawlowsky will provide quality monitoring and assess 
women’s success in learning stretching/strengthening exercises by making an in-
person visit to at least one class in each series. She will also lead twice monthly 
conference calls with instructors, similar to quality monitoring for the yoga program.  
Post-intervention program continuation: After the end of the main 12-week 
intervention period, participants will be encouraged to continue practice 
stretching/strengthening exercises at least two hours per week at home, although 
group intervention classes will no longer be offered through the study. 
5.3 
Concomitant Interventions  
5.3.1 Required Interventions 
Participants in both intervention groups will also receive a pamphlet at the 
Baseline Clinic Visit that provides basic patient-directed information about 
first-line behavioral self-management of incontinence, including pelvic muscle 
exercises, timed urination, and urge suppression. This pamphlet is consistent 
with usual care of incontinence in the general community, and has been used 
in previous studies of experimental treatments for incontinence conducted by 
the investigators.45 Participants will be queried about use of these techniques 
at baseline, at the 6-week and 12-week clinic visits, and as part of the 12- 
and 24-week post-intervention assessment, so that information about co-
interventions can be incorporated into data analyses if appropriate. 
Since information about behavioral self-management of incontinence is 
available from multiple websites and public resources, systematic provision of 
this information will help avoid differential use of self-management techniques 
between treatment groups, and will also reflect expected concomitant use of 
these techniques with yoga in clinical practice.  However, participants will be 
discouraged from pursuing more formal training or coaching in behavioral 
incontinence treatment strategies from pelvic floor physical therapists or other 
specialized healthcare practitioners during the trial intervention period (see 
prohibited interventions below). 
5.3.2 Prohibited or Discouraged Interventions 
Participants will be asked to refrain from using other standard clinical 
treatments for incontinence during the 12-week intervention period. These 
include medications with the potential to affect incontinence (anticholinergic 
bladder medications, tricyclic antidepressants, mirabegron), invasive or 
surgical bladder treatments, nerve stimulation therapy, medical devices used 
to improve bladder symptoms (e.g., pessary), and behavioral treatment 
programs administered by certified practitioners (e.g., pelvic floor 
rehabilitation therapy, biofeedback programs).  
Participants will be queried about use of these treatments at baseline, at the 
6-week and 12-week clinic visits. If participants are found to be using these 
treatments during the 12-week study intervention period, they will not be 
required to terminate the study early, but use of outside treatment will be 
recorded as a protocol deviation, and information about use of these 
additional treatments may be taken into account in per protocol data 
analyses.  

 
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During the during the 12- and 24-week post-intervention follow-up periods, 
participants will also be encouraged to avoid using other clinical treatments 
for incontinence, and instead focus on continued home practice of study yoga 
or muscle stretching/strengthening exercises to manage their symptoms. 
Participants will be queried about use of these treatments at the 12- and 24-
week follow-up assessments, so that information about use of these 
treatments can be incorporated into data analyses. However, use of other 
clinical incontinence treatments during the 12- and 24-week post-intervention 
follow-up periods will not be considered a protocol deviation. 
Additionally, participants will be asked to refrain from starting or changing the 
dosage of medications that could affect depression or anxiety symptoms 
(e.g., antidepressants, sedatives/hypnotics, or antipsychotic agents) during 
the 12-week intervention period or 12- or 24-week post-intervention follow-up 
period, although maintenance of stable dosages of these medications will be 
acceptable. 
5.4 
Adherence Assessment  
Adherence to group yoga and physical conditioning classes will be documented by 
the study class instructors using standardized attendance logs. Attendance logs will 
be returned to clinical coordinators on a weekly basis throughout the 12-week yoga 
and control intervention programs. Clinical coordinators will immediately contact any 
participant who misses a scheduled class to ask about reasons for missing the class, 
reinforce the importance of class attendance, and troubleshoot any barriers to 
attendance. 
Adherence to home practice of yoga or stretching/strengthening exercises will be 
tracked using home practice logs. Participants will be instructed to record the date, 
time, and duration of each home practice session in their logs, as well as the specific 
yoga poses or stretching/strengthening exercises practiced during each session.  
Home practice logs will be returned to the clinical coordinators on a weekly basis 
during the 12-week intervention programs. Clinical coordinators will contact any 
participant whose log indicates that she is not practicing yoga or 
stretching/strengthening exercises at least one hour a week at home. Additionally, 
home practice logs will be returned 12 and 24 weeks after the end of the intervention 
program to assess home practice during the post-intervention follow-up period. 
Every effort will be made to encourage participants to complete all intervention 
classes and practice sessions. Prior to randomization, study coordinators will stress 
the importance of adherence to group classes and home practice, and only those 
women who indicate that they are available on scheduled class dates and willing to 
practice yoga or stretching/strengthening exercises at home as recommended will be 
eligible for randomization. The importance of adherence will again be stressed at the 
orientation sessions for each intervention class series, as well as during follow-up 
telephone calls at 2 weeks and a follow-up visit at 6 weeks. Additionally, attendance 
sheets from yoga and stretching/strengthening classes will be carefully monitored, 
and home practice logs will be reviewed weekly, so that study staff can immediately 
call any women who miss classes or fail to document home practice in order to 
reinforce the importance of attendance/practice and troubleshoot barriers to 
adherence. 

 
20 of 54 
 
 
 
6.  STUDY PROCEDURES  
6.1 
Study Measures 
6.1.1  Urinary Incontinence 
The primary efficacy outcome, frequency of any urinary incontinence, will be 
assessed using a 3-day voiding diary that has been shown to be a valid and 
reliable method for documenting change in incontinence symptoms and is 
widely used in clinical trials of incontinence treatments.46,47  At 
screening/baseline, 6 weeks, 12 weeks, and 12- and 24- weeks after the end 
of the yoga and control intervention programs (i.e., 24 and 36 weeks), each 
participant will receive written instructions and a blank diary to take home, and 
will use the diary to record all voiding and incontinence episodes over a 3-day 
period and classify incontinence episodes by clinical type (urgency, stress, 
other). Upon return of the diary, an analyst will abstract data to determine the 
number of total as well as urgency and stress incontinence episodes per day. 
For diaries that are completed after randomization, data will be abstracted by 
an analyst who is blinded to treatment assignment. 
6.1.2  Incontinence-Related Quality of Life  
To address incontinence-related quality of life, participants will complete the 
following validated questionnaire measures at baseline, 6 weeks, and 12 
weeks, as well as 12 and 24 weeks after the end of the yoga and 
stretching/strengthening control programs: 
A. Incontinence Impact Questionnaire (IIQ)-- a validated, 28-item measure of 
the impact of incontinence on 4 domains of functioning and quality of life 
(physical activity, emotional health, relationships, and travel).48,49 Scores 
range from 0 to 100; higher scores indicate worse impact.  
B.  Urogenital Distress Inventory-6 (UDI-6)-- a validated, 6-item measure that 
assesses subjective distress from frequent urination, urgency 
incontinence, stress incontinence, small-volume leakage, difficulty 
emptying the bladder, and genital pain.49 Scores are scaled from 0 to 100. 
C. Patient Perception of Bladder Condition (PPBC)-- a validated single-item 
measure assessing the degree to which respondents consider their 
condition to be a problem on a 6-point scale.50,51 
D.  Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised 
(PISQ-IR)- a validated 20-item measure of sexual function in women with 
pelvic floor disorders (PFDs), designed to be appropriate for both sexually 
active and inactive women.52 
6.1.3  Depression, Anxiety, and Perceived Stress  
To evaluate depression, anxiety, and perceived stress symptoms that may be 
associated with incontinence, participants will complete the following validated 
questionnaire measures at screening/baseline, 6 weeks, and 12 weeks, as 
well as 12 and 24 weeks after the end of the yoga and control intervention 
programs: 
A. Center for Epidemiologic Studies Depression Scale (CES-D): Depressive 
symptoms will be assessed by the CES-D, a 20-item measure that has 
been widely used in clinical trials, including bladder interventions, and is 
sensitive to change.53 Total scores range from 0 to 60. 

 
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B. Spielberger State Trait Anxiety Inventory (STAI): Somatic anxiety (i.e., the 
affective component of anxiety believed to be related to autonomic 
physiological arousal response) will be measured using the trait 
component of the STAI, a 20-item self-administered measure validated in 
clinical populations, including patients with bladder symptoms, with scores 
ranging form 20 to 80.54,55 
C. Hospital Anxiety and Depression Scale (HADS): Cognitive anxiety (i.e., the 
mental component of anxiety associated with fear of failure) will be 
measured by the HADS, a validated self-administered questionnaire that 
includes a 7-item Anxiety Subscale56 shown to be sensitive to change in 
incontinence trials.57 Scores range from 0 to 21, with higher scores 
indicating greater anxiety. 
D. Perceived Stress Scale (PSS): Perceived stress will be assessed by the 
PSS, a 10-item measure of thoughts and feelings related to perceived 
stress in the past month, validated in a probability sample of the United 
States.58 Scores range from 0 to 40; higher scores indicated greater 
stress. 
6.1.4  Yoga/Physical Conditioning Self-efficacy and Competency 
A. Yoga Posture Self-Efficacy: After randomization, 6 weeks, and 12 weeks, 
women in the yoga group will complete a structured questionnaire 
(modeled after an existing self-efficacy measure 59 and pre-tested in the 
investigators’ previous pilot study) to indicate how confident they are that 
they can perform each of the postures featured in the program (from ‘not at 
all’ to ‘extremely confident’). A corresponding questionnaire will be 
administered to the muscle stretching/strengthening control group 
participants. 
B. Independent Yoga Competency Assessment: To provide a more objective 
assessment of women’s success in learning yoga, a yoga expert 
consultant will attend one class at the end of each series and observe 
women as they practice yoga. The consultant will rate each woman’s 
success in performing each yoga posture on a 5-point scale, ranging from 
“not at all” to “extremely” successful. In the muscle 
stretching/strengthening control group, a study expert physical therapist 
consultant will provide similar assessments. 
C. Yoga Practice Adherence Self-Efficacy: After randomization, 6 weeks and 
12 weeks, as well 12 and 24 weeks after the end of the intervention 
programs, women will complete a measure of confidence in adhering to 
yoga or stretching practice, modeled after existing physical activity 
adherence self-efficacy scales 60 and tested in the pilot study. Women will 
indicate on a 5-point scale how confident they are that they can practice 
yoga or stretching when they: 1) are tired, 2) are in a bad mood, 3) have 
limited time, 4) are away from home, and 5) are not regularly attending 
yoga classes. Scores will range from 0 to 20. 
D. Credibility and Expectations of Treatment: To assess whether women 
perceive the yoga and physical conditioning interventions as equally 
credible and have similar expectations for improvement in incontinence, 
we will administer a modified version of an expectancy/credibility measure 
used in other women’s health studies at baseline.61 

 
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6.1.5  Physical Function/Performance Measures  
To guide exploration of changes in physical function/conditioning as a 
potential mediator of intervention effects in women with incontinence, 
participants will complete the following assessments at baseline, 6 weeks, and 
12 weeks:  
A. PROMIS Adult Physical Function Profile short-form: This self-administered 
questionnaire measure of perceived physical function assesses functioning 
of the upper extremities, lower extremities, and central regions (neck, back), 
and has previously been validated across age and race-ethnicity groups.62   
B. Balance testing: Participants will be asked to undergo successive semi-
tandem, tandem, and one-legged balance stand tests, in which their ability 
to hold each position for up to 30 seconds will be assessed.63,64  
C. 30-second chair stand: Participants will be asked to stand up from a 
standard chair to a fully extended standing position as many times as 
possible within 30 seconds with their arms folded across their chest. The 
number of completed repetitions achieved in 30 seconds will be recorded, 
with higher number indicating more strength or power.65 
D. 2-minute step test: In this test of aerobic endurance for older adults,69,70 
participants subjects are asked to step in place as many times as possible 
in a 2 minute period, each time raising the knee to a level midway between 
the patella and iliac crest. Higher scores indicating greater fitness. 
6.1.6  Cardiac Autonomic Function Measures  
To guide exploration of changes in autonomic nervous system function as a 
potential mediator of intervention effects in women with incontinence, 
participants will undergo the following measures at baseline and 12 weeks. 
During the COVID-19 pandemic, participants may decline to undergo these 
measurements that require them to come into close proximity (less than 6 foot 
distance) with study personnel. 
 
A. High frequency heart rate variability (a.k.a. respiratory sinus arrhythmia, or 
RSA) refers to the degree to which heart rate accelerates and decelerates 
during the respiratory cycle, and has been shown to be a reliable marker 
of cardiac parasympathetic activity.71-73 Evaluation of rest-to-stress 
changes in RSA allows for assessment of abnormalities in adaptive vagal 
regulation, previously shown to be associated with bladder instability and 
urine leakage in response to stressful events.20-22 Procedures for 
assessing RSA, monitoring data quality, and interpreting findings have 
been designed by co-investigator Wendy Mendes, PhD, who has authored 
one of the main textbooks on autonomic assessment,74 published four 
methodological articles and chapters on this topic,75-78 and collaborated 
with the research team on other NIH-funded studies.79 Heart rate variability 
measurements will be obtained according to standard protocols from the 
North American Society of Pacing & Electrophysiology,80 in which two 
ECG electrodes will be attached to each participant’s right and left wrists 
using pre-gelled sensors while in the seated position. Following an initial 
10-minute “resting” recording, a 10-minute “stress” recording will be 
obtained while the participant completes two stress tasks, including a 
visual attention and tracking task81 shown to reliably induce vagal 

 
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withdrawal in subjects across the lifespan.75,76  Analyses using Mindware 
software will examine both resting and rest-to-stress change in RSA. 
B. Systolic pre-ejection period (i.e., PEP, the time period between the left 
ventricle contracting and the aortic valve opening) will be examined as an 
established measure of sympathetic activity that can be measured non-
invasively using impedance cardiography.72,73 For this study, PEP will be 
measured using the impedance cardiography module of the same Biopac 
MP100 system used to assess RSA above.  According to established 
protocols82 also used in other NIH-funded studies by the team,79 a 
standard tetrapolar band electrode system will be attached to each 
participant while in the seated position (two inner electrodes placed at the 
xiphisternal joint and the base of the neck, outer electrodes placed 3 cm 
distally to the inner electrodes) and connected to the impedance 
cardiograph module. Impedance cardiogram recordings will be obtained 
over the same time interval as RSA recordings, including a resting period 
and a stress period. This will include a computer-based stress task 
designed by co-investigator Dr. Mendes to assess sympathetic reactivity,83 
which participants must complete with limited instruction and under time 
constraints. Analyses using Mindware software will examine both resting 
and rest-to-stress change in PEP. 
6.1.7  Pelvic Floor Muscle Strength  
To guide exploration of changes in pelvic floor muscle strength as a potential 
mediator of intervention effects in women with incontinence, participants will 
be invited to undergo the following optional assessment of pelvic floor muscle 
strength at baseline and 12 weeks. For this assessment, a clinically-trained 
assessor (doctor, nurse, or pelvic floor physical therapist) will perform a digital 
pelvic exam and ask the participant to squeeze her pelvic floor muscles during 
exam. The assessor will then rate pelvic muscle strength using the Brink 
scale, which includes 4-point scales in 3 categories—contraction pressure, 
displacement of the examiner’s fingers, and duration of squeeze— to create 
an overall score of 0 to 12.84-90 Since this is an optional assessment, 
participants who have a relative contraindication to pelvic exam or anticipate 
pain with pelvic exam can decline to undergo this measurement. During the 
COVID-19 pandemic, participants may also decline to undergo these 
measurements that require them to come into close proximity (less than 6 foot 
distance) with study personnel. For assessments performed after 
randomization, the assessor will be blinded to intervention assignment. 
 
At the Stanford clinical site, participants will also be invited to undergo 
perineometer assessment of pelvic floor muscle strength by a board-certified 
urogynecologist at the same timepoints (baseline and 12 weeks). Participants 
will be asked to contract their pelvic floor muscles, and contraction strength 
will be measured with a Laborie Urostym digital perineometer. This device is 
currently used clinically and approved for pelvic floor physical therapy and 
biofeedback. Measurements obtained by perineometer have previously been 
shown to have good inter-rater and test-retest reliability. Measurements will 
include minimum, maximum, and average strength of each pelvic floor muscle 
contraction measured. Duration of contraction will also be recorded. A total of 
three contractions will be measured by digital perineometry. Measurements 

 
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will be recorded in cm H2O or mm Hg. Each patient will be assigned a vaginal 
sensor that will be processed according to manufacturer’s recommendation 
and used for the baseline and follow-up exams. Since this is an optional 
assessment, participants who have a relative contraindication to pelvic exam 
or anticipate pain with pelvic exam can decline to undergo this measurement. 
 
6.1.8  Additional Screening and Covariate Measures  
The following data will be collected to assess eligibility, assess whether 
treatment groups are comparable at baseline, and guide statistical adjustments 
in the event groups are not balanced: 
A. Demographic history including date of birth, gender/sex identity, 
race/ethnicity, education history, employment history, marital status 
(screening/baseline) 
B. Urologic/urogynecologic history including age of onset of incontinence, past 
and current treatment of incontinence, history of pelvic surgery, history of 
pregnancy and delivery, menstrual/menopausal status, sexual activity 
status (screening/baseline) 
C. General medical history including general health assessed by the CDC 
Healthy Days module,91 selected medical conditions associated with 
incontinence such as diabetes, tobacco and alcohol use, and physical 
activity level (screening)  
D. Current medication use (screening/baseline and 12 weeks) 
E. Health-related habits such as tobacco/alcohol use (screening); fluid and 
caffeine intake using the fluid intake amount and fluid intake behavior 
sections of the Questionnaire-Based Voiding Diary92-94 (baseline, 6 weeks, 
12 weeks, and 12 and 24 weeks post-intervention); prior yoga experience, 
prior group-based physical activity instruction (screening), physical activity 
level by the International Physical Activity Questionnaire95,96 (screening) 
F. Sleep function assessed using the Pittsburgh Sleep Quality Index (PSQI),97,98 
a validated questionnaire evaluating sleep quality, latency, efficiency, and 
problems, and a the Pittsburgh Sleep Diary, a daily self-report measure of 
sleep duration and disruption used to enhance or complement data 
obtained from actigraphy in multiple past studies of older adults99-101 
(baseline, 6 weeks, and 12 weeks, as well as 12 and 24 weeks after the end of 
intervention programs). 
G. Physical exam measures including measured height, weight, heart rate, and 
blood pressure (screening/baseline and 12 weeks) 
6.2 
Evaluations  
6.2.1 Screening Evaluations 
Screening evaluations will be conducted by study coordinators based at 
outpatient facilities affiliated with UCSF or Stanford University.  Screening 
procedures will include a brief preliminary Screening Telephone Interview, 
followed by an in-person Screening Clinic Visit, completion of a 3-day voiding 
diary at home, and review of the diary at an in-person Baseline Clinic Visit. All 
screening procedures must be completed within a 90-day period in order for 
participants to be eligible for randomization.  If screening procedures cannot 
be completed within 90 days, initial screening procedures must be repeated 

 
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to ensure that participant eligibility has not changed prior to randomization. 
6.2.2   Consenting Procedure 
Prior to administration of any data collection instruments, signed consent will 
be obtained by a research coordinator at the beginning of the Screening 
Clinic Visit. A single informed consent process will be used that will cover 
both the screening and post-randomization procedures. All participants must 
be able to read and understand the consent form in English and must provide 
written informed consent before enrolling in the study. Following the UCSF 
IRB-approved template, the consent form will describe the purpose of the 
study, the procedures involved in recruiting, randomized, and monitoring 
participants, and the potential risks and benefits associated with participation.  
A study coordinator will first explain the study procedures to the potential 
participant, referring as necessary to the detailed IRB-approved consent 
form. The coordinator will then give a copy of the consent form to the 
potential participant to read. After the potential participant has read the 
consent form, she will be asked if she has any questions or concerns about 
the study. Once these questions/concerns have been addressed, the 
participant will be asked to sign the consent form, and will be given a copy of 
the consent form to take home for future reference.  
Pursuant to California Health & Safety Code 24172, each participant will also 
receive a copy of the Experimental Subject's Bill of Rights.  
6.2.3   Screening Procedures 
Telephone Screening Interview 
• Women who call in response to recruitment advertisements or who have 
previously given permission to be contacted about opportunities to 
participate in women’s health research at UCSF will be provided with a 
brief overview of the study goals and procedures by a clinical coordinator 
over the telephone. 
• If interested, candidates will complete a brief telephone survey to assess 
preliminary eligibility (including age, gender, duration/frequency/type of 
incontinence, current and past incontinence treatment, prior yoga and 
muscle strengthening exercise practice, physical mobility, exclusionary 
conditions and medications, availability for upcoming group intervention 
classes). 
 
Screening Clinic Visit 
• At this visit, a clinical coordinator will explain the requirements of the study 
while referring to the detailed informed consent form, and candidates will 
provide written informed consent if they are still interested in proceeding 
with the study. 
• Candidates will complete questionnaires about their demographic, 
urologic/urogynecologic, and medical history to determine if they meet 
criteria related to age, gender, duration/frequency/type of incontinence, 
current and past incontinence treatment, prior yoga and muscle 
strengthening exercise practice, exclusionary conditions, and medications 
• Over-the-counter and prescription medications will be reviewed to 
determine if candidates are taking any exclusionary medications. 

 
26 of 54 
 
 
 
• Height, weight, and resting blood pressure and pulse measurements will 
be obtained. 
• Basic physical mobility including ability to rise from a supine to standing 
position will be assessed. 
• A clean-catch urine sample will be collected to assess for possible urinary 
tract infection and rule out pregnancy (for candidates who are still of child-
bearing potential).   
• Potentially eligible women will be instructed on completing a 3-day voiding 
diary to document all incontinence and voiding episodes at home. 
• A Baseline Clinic Visit will be scheduled at least 3 days later for review of 
the completed voiding diary and determination of final eligibility. 
 
Baseline Clinic Visit 
• Candidates will return with the completed voiding diary, and results will be 
reviewed by a clinical coordinator. Candidates whose diaries indicate 
predominantly urgency, stress, or mixed-type incontinence, document at 
least 3 incontinence episodes per 3-day diary, and meet all other eligibility 
criteria will be eligible to continue.   
• Women will complete structured questionnaires about depression and 
anxiety, incontinence-specific quality of life, and sleep quality.   
• Physical function will be assessed by questionnaire as well as direct 
physical performance testing. 
• Cardiac autonomic function will be assessed through heart rate variability 
and impedance cardiography measurements. 
• Participants will be invited to undergo pelvic floor muscle strength 
assessments involving a digital pelvic exam (and/or perineometer 
assessment if the visit is at the Stanford site). The assessment may be 
performed directly during the Baseline Visit, or an alternate clinic 
assessment may be scheduled specifically for this exam. 
• Participants will be given a brief written pamphlet about usual first-line 
behavioral management of incontinence (see description in interventions 
section above).  
• If the Baseline Clinic Visit takes place within 2 weeks of the start of the first 
intervention program session, eligible participants will be randomized to 
one of the two interventions at this visit. 
• If the Baseline Clinic Visit takes place more than 2 weeks before the first 
intervention program session, eligible participants will be scheduled for a 
Randomization Telephone Call within two weeks of the start of the 
program to determine their intervention assignment. 
6.2.4 Randomization and Blinding 
Randomization 
Women who are confirmed to be eligible and available to take part in 
upcoming group intervention class series will be randomized in a 1:1 ratio to 
one of the two intervention groups. Randomization will ideally take place 
within 1 month of completion of screening procedures, and in no cases will be 
able to take place more than 2 months after completion of screening 
procedures. Randomization must also take place within 2 weeks of the start 
of the relevant group intervention class series. If the Baseline Clinic Visit 
occurs within 2 weeks of the start of the intervention program, eligible 

 
27 of 54 
 
 
 
participants will be randomized to one of the two interventions directly at this 
visit. If the Baseline Clinic Visit occurs more than 2 weeks before the start of 
the intervention program, eligible participants will be scheduled for a 
Randomization Telephone Call within two weeks of the start of the program to 
determine their intervention assignment. 
During the Baseline Clinic visit or during the Randomization Telephone Call 
(whichever is appropriate), randomization will be performed according to a 
pre-established computer-algorithm using randomly permuted blocks of sizes 
2, and 4.  Randomization will be stratified by clinical type of incontinence (i.e., 
stress-predominant, urgency-predominant) to ensure adequacy of 
randomization among women with each major incontinence type. Prior to 
randomization, the research coordinator will complete a randomization 
checklist confirming that the participant meets all eligibility criteria. 
Additionally, participants’ availability and willingness to attend upcoming yoga 
or control group classes will be re-confirmed before randomization 
assignment is obtained. 
Standard allocation concealment procedures will be followed to avoid 
manipulation of randomization.102 Prior to the start of recruitment, the 
randomization scheme will be developed by a statistical programmer who will 
have no contact with participants or role in data entry, cleaning, or analysis.  
To execute the randomization scheme, a research assistant who will also 
have no contact with participants or access to study data will then prepare a 
series of sealed, opaque envelopes containing group assignment, numbered 
consecutively with the randomization sequence numbers. When the 
participant is ready for randomization, study coordinators will enter the date, 
participant name, and study ID in the randomization log and select the next 
numbered envelope corresponding to the participants’ type of incontinence to 
determine group assignment. Once a participant has been randomized, she 
cannot be re-assigned to a different intervention group. All randomization 
envelopes will be retained for review; randomization dates and times should 
follow the order of the sequence numbers, providing a check on validity.  
After randomization, participants will complete self-efficacy questionnaires 
specific to their assigned intervention (yoga or stretching/strengthening). 
Blinding 
Although participants cannot be blinded to intervention assignment (due to 
the behavioral nature of the interventions), study procedures have been 
carefully designed to avoid bias associated with knowledge of group 
assignment.  First, to minimize differential expectations of treatment success, 
participants will be told that they are participating in a study of two different 
types of low-impact group activity-based interventions to enhance self-
management of incontinence, and that we do not know which is more 
effective (which is true). The primary outcome will be assessed by voiding 
diaries, a measure that is resistant to reporting bias, and data from returned 
diaries will be abstracted by blinded analysts. Similarly, data from participant 
follow-up questionnaires assessing other symptom and quality-of-life 
outcomes associated with incontinence will be abstracted by blinded 
analysts.   
Only study personnel who are involved in delivering the therapeutic 
interventions, assessing and promoting adherence to these interventions, 

 
28 of 54 
 
 
 
and/or monitoring adverse events related to these interventions will be aware 
of group assignment. All investigators, study analysts involved in abstracting 
efficacy outcomes data, and statistical programmers involved in ongoing data 
cleaning will be blinded to treatment allocation. Unless stipulated by the Data 
and Safety Monitor or required to assist with the clinical management of a 
participant experiencing a serious adverse event, these investigators and 
staff will remain blinded until after all participants have completed the 12-
week clinic visit, trial data from the 12-week visit are edited and cleaned, and 
the trial dataset for the 12-week intervention period is locked.     
6.2.5 Follow-up/Final Evaluations 
Follow-up evaluations will consist of a 2-week telephone call, 6-week clinic 
visit, 9-week telephone call, 12-week clinic visit, and 24-week mail-in 
assessment: 
2-Week Telephone Call  
• 
Two weeks after the start of the yoga or control program, coordinators will 
call women to assess adverse events, address any concerns, and 
reinforce adherence to group classes and home practice of yoga or 
stretching/strengthening exercises.   
• 
Adherence to and challenges in performing usual behavioral self-
management strategies for incontinence will also be assessed.   
• 
Women will be reminded to continue recording home yoga or 
stretching/strengthening practice in their practice logs and return their 
logs each week to the yoga class instructors. They will also be reminded 
to start filling out a second voiding diary 3 days before the 6-Week Clinic 
Visit. 
 
6-Week Clinic Visit 
• 
Six weeks after the start of the yoga or control program, women will return 
for a follow-up visit, bringing their second completed voiding diary.  
• 
Voiding diaries will be retrieved by the research coordinator and delivered 
to a blinded analyst for data abstraction.  
• 
Adverse events will be recorded using standardized forms (see safety 
monitoring section).   
• 
Adherence to yoga or stretching/strengthening practice and incontinence 
self-management strategies will be re-assessed.   
• 
Yoga and stretching/strengthening self-efficacy questionnaire measures 
will be administered.    
• 
Participants will re-self-administer questionnaires about incontinence-
related quality of life, depression and anxiety symptoms, and sleep 
quality.  
• 
Participants will be asked about their use of other strategies to manage 
their incontinence. 
• 
Physical function will be assessed by questionnaire as well as direct 
physical performance testing. 
• 
Current use of prescription and over-the-counter medications will be re-
reviewed. 
• 
Women will be given a third voiding diary to complete before the 12-week 
visit, and the 12-week visit will be scheduled. 

 
29 of 54 
 
 
 
 
9-Week Telephone Call  
• 
Nine weeks after the start of the yoga or control program, coordinators 
will call women to assess adverse events, address any concerns, and 
reinforce adherence to group classes and home practice of yoga or 
stretching/strengthening exercises.   
• 
Adherence to and challenges in performing usual behavioral self-
management strategies for incontinence will also be assessed.   
• 
Women will be reminded to continue recording home yoga or 
stretching/strengthening practice in their practice logs and return their 
logs each week to the yoga class instructors. They will also be reminded 
to start filling out a third voiding diary 3 days before the 12-Week Clinic 
Visit. 
 
12-Week Clinic Visit 
• 
Twelve weeks after the start of the yoga or control program, women will 
return for another clinic visit, bringing their third completed voiding diary.  
• 
Voiding diaries will be retrieved by the research coordinator and delivered 
to a blinded analyst for data abstraction. 
• 
Adverse events will be recorded using standardized forms (see safety 
monitoring section). 
• 
Yoga and stretching/strengthening self-efficacy questionnaire measures 
will be re-administered.     
• 
Participants will re-self-administer questionnaires about incontinence-
related quality of life, depression and anxiety symptoms, and sleep 
quality.  
• 
Physical function will be re-assessed by questionnaire as well as by 
physical performance testing. 
• 
Participants will be asked about their use of other strategies to manage 
their incontinence. 
• 
Cardiac autonomic function will be assessed through heart rate variability 
and impedance cardiography measurements. 
• 
Participants will be invited to undergo pelvic floor muscle strength 
assessments. The assessment may be performed directly during the 12-
Week Clinic Visit, or an alternate clinic assessment may be scheduled 
specifically for this exam. 
• 
Current use of prescription and over-the-counter medications will be re-
reviewed. 
• 
A satisfaction questionnaire will be administered to assess overall 
satisfaction with study procedures and change in incontinence symptoms. 
• 
Women will be encouraged continue practicing yoga or 
stretching/strengthening exercises for at least two hours per week for the 
next 12 weeks and record this practice in their home practice logs. 
• 
As an optional activity, selected participants in the yoga arm may be 
invited to take part in brief qualitative interviews to discuss their barriers 
and facilitators to learning and maintaining practice of yoga after this visit. 
 
24-Week (a.k.a. 3-Month Post-Intervention) Assessment 

 
30 of 54 
 
 
 
• 
Approximately twelve weeks after completion of the intervention 
programs, coordinators will call participants to them to complete their 
fourth voiding diary at home (the blank diary will be mailed in advance to 
participants at home, and participants will return it using a pre-stamped 
and addressed envelope). 
• 
Adverse events will be assessed by telephone, video, or in-person visit 
and recorded using standardized forms (see safety monitoring section). 
• 
Women will also be asked to complete questionnaires addressing 
symptom, quality-of life, and sleep outcomes as well as yoga or 
stretching/strengthening practice adherence and self-efficacy at home 
(questionnaires will be mailed in advance to participants at home, or can 
be completed via an on-line survey). 
• 
Participants will be asked about their continued practice of yoga or 
stretching/strengthening techniques and their use of other strategies to 
manage their incontinence. 
• 
Participants will be asked to mail back home practice diaries documenting 
their continued practice of yoga or stretching/strengthening techniques. 
• 
Women will be encouraged continue practicing yoga or 
stretching/strengthening exercises for at least two hours per week for the 
next 12 weeks and record this practice in their home practice logs. 
 
36-Week (a.k.a. 6-Month Post-Intervention) Assessment 
• 
Approximately 24 weeks after completion of the yoga or control program, 
coordinators will call participants to them to complete their fifth voiding 
diary at home (the blank diary will be mailed in advance to participants at 
home). 
• 
Adverse events will be assessed by telephone, video, or in-person visit 
and recorded using standardized forms (see safety monitoring section). 
• 
Women will also be asked to complete questionnaires addressing 
symptom, quality-of life, and sleep outcomes as well as yoga or 
stretching/strengthening practice adherence and self-efficacy at home 
(questionnaires will be mailed in advance to participants at home, or can 
be completed via an on-line survey). 
• 
Participants will be asked about their continued practice of yoga or 
stretching/strengthening techniques and their use of other strategies to 
manage their incontinence. 
• 
Participants will be asked to mail back home practice diaries documenting 
their continued practice of yoga or stretching/strengthening techniques. 
• 
Women will also be asked to complete a close-out satisfaction 
questionnaire addressing their overall satisfaction with study procedures 
and change in incontinence symptoms (questionnaires will be mailed in 
advance to participants at home, or can be completed via an on-line 
survey). 
 
Recommended time windows for completion each of the post-randomization 
follow-up evaluations will be as follows: 
Follow-Up Assessment 
Time Window 
2-week telephone call 
8 to 20 days after the start of the yoga or 
physical conditioning program 
6-week clinic visit 
36 to 48 days (i.e., 6 weeks +/- 6 days) after 

 
31 of 54 
 
 
 
the start of the yogaor physical conditioning 
program 
9-week telephone call 
57 to 69 days after the start of the yoga 
therapy or physical conditioning program 
12-week clinic visit 
78 to 90 days  (i.e., 12 weeks +/- 6 days) after 
the start of the yogaor physical conditioning 
program 
24-week (i.e., 12-week 
post-intervention) 
telephone and mail-in 
assessment 
Within 189 days (27 weeks) of the start of the 
yoga or stretching/strengthening program 
(allowing time for return of mail-in packet) 
36-week (i.e., 24-week 
post-intervention) 
telephone and mail-in 
assessment 
Within 273 days (39 weeks) of the start of the 
yoga or stretching/strengthening program 
(allowing time for return of mail-in packet) 
6.2.6 Early Termination (also see section below) 
If a participant indicates that she needs or wishes to discontinue all 
participation in the study, then she will be encouraged to complete an Early 
Termination visit. This visit will include as many of the procedures originally 
scheduled to take place at the 12-Week Clinic Visit as possible, including: 
assessment of adverse events; re-administration of questionnaires about 
condition-specific quality of life, depression and anxiety symptoms, and yoga 
or stretching/strengthening self-efficacy; review of current medications; re-
assessment of weight, blood pressure, and heart rate; re-assessment of 
physical function, autonomic function, and pelvic floor strength; and 
administration of a study satisfaction questionnaire. The participant’s reasons 
for terminating participation early will be explored and documented in her file. 
Of note, a participant can discontinue participation in study intervention 
classes or intervention home practice without discontinuing participation in 
the overall study. When possible, participants who decide to stop attending or 
engaging in the study intervention programs will be asked to provide data at 
originally planned outcome assessment timepoints (e.g., at 12 weeks and at 
12 and 24 weeks after the originally planned end of the intervention program).  
In this case, no early termination visit will be performed, but planned outcome 
assessment visits will be completed. 
.

 
32 of 54 
 
 
 
6.2.7  Table of Measures and Procedures 
Summary of Measures and Procedures at Study Visits 
 
 
Screening 
Phone Call 
Screening 
Clinic Visit 
Baseline 
Clinic Visit 
Randomization 
Phone Call 
2/9-Week 
Phone Call 
6-Week 
Clinic Visit 
12-Week 
Clinic Visit 
12 week post-
intervention 
24-week post-
intervention 
Brief telephone screening interview 
X 
 
 
 
 
 
 
 
 
Informed consent  
 
X 
 
 
 
 
 
 
 
Demographic/medical history questionnaires 
 
X 
 
 
 
 
 
 
 
Health-related habits questionnaires 
 
X 
 
 
 
 
 
 
 
Review of current medications 
 
X 
 
 
 
X 
X 
X 
X 
Basic physical mobility testing 
 
X 
 
 
 
 
 
 
 
Height, weight, blood pressure, and pulse 
 
X 
 
 
 
 
X 
 
 
Urine dipstick testing 
 
X 
 
 
 
 
 
 
 
Urine pregnancy testing (if appropriate) 
 
X 
 
 
 
 
 
 
 
Fluid intake and behavior questionnaire 
 
 
X 
 
 
X 
X 
X 
X 
Voiding diary return and review 
 
 
X 
 
 
X 
X 
X 
X 
Review of eligibility and randomization  
 
 
X* 
X* 
 
 
 
 
 
Incontinence self-management pamphlet 
 
 
X 
 
 
 
 
 
 
Assessment of credibility/expectations of treatment 
 
 
 
X 
 
 
 
 
 
Incontinence Impact Questionnaire 
 
 
X 
 
 
X 
X 
X 
X 
Urogenital Distress Inventory-6 
 
 
X 
 
 
X 
X 
X 
X 
Patient Perception of Bladder Condition 
 
 
X 
 
 
X 
X 
X 
X 
PISQ-IR Sexual Function Questionnaire 
 
 
X 
 
 
X 
X 
X 
X 
Center for Epidemiologic Studies Depression Scale 
 
 
X 
 
 
X 
X 
X 
X 
Spielberg State-Trait Anxiety Inventory  
 
 
X 
 
 
X 
X 
X 
X 
Hospital Anxiety and Depression Scale  
 
 
X 
 
 
X 
X 
X 
X 
Perceived Stress Scale  
 
 
X 
 
 
X 
X 
X 
X 
Pittsburg Sleep Quality Index 
 
 
X 
 
 
X 
X 
X 
X 
Perceived physical function assessment 
 
 
X 
 
 
X 
X 
X 
X 
Physical performance testing 
 
 
X 
 
 
X 
X 
 
 
Autonomic measures (RSA and PEP) 
 
 
X 
 
 
 
X 
 
 
Pelvic floor muscle strength assessment 
 
 
X 
 
 
 
X 
 
 
Adverse events assessment 
 
 
 
 
X 
X 
X 
X 
X 
Yoga/stretching posture/exercise self-efficacy 
 
 
 
X 
 
X 
X 
 
 
Yoga/stretching practice self-efficacy questionnaires 
 
 
 
X 
 
X 
X 
X 
X 
Assessment of co-interventions 
 
 
 
 
 
X 
X 
X 
X 
Satisfaction/close-out questionnaire 
 
 
 
 
 
 
X 
 
X 
 
*Randomization will take place at either the Baseline Clinic Visit or the Randomization Phone Call

 
33 of 54 
 
 
 
7. SAFETY ASSESSMENTS  
7.1 
Potential Risks and Protective Measures 
Although participation in this study is not expected to place participants at substantial 
risk of harm, study procedures may be associated with the following risks: 
• 
Yoga Intervention:  Possible risks associated with group yoga instruction and 
home yoga practice include muscle soreness and muscle/ligament strain, or 
other musculoskeletal injury if participants fall or lose their balance while trying to 
practice yoga poses. 
• 
Stretching/Strengthening Control Intervention:  Similar to the yoga intervention, 
possible risks associated with the stretching/strengthening control intervention 
include muscle soreness and muscle/ligament strain, or musculoskeletal injury if 
participants fall or lose their balance while trying to learn or practice the 
stretching or strengthening exercises. 
• 
Behavioral Incontinence Self-Management Pamphlet:  Provision of standard 
written information on usual first-line behavioral self-management strategies for 
incontinence such as pelvic floor muscle exercises and timed urination should 
not pose any risks to participants, although participants may find it inconvenient 
or unpleasant to read the pamphlet. 
• 
Questionnaires and Diaries: Although the information participants provide on 
data collection forms and diaries is confidential, some participants may feel 
embarrassed at having to answer questions, especially those related to urinary 
symptoms, depression, anxiety, or sexual function. There will be slight 
inconvenience in time and effort to complete diaries and questionnaires.  
• 
Physical Exam Measurements:  There are no direct risks associated with 
undergoing measurement of height, weight, blood pressure, or heart rate, 
although participants may experience this as inconvenient or unpleasant. 
• 
Digital Pelvic Examination: Digital pelvic examination (not requiring a speculum) 
and assessment of pelvic floor muscle strength may be associated with 
discomfort or soreness in the perineal or vaginal area, emotional reaction to 
being touched in the genital area, feeling of fullness or pressure in the rectum, or 
urge to urinate during or following the exam. 
• 
Perineometer Assessment: Similar to digital pelvic exam, perineometer 
assessments of pelvic floor muscle strength (at the Stanford site only0 may be 
associated with discomfort or soreness in the perineal or vaginal area, emotional 
reaction to being touched in the genital area, feeling of fullness or pressure in the 
rectum, or urge to urinate during or following the exam. 
• 
Urinalysis and Urine Pregnancy Testing: There are no direct risks associated 
with collection of the clean-catch urine sample, although some participants may 
experience this as inconvenient or unpleasant. 
• 
Heart Rate Variability and Impedance Cardiography:  Heart rate variability and 
impedance cardiography will be obtained using a non-invasive Biopac electronic 
monitoring system.  The only adverse effect that may result from these 
measurements is mild skin irritation at the site of the ECG or cardiac impedance 

 
34 of 54 
 
 
 
electrodes, which should disappear within 24 hours of removing the electrodes.  
Although noninvasive, measurement of heart rate variability and pre-ejection 
period may be experienced by participants as inconvenient or mildly unpleasant. 
To minimize potential risks to participants associated with study interventions and 
procedures, the following steps will be taken: 
• 
Yoga Intervention:  The instructors leading the group yoga classes will be 
trained yoga teachers who will have experience in teaching adults from a wide 
range of ages to learn and practice yoga safely and will undergo specific, in-
person training by the study’s yoga expert consultants.  The study protocol 
incorporates yoga props such as blocks and blankets to help participants 
perform yoga postures in such a way that will minimize the likelihood of muscle 
strain or musculoskeletal injury.  The yoga instruction manuals and audio 
recordings are designed to include explicit tips on modifying or adapting 
postures to accommodate problems with mobility, flexibility, or balance. 
• 
Stretching/Strengthening Intervention:  Instruction for the control intervention 
classes will be provided by trained physical therapists or personal trainers who 
are experienced in teaching patients of all ages to perform physical exercises 
safely, and who will have completed in-person training with co-investigator 
Sarah Pawlowsky, PT. Stretching and strengthening exercises have been 
selected to be appropriate for middle-aged and older women who may have 
flexibility or mobility limitations in addition to incontinence. 
• 
Behavioral Incontinence Self-Management Pamphlet:  The pamphlet used in 
this trial has previously been administered and refined in other large-scale 
research studies. Study coordinators will be available to answer participants’ 
questions about the pamphlet if they arise. 
• 
Questionnaires and Diaries: Any paper-based questionnaires or diaries 
collected in this research will be stored in a locked file cabinet in a locked room 
in research facilities, and data obtained from diaries and questionnaires will be 
stored on password-secured servers. All study staff are fully trained in good 
clinical practice and Human Subject Projections procedures, and the importance 
of participant confidentiality will be emphasized. 
• 
Physical Examination Measures:  Study coordinators who are responsible for 
obtaining physical exam measures will have prior clinical experience with 
performing physical exam measurements in middle-aged and older women, and 
will receiving study-specific training to ensure that they perform measurements 
in a manner that is sensitive and minimizes discomfort to participants. 
• 
Digital Pelvic Examination: Digital pelvic exams and assessment of pelvic floor 
muscle strength will be performed by clinically-trained consultants who have 
experience performing pelvic exams for clinical care and are trained to perform 
exams in a manner that is sensitive and minimizes discomfort to participants. 
Participants will be informed that they can ask to stop the exam for any reason; 
they can also decline the pelvic exam but take part in other aspects of the study. 
• 
Perineometer Assessment: Perineometer-based assessment of pelvic floor 
muscle strength (at the Stanford site only) will be performed by a board-certified 
urogynecologist with experience performing pelvic exams for clinical care, 
experience in perineometry measurements, and training in performing exams in 
a manner that is sensitive and minimizes discomfort to participants. Participants 

 
35 of 54 
 
 
 
will be informed that they can ask to stop the assessment for any reason; they 
can also decline the pelvic exam but take part in other aspects of the study. 
• 
Urinalysis and Pregnancy Testing: Study coordinators who are responsible for 
performing urine testing will be trained to instruct participants on providing urine 
samples in a manner that is sensitive and minimizes embarrassment. 
• 
Heart Rate Variability and Impedance Cardiography:  Participants with a history 
of allergy or adverse reaction to ECG electrodes or adhesives may to forgo 
undergo heart rate variability or impedance cardiography measures.  If 
participants develop a skin reaction after testing is begun, measurements will be 
discontinued, and no further testing will be performed at any future visits. 
7.2 
Methods and Timing of Safety Assessments 
To monitor participant safety, a clinical coordinator will assess for adverse events at 
each follow-up telephone and in-person contact following randomization, starting with 
the 2-Week Telephone Call. Additionally, participants will be given telephone 
numbers to call study staff in between scheduled study visits or calls to report any 
significant health changes. 
Coordinators will not prompt participants to provide information about specific types 
of adverse events at follow-up visits, but instead encourage participants to volunteer 
information by asking the standardized, open-ended question, “Have there been any 
changes in your health since your last visit?”  Any negative changes in health 
reported by participants will then be recorded on standardized AE or SAE forms, as 
appropriate (see below for definitions and documentation). 
7.3     Adverse Events and Serious Adverse Events    
7.3.1  AE/SAE Definitions  
An Adverse Event (AE) is any untoward medical occurrence in participant that 
occurs during the study or with use of the study interventions. An adverse 
finding can include a sign, symptom, abnormal assessment, or any 
combination of these. Medical conditions or diseases present before starting 
study interventions will only be considered adverse events if they worsen 
after starting the intervention. 
A Serious Adverse Event (SAE) is any AE that results in death, a life-
threatening event, inpatient hospitalization or prolongation of existing 
hospitalization, a persistent or significant disability/incapacity, a congenital 
anomaly or birth defect, or any other important medical event that jeopardizes 
the safety of participants based upon appropriate medical judgment. 
7.3.2  AE/SAE Documentation 
All negative changes in health reported by participants will be recorded on 
standardized AE or SAE forms, as appropriate. Each adverse event will be 
assigned an AE number and will be recorded on a separate AE form to avoid 
duplication in reporting. For each AE, clinical coordinators will record the date 
of onset and resolution of the AE and record the nature or type of AE.  In 
consultation with the principal investigator, coordinators will also indicate 
whether any indicate whether any specific action such as discontinuation of 
the study intervention was taken in response to the AE.   

 
36 of 54 
 
 
 
Using the Common Terminology Criteria for Adverse Events (CTCAE) 
system, all adverse events will be graded in severity using the 5-point CTCAE 
scale. According to this scale, AEs are considered grade 1 if they represent 
only mild symptoms or asymptomatic laboratory findings; grade 2 if they 
cause moderate symptoms that limit instrumental activities of daily living 
(shopping, transportation, household tasks); grade 3 if they are serious or 
disabling events or result in hospitalization or prolongation of hospitalization 
without being directly life-threatening; grade 4 if they are life-threatening 
events in which the participant is at risk of death at the time of the event if 
immediate intervention is not undertaken; or grade 5 if they are fatal adverse 
events. 
Each serious adverse event will be assigned an SAE number and recorded 
on an SAE form.  Similar to regular AEs, clinical coordinators will record the 
date of onset and resolution of each SAE and record the nature or type of 
SAE. Coordinators will also document any treatment provided for the SAE, 
indicate any laboratory or other clinical data obtained about the SAE, indicate 
the participant’s condition at the time of reporting of the SAE, and indicate 
whether any specific action such as study discontinuation was taken in 
response to the SAE. Each SAE form will be reviewed and signed by the 
principal investigator, who will use a standard attribution scale to indicate the 
potential relationship between any SAEs and study interventions (not, 
unlikely, possible, probably, or definitely related to study intervention). 
7.4 
Reporting Procedures 
 
 
7.4.1   SAE Reporting 
• 
Clinical coordinators will notify the principal investigator immediately when 
a SAE is discovered, in addition to filling out a standardized SAE form 
that will be reviewed and signed by the principal investigator (see section 
above regarding SAE documentation). 
• 
The principal investigator will then report any deaths to the institutional 
review board at the University of California San Francisco, the 
independent Data and Safety Monitor (DSM), and the NIDDK program 
officer within 24 hours of awareness of the event.   
• 
Other unexpected serious adverse events that are potentially 
intervention-related will be reported by the principal investigator to the 
UCSF IRB, the DSM, and the NIDDK Program Officer within 48 hours of 
learning of the event.  
• 
Anticipated or unrelated SAEs will be handled in a less urgent manner but 
will also be reported to the UCSF IRB and the DSM within 1 week of 
awareness of the event, and at least quarterly to the NIDDK Program 
Officer.  Of note, no SAEs that are directly related to the study procedures 
are currently anticipated. 
 
7.4.2   Non-Serious AE Reporting 
 
• 
If a clinical coordinator discovers an AE that does not meet the definition 
of a SAE but may still pose a substantial risk of harm to a participant and 
is potentially associated with study interventions or procedures, he/she 

 
37 of 54 
 
 
 
will report the AE to the principal investigator within 1 working day, in 
addition to filling out a standardized AE form. 
• 
Cumulative trends in all non-serious adverse events will be reviewed by 
the principal investigator and the DSM at scheduled DSM meetings (see 
below for DSM meeting schedule). More frequent cumulative review of 
non-serious adverse events may be performed if recommended by the 
DSM or desired by the principal investigator.  
• 
Although the UCSF IRB does not require reporting of non-serious AEs to 
the UCSF IRB, the principal investigator may consult the UCSF IRB for 
input on handling of non-serious AEs if they may still pose a substantial 
risk of harm to a participant or are potentially associated with study 
interventions or procedures.   
7.5 
Follow-up for AEs/SAEs 
From the time that they are first reported by participants until the end of the study, 
AEs and SAEs will be followed until resolved or considered stable. At each 
scheduled follow-up contact after initial discovery of an AE or SAE, a clinical 
coordinator will assess whether the AE or SAE is continuing or has resolved, and will 
update information about event status on the AE or SAE form, as appropriate. For 
SAEs, the clinical coordinator or principal investigator will also make more active 
attempts to communicate with participants in between scheduled study visits (with 
their permission) in order to monitor resolution of SAEs.   
7.6 
Independent Safety Monitoring  
The conduct of the study and safety of participants will be evaluated by an 
independent Data and Safety Monitor (DSM), who will be a clinical researcher 
experienced with designing, implementing, and monitoring safety in therapeutic 
interventions studies as well as a practicing clinician. The DSM is independent of the 
investigators and staff participating in the study, and has no financial ties to the 
outcome of the study. The DSM will periodically review the conduct and outcomes of 
the study and provide feedback to the investigators, with particular attention to 
protecting the safety of the participants. 
Prior to initiation of the trial, the DSM will review and approve the study design and 
plans for recruitment, adherence, interventions, data quality, and safety monitoring.  
Approximately twice a year after recruitment begins, the DSM will evaluate the 
adequacy and timeliness of participant recruitment, adherence to the protocol, and 
the potential of the study to meet the stated goals; evaluate the quality and integrity 
of the data, including adequacy of data management and data security procedures; 
evaluate participant safety including trends in adverse events and relationship to the 
study procedures; consider factors external to the study when relevant information, 
such as scientific developments, may have an impact on the safety of the 
participants or the ethical conduct of the study; and make recommendations, if 
necessary, to the investigators and the NIDDK on continuation, termination, or other 
modifications of the study protocol. 
The DSM will periodically review aggregate trial data according to the Data and 
Safety Monitoring Plan (DSMP).  An emergency meeting may also be called by the 
principal investigator at any time should questions of participant safety arise.  Each 
review will include an assessment of the adequacy and timeliness of participant 
recruitment, adherence to the visit and intervention protocols, data quality and 

 
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timeliness, adverse effects, and participant safety.  Interim reports for the DSM will 
be prepared by a biostatistician contracted by the Women’s Health Clinical Research 
Center, and sent to the DSM at least 5 days prior to a pre-scheduled meeting or 
conference call.  
After each interim review, the DSM will provide a signed statement that indicates 
whether the study should continue, terminate, or be altered based on ability to meet 
study recruitment and data quality goals and participant safety. He will include any 
recommendations for changes to the protocol if necessary to enhance participant 
safety or potentiate the ability of the trial to answer the research hypotheses.  This 
statement will be provided to the principal investigator and will be sent to the UCSF 
IRB and to the NIDDK program officer.  All materials, discussions, and proceedings 
of the DSM process will be completely confidential.   
8.   INTERVENTION DISCONTINUATION  
Participation in the yoga and/or control interventions may be discontinued if determined to 
be necessary to protect the safety of a participant.  The decision to discontinue participation 
in therapeutic interventions will be made on a case-by-case by the principal investigator, 
with input from the DSM if needed. Possible reasons for discontinuation of the therapeutic 
intervention may include: 1) development of a clinically significant adverse event limiting a 
participant’s ability to safety take part in yoga or stretching/strengthening practice; 2) 
disruptive behavior exhibited by a participant during intervention classes or study visits that 
endangers the safety or comfort of other study participants, class instructors, or study staff; 
or 3) decision to terminate the study by the IRB, NIDDK, or other regulatory bodies. 
Participants may also decide that they want to discontinue participation in interventions, 
even if study staff urge them to complete assigned 12-week intervention programs. 
In the event that participation in yoga or control intervention programs is discontinued, but 
the principal investigator and the participant feel it is safe, feasible, and appropriate for the 
participant to continue to provide outcomes data, the participant will continue to be followed 
through 36 weeks (until the original expected 24-week post-intervention assessment) to 
collect outcomes data. If follow-up assessments are continued, no modifications to the 
schedule of follow-up assessments will be made unless necessary to protect the safety of 
participants or to accommodate limitations in function resulting from an adverse event.  
Follow-up assessments in participants who have discontinued the therapeutic interventions 
will not include continued evaluation of adherence to group classes or home practice, 
assessment of yoga posture or practice adherence self-efficacy, or independent evaluation 
of participants’ success in performing yoga postures or stretching/strengthening exercises. 
9. STATISTICAL CONSIDERATIONS  
9.1 
General Design Issues  
A randomized, parallel-group, superiority trial design has been selected as the being 
the most appropriate design for the scientific goals of this research. Eligible 
participants will be randomly assigned in equal ratios to the yoga versus control 
interventions, with equivalent time and attention spent on study intervention and 
assessment procedures in both groups. 
A non-specific muscle stretching-strengthening exercise program has been selected 
as an active behavioral control intervention for this trial. Although this control 

 
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intervention may offer non-specific benefits for participants’ health, the investigators 
believe that it is unlikely to improve incontinence symptoms to the same extent as 
the yoga intervention. Inclusion of this plausible control intervention will also 
minimize differential expectations of treatment benefit between participants in the two 
groups, thus promoting similar adherence to interventions and visits in both groups. 
9.2 
Sample Size  
Sample size has been calculated based on parameter estimates derived from both 
the investigators’ past pilot studies on yoga as well as other group-based 
incontinence intervention trials conducted by study team members.103 Assumptions 
include: a) average baseline frequency of incontinence of ~23-24 episodes/week; b) 
standard deviation (SD) of change in incontinence frequency of ~14.4; c) correlation 
between outcome values of ~0.59; and d) loss of ~15% by 3 months. Assuming a 
~50% decrease in incontinence frequency among controls (which is the threshold at 
which women with daily incontinence start to perceive meaningful benefit from 
treatment18), the team will power the study to detect a between-group difference in 
reduction in incontinence of at least 20% in the yoga versus stretching/strengthening 
control group (corresponding to a ≥70% reduction in frequency of incontinence in the 
yoga group) at 3 months. Under these assumptions, a sample size of 240 (120 per 
group) will provide 80% power in 2-sided tests with 5% type-I error to detect a 
between-group difference in reduction in the primary outcome of total incontinence 
frequency of at least 20% in the yoga vs. control arm. With regard to secondary 
outcomes, this sample will also provide 80% power to detect moderate between-
group differences of 0.26 to 0.39 SDs, assuming intraclass correlation of outcomes in 
the range of 0.4-0.8. 
9.3       Randomization and Blinding 
Randomization to the yoga or control intervention group will be performed by 
computer algorithm, with proof of eligibility required before assignment.  
Randomization will be implemented using randomly permuted blocks of sizes 2 and 
4, and will also be stratified by clinical type of incontinence (i.e., stress-predominant, 
urgency-predominant), to ensure adequacy of randomization within types. To avoid 
manipulation, standard allocation concealment procedures will be followed.102  An 
analyst will prepare sealed, opaque envelopes containing group assignment, 
numbered consecutively with the randomization sequence numbers.  At the baseline 
visit, when eligibility and incontinence type have been confirmed, coordinators will 
enter the date, participant name, and study ID in the randomization log and select 
the next numbered envelope to determine group assignment. All envelopes will be 
retained for review; randomization dates and times should follow the order of the 
sequence numbers, providing a check on validity.   
Due to the behavioral nature of the intervention, participants cannot be blinded to 
intervention assignment, nor can study staff responsible for administering 
interventions or monitoring adherence to interventions. However, study investigators 
and staff members who are not involved in administering interventions or monitoring 
adherence to interventions will be blinded.  
Diary data used to evaluate primary and secondary efficacy outcomes will be 
abstracted by blinded analysts. Study-wide unblinding for the 12-week intervention 
period will take place when data from all dataforms and study measurements for the 
12-week intervention period have been entered into the database for all participants, 

 
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data cleaning for this period has been completed, and the principal investigator has 
declared the 12-week study dataset to be complete. Unblinding of study investigators 
or staff prior to the study-wide unblinding date will be undertaken only in exceptional 
circumstances in which knowledge of intervention assignment is essential to guide 
treatment or to protect the safety of a participant. 
9.4     Interim Analyses and Stopping Guidelines 
Interim analyses and/or stopping for unexpected efficacy: Since the trial involves low-
risk behavioral interventions that are of limited duration, the investigators believe that 
there is no scientific or ethical reason to stop the trial early or alter the trial design if 
treatment appears to be more effective than expected. Thus, as long as no safety 
issues arise, the trial will not be stopped or altered if the therapeutic intervention 
appears unexpectedly effective.  
Interim analyses and/or stopping for harm: Although this study involves low-impact 
behavioral interventions that are not expected to pose a significant risk to participant 
safety, consideration may be given to stopping the trial early if unexpected and 
clinically significant adverse effects occur in either intervention group that may 
endanger the safety of participants. These may take the form of SAEs or non-serious 
AEs posing a substantial safety risk and warranting early termination of the trial. If 
evidence of adverse effects emerges, the investigators in consultation with the DSM 
may determine that these side effects are minor and the study can continue as 
planned, or may decide to alter or stop the study to prevent these side effects.  
Interim analyses and stopping for futility: Consideration may be given to stopping the 
trial if recruitment and retention are so poor that the ability to meet recruitment goals 
or meet retention thresholds is severely compromised. For example, consideration 
will be given to stopping this study prior to its scheduled completion if recruitment 
falls more than 30% below planned rates and/or timely follow-up (i.e., completion of 
study visits within recommended windows) falls below 70%. 
9.5 
Outcomes  
9.5.1 Primary Efficacy Outcome   
The primary efficacy outcome will be change in the average frequency of any 
urinary incontinence over 12 weeks based on a validated 3-day voiding diary.  
To that end, frequency of incontinence will be assessed based on voiding 
diaries completed at screening/baseline, 6 weeks, and 12 weeks. If 
improvement in incontinence is observed over 12 weeks, additional analyses 
may explore persistence of benefits 12 and 24 weeks after the completion of 
the yoga or stretching/strengthening programs.   
9.5.2 Secondary Efficacy Outcomes   
Secondary efficacy outcomes will include change in the frequency of stress-
type, urgency-type, daytime, and nighttime incontinence, also assessed using 
validated voiding diaries, over 12 weeks. The total number of any, stress-
type, and urgency-type incontinence episodes will be calculated for each 
diary and then divided by the total number of days of recording to calculate 
the average number of incontinence episodes per day of each type.   
Other secondary efficacy outcomes will include change in quality-of-life 
outcomes associated with incontinence over 12 weeks.  To that end, changes 

 
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in depression and anxiety symptoms and incontinence-related quality of life 
will be assessed using validated questionnaires completed at 
screening/baseline, 6 weeks, and 12 weeks, as well as 12 and 24 weeks after 
the completion of yoga or control programs. 
9.6 
Data Analyses  
9.6.1    Analyses to address main objectives 
Objective 1: To determine the efficacy of a group-based yoga intervention in 
reducing the frequency of urinary incontinence in ambulatory midlife and older 
women.  
Hypothesis 1A: Ambulatory incontinent women randomized to the yoga intervention 
will demonstrate at least a 20% greater decrease in total incontinence frequency 
(measured by validated voiding diaries) over 12 weeks, compared to women 
randomized to the control intervention.  
Hypothesis 1B: If improvements in total incontinence frequency are observed at 12 
weeks, these improvements will be sustained 12 and 24 weeks after the end of the 
intervention programs. 
Planned analyses: Intervention effects on the primary outcome of total incontinence 
frequency will be estimated using a linear mixed model (LMM) for changes since 
baseline in the overall frequency of any incontinence episodes at 6 and 12 weeks, 
adjusting for baseline incontinence frequency. Analyses will be by intention to treat, 
according to intervention group assignment, and without regard to adherence to 
intervention classes or practice. The LMM will account for clustering using nested 
random effects for group intervention class series and individual participant. In 
addition to fixed effects for study location and type of incontinence, the LMM will 
include terms for intervention, time, and the time-by-intervention interaction, thus 
allowing for secular trends in controls, as well as different intervention effects at 6 
and 12 weeks. The intervention effect will be summarized by an orthogonal contrast 
capturing any linear trend across 6 and 12 weeks; this makes use of information for 
participants with 6 but not 12 week outcomes. If the yoga intervention appears 
effective over 12 weeks, we will also assess maintenance of effects over time, by 
comparing changes since baseline at 12 weeks with those at 24 and 36 weeks, using 
an additional LMM.  Intervention effects will again be summarized by an orthogonal 
contrast for linear trend across the three time points.   
 
Objective 2: To determine the efficacy of a group-based yoga intervention in 
reducing the frequency of type- and context-specific urinary incontinence in 
ambulatory middle-aged and older women.  
Hypothesis 2A: Ambulatory incontinent women randomized to the yoga intervention 
will report decreases in the frequency of stress-type, urgency-type, daytime, and 
nighttime incontinence (also measured by voiding diaries) over 12 weeks, compared 
to women randomized to the control intervention.  
Hypothesis 2B: If improvements in stress-type, urgency-type, daytime, and nightime 
incontinence frequency are observed at 12 weeks, these improvements will be 
sustained 12 and 24 weeks after the end of the intervention programs. 
Planned analyses: For additional confirmation of effects on the primary outcome of 
total incontinence frequency, we will examine effects on frequency of urgency 

 
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incontinence episodes and stress incontinence episodes, again using the modeling 
approach indicated above. Additional models will explore effects on frequency of 
daytime and nighttime incontinence.  
 
Objective 3: To determine the efficacy of the yoga intervention in improving 
incontinence-related functioning and quality-of-life.  
Hypothesis 3A: Ambulatory incontinent women randomized to the yoga intervention 
will report greater improvements in condition-specific functioning and quality of life 
(assessed by validated questionnaires) over 12 weeks, compared to women 
randomized to the control intervention.  
Hypothesis 3B: Compared to women randomized to the control intervention, we 
hypothesize that women randomized to the yoga intervention will report sustained 
improvements in condition-specific quality of life 12 and 24 weeks after the end of the 
intervention programs. 
Planned analyses: Additional LMMs will examine other secondary outcomes 
including incontinence-related quality of life as assessed by validated questionnaires 
(i.e., the Incontinence Impact Questionnaire (IIQ), Urogenital Distress Inventory 
(UDI), Patient Perception of Bladder Condition (PPBC), Pelvic Organ 
Prolapse/Incontinence Sexual Questionnaire, and IUGA-Revised (PISQ-IR) 
questionnaire), as well as depression and anxiety symptoms assessed by additional 
questionnaires (i.e., the Center for Epidemiology Studies Depression Scale (CES-D), 
Hospital and Anxiety Depression Scale (HADS), and State Trait Anxiety Inventory 
(STAI).  We will again estimate intention-to-treat intervention effects, adjusting for 
study location, using the same modeling strategy as for objective 1. Transformation 
or categorization of questionnaire scores (in combination with logistic or proportional 
odds models) will be considered as needed to deal with skewness of outcomes.     
Objective 4:  To explore whether the yoga intervention is associated with 
improvements in 1) pelvic floor muscle strength, 2) peripheral autonomic function, 
and/or 3) lower extremity physical function, and assess whether improvements in 
these factors may mediate improvement in incontinence.  
Hypothesis 4A: Among ambulatory incontinent women enrolled in this trial, the yoga 
intervention will be associated with improvements in a) pelvic floor muscle strength 
(assessed by pelvic exam), b) cardiac autonomic function (assessed by heart rate 
variability and impedance cardiography), and c) lower extremity physical function 
(assessed by physical performance assessment) over 12 weeks. 
Hypothesis 4B: Among ambulatory incontinent women enrolled in this trial, changes 
in incontinence frequency over 12 weeks will be partly mediated by changes in a) 
pelvic floor muscle strength, b) cardiac autonomic function, and c) lower extremity 
physical function. 
Planned analyses: Additional intermediary outcomes include pelvic floor muscle 
strength (measured by Brink scale), peripheral autonomic function (reflected by 
respiratory sinus arrhythmia [RSA] and cardiac pre-ejection period [PEP] 
parameters), and lower extremity physical function (assessed using the Short 
Physical Performance Battery [SBBP] and 2-minute step test). Intervention effects 
will first be estimated using LMMs, using the same modeling strategy used for 
objectives 1-3. Next, to assess for mediation of changes in incontinence frequency 
by changes in these factors, we will assess correlation between changes in these 

 
43 of 54 
 
 
 
parameters and change in incontinence frequency between baseline and 12 weeks. 
We will then examine attenuation of intervention effects estimates from the primary 
intention-to-treat analyses after adjustment for these potential mediators. Mediators 
will initially be analyzed as continuous variables (i.e., continuous change in RSA and 
PEP), but categorization will be considered in the event of skewed variable 
distributions. If evidence of mediation is observed, we will estimate 95% bias-
corrected percentile confidence intervals confidence intervals for the proportion of 
intervention effect explained, using resampling by participant to fully account for the 
correlation between intervention effect estimates before and after adjustment for 
change in the mediators 
 
9.6.2    Other analytic issues 
Participant dropout (i.e., early termination or loss-to-follow-up).  Participant dropout 
levels are expected to be <15% at 12 weeks of intervention, <20% at 12 weeks post-
intervention follow-up, and <25% at 24 weeks post-intervention follow-up, assuming 
a similar rate of attrition over time. The assumption of non-informative dropout will be 
assessed by comparing baseline characteristics and early post-randomization 
outcomes of dropouts vs. non-dropouts.  If dropout rates differ between groups, 
sensitivity analyses to evaluate the effects of participant dropout on estimates of 
intervention effects may be run using inverse probability of retention weights, which 
can legitimately include post-randomization variables associated with dropout. 
Alternately or in addition to this, we may use multiple imputation of missing outcomes 
under plausible informative missingness assumptions.104 
Dose effects (length of exposure and intensity of practice). In the event that the 
primary analysis shows that yoga intervention is effective in reducing incontinence 
frequency over 12 weeks, we may use a closed test procedure to assess for dose 
response in length of intervention exposure without inflating type-I error.105 
Specifically, if we detect a statistically significant benefit over 12 weeks an alpha of 
0.05, we may assess change from baseline to 6 weeks, and from 6 weeks to 12 
weeks, also at alpha of 0.05, based on contrasts that can be obtained from the 
primary analysis model. In exploratory analyses, we may also examine whether 
cumulative hours spent in group intervention classes (based on class attendance 
logs), or total hours of home yoga or stretching/strengthening practice (documented 
by participants’ home practice logs), are associated with changes in incontinence 
frequency or secondary outcomes in each group.  After the end of the 12-week 
intervention, additional exploratory analyses may examine associations between 
continued yoga or control intervention practice (based on continued home practice 
hours) and maintenance of intervention effects. 
 
Exploratory subgroup analyses.  Intervention effects will be analyzed in subgroups in 
multivariate analysis based on a limited set of clinicopathologic factors that are 
hypothesized to have the potential to influence participants’ response to the yoga 
and stretching/strengthening interventions. For example, we may explore whether 
baseline participant age, race/ethnicity, clinical type of incontinence, pelvic floor 
muscle strength, or physical function levels influence subsequent treatment-
associated changes in primary and secondary outcomes. Subgroup-specific effects, 
estimated using the interaction model, will be presented only if the interaction 
between treatment and subgroup is statistically significant at p<0.05. 
 

 
44 of 54 
 
 
 
During the COVID-19 pandemic, intervention instruction in some study waves may 
be converted to remote platforms (i.e., interactive video-based class instruction 
rather than in-person class instruction). In that event, we will use the methods 
outlined above for exploratory subgroup analyses to evaluate differences in the effect 
of the intervention in waves that rely primarily on video-based instruction rather than 
in-person instruction. 
   
Co-intervention effects. Because awareness of intervention assignment can affect 
use of co-interventions, women in both groups will be asked to refrain from using 
other clinical incontinence treatments during the study. Nevertheless, information 
about co-interventions will be collected at follow-up visits to permit assessment of 
potential effects of differential use of co-interventions on outcomes.  To estimate the 
direct effect of the intervention in the absence of co-interventions, we may conduct 
additional analyses to add co-intervention use, as well as confounders of its effect on 
the outcome, to the primary treatment model; if factors that are also affected by the 
co-interventions are among the confounders, we may use inverse weighting rather 
than direct adjustment for this purpose. 
10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1 
Data Collection Forms  
Study data will be obtained from participant-completed symptom diaries and logs, 
participant- or interviewer-administered questionnaires, physical examination and 
performance measures, and urine sampling/testing. Forms for recording or 
abstracting data will be developed specifically for this study, including: 
- 
Voiding diary abstraction form: After participants complete their voiding diary at 
home, they will return the completed diary to the study clinic, and diary data will 
be abstracted using a Voiding Diary Abstraction Form. At the Baseline Visit, a 
clinical coordinator will abstract diary data for eligibility assessment purposes; at 
all post-randomization follow-up assessments, an analyst who is blinded to 
intervention assignment will abstract diary data. 
- 
Questionnaires assessing depression and anxiety, condition-specific quality of 
life, and participant satisfaction:  These questionnaire forms will be completed by 
the participant during clinic visits and returned in person to a clinical coordinator, 
or completed by the participant at home and then mailed back to the study clinic. 
Participants may enter questionnaire responses directly into the electronic study 
database using computer tablets or electronic questionnaire links. If 
questionnaires assessing study efficacy outcomes are completed by participants 
on paper after randomization and then entered by study staff, then the staff 
member responsible for data entry will be blinded to intervention assignment. 
- 
Questionnaires assessing demographic history, general medical and 
urologic/urogynecologic history, medication use, tobacco and alcohol use, and 
physical activity and function: These questionnaires will be administered by a 
clinical coordinator during in-person study visits, and data from questionnaires 
will be entered by the coordinator into the electronic database. Because these 
data will not be used to assess efficacy outcomes, coordinators who administer 
and entering data from these forms will not necessarily be blinded to intervention 
assignment. 

 
45 of 54 
 
 
 
- 
Physical examination and urine testing data forms: Clinical coordinators will 
record the results of height and weight measurements, blood pressure and heart 
rate measurements, and urine dipstick and pregnancy testing on study-specific 
forms, and data from these forms will then be entered by coordinators into the 
electronic database. Because these data will not be used to assess any efficacy 
outcomes, the coordinators who are responsible for collecting, recording, and 
entering these data will not necessarily be blinded to intervention assignment. 
10.2 
Data Management  
Data will be entered, managed, and edited using Medrio web-based Electronic Data 
Capture (EDC) software for Clinical Research, which is available for use without 
charge for investigator-initiated, university- or government-sponsored research. 
Medrio software meets the requirements for electronic records and signatures (21 
CFR Part 11) and HIPAA. Data entered via Medrio can be accessed from machines 
on any network, can accommodate multiple users, allows for users at different sites 
to be issued differed password-protected logins, and includes tools to allow users to 
load data that collected offline. 
10.3 
Quality Assurance  
10.3.1 Staff Training 
All investigators, project directors, and clinical coordinators involved in the 
study will complete training in Human Subjects Research, which in most 
cases will be training offered by the Collaborative Institutional Training 
Initiative (CITI). CITI Human Subjects Research training includes specific 
modules on assessing risk to subjects, avoiding group harms, conflicts of 
interest, cultural competence, FDA-regulated research, HIPAA-regulated 
research, informed consent, IRB member responsibilities, IRB chair 
responsibilities, records-based research, research with vulnerable subjects, 
and unanticipated problems and reporting.  All investigators, project directors, 
and coordinators will maintain active CITI certification during the study. 
Coordinators and analysts involved in data collection will also attend a study-
specific training meeting led by the principal investigator and the project 
directors prior to the start of participant recruitment.  At a minimum, the 
training meeting will include: (1) an introduction to the goals, design, and 
procedures of the LILA study; (2) an overview of goals, structure, and 
procedures for administering and abstracting data from the voiding diary and 
other study-specific data collection measures; (3) a review of definitions and 
procedures for assessing, documenting, and reporting adverse events.   
Coordinators and analysts will also receive training and undergo supervised 
practice in reviewing and abstracting data from the voiding diary as the 
primary efficacy measure in the trial. They will also receive training and 
undergo supervised practice performing physical exam measures, assessing 
physical function/performance, and obtaining autonomic function 
measurements.  Following the training, clinical staff will be certified for 
performing these functions. 

 
46 of 54 
 
 
 
10.3.2 Data Quality Assessment 
Data collection forms will be reviewed on an ongoing basis for data 
completeness and accuracy as well as protocol compliance. Forms used to 
collect data on the primary efficacy outcome (i.e., voiding diary abstraction 
forms) will be verified against paper-based source forms by a staff member 
who was not originally involved in entering the data. 
 
Quality of data entry will be periodically assessed using measures such as 
number of missing diaries/forms and number of missing queries. The results 
of assessment of data quality will be incorporated into study progress reports 
for scheduled DSM meetings. 
10.3.3 Protocol Deviations 
Exceptions or deviations from the protocol are expected to occur rarely or not 
at all and, where possible, will be approved in advance by the principal 
investigator. Protocol exceptions/deviations may occur for the following 
reasons: 
• 
exceptions necessary to protect the safety or well-being of a participant 
(in this case, the protocol exception should apply to that participant only) 
• 
deviations due to oversight or error on the part of study staff, and 
subsequently detected by the investigators or study personnel. 
 
For each protocol exception/deviation, study staff will document the event on 
a Protocol Deviations Log (located in the Regulatory Binder). Entries in the 
Protocol Deviations Log should include the participant ID, date of the 
deviation, the date the deviation is recorded, description of the deviation, and 
action taken in response to the deviation, if any. The principal investigator will 
document approval for each deviation determined in advance, or 
acknowledgement for each deviation detected after the fact.  
 
For this study, missed yoga or control intervention classes will not be 
considered a protocol deviation, and neither will failure to complete 
recommended home practice sessions, although study staff will make every 
effort to promote adherence to classes and home practice (see adherence 
section above). 
10.3.4 External Monitoring 
If desired by NIDDK, the study team will undergo on-site monitoring by an 
independent quality monitor who is independent of both the sponsor and 
UCSF. Site monitoring visits may include review of participant records, 
informed consent forms, source dataforms, and the electronic study 
database. The schedule of site monitoring will be agreed upon in advance by 
the NIDDK, the principal investigator, and the independent monitoring 
organization. The principal investigator, project manager, and study 
coordinators will be available to meet in person with the external monitor and 
provide access to study-specific forms, materials, and databases. 

 
47 of 54 
 
 
 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
11.1 
Institutional Review Board (IRB) Review  
The study protocol, informed consent document, data and safety monitoring plan, 
and data collection forms will be reviewed and approved by the UCSF IRB prior to 
implementation of study procedures. Any subsequent modifications to these 
documents will also be reviewed and approved by the UCSF IRB prior to 
administration in the study. 
11.2 
Informed Consent Forms 
A signed consent form will be obtained from each participant at the Screening Visit 
before in-person data collection procedures are initiated (see section on informed 
consent procedures). A copy of the consent form will be given to each participant, 
and documentation of signed consent will be filed in the participant’s study file. 
11.3 
Participant Confidentiality  
Study data will be protected to preserve participant confidentiality both during and 
after the study. Each participant will be assigned a unique numerical study identifier 
which will be used on study forms instead of names or other identifying information. 
Only the study coordinators or investigators who need to get access to identifiers in 
order to contact participants will have access to the document linking study IDs to 
participant identifiers. Any paper source forms will be stored in locked cabinets in 
locked study offices, and only research personnel who need to access these forms 
for data collection, editing, or safety/quality monitoring will have access to them. 
Information that could identify individual participants will not be released without 
written permission of the participant, except as necessary for monitoring by the IRB, 
NIDDK, OHRP, or other agencies responsible for protecting participant safety. 
11.4 
Study Discontinuation  
The study may be discontinued by the Steering Committee at any time at the 
recommendation of the UCSF IRB, the NIDDK, the OHRP, or other government 
agencies if necessary to protect the safety or confidentiality of research participants.  
12.  ETHICAL CONSIDERATIONS 
This research will be conducted in accordance with principles outlined in, "The Belmont 
Report: Ethical Principles and Guidelines for the Protection of Human Subjects in 
Research" (National Commission for the Protection of Human Subjects of Biomedical and 
Behavioral Research, April 1979), which include respect for persons, beneficence, and 
justice. 
13.  STEERING/PUBLICATIONS COMMITTEE 
Conduct of this research will be overseen by a Steering Committee composed of the 
principal investigator Alison Huang, MD, MAS and co-investigators Leslee Subak, MD and 
Margaret Chesney, PhD. Publication of the results of this trial will be governed by the 
policies and procedures developed by the Steering Committee. 

 
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14.  PUBLICATION OF RESEARCH FINDINGS  
Any publications resulting from this research will be made available to the public, in 
accordance with NIH public access policy. At the request of the NIDDK program officer, the 
principal investigator will also provide a copy of any abstracts or manuscripts resulting from 
this work to the program officer prior to submission. 
15. REFERENCES  
1. 
Melville JL, Katon W, Delaney K, Newton K. Urinary incontinence in US women: a 
population-based study. Arch Intern Med. 2005;165(5):537-542. 
2. 
Thom DH, Haan MN, Van Den Eeden SK. Medically recognized urinary incontinence 
and risks of hospitalization, nursing home admission and mortality. Age Ageing. 
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