Randomized Controlled Trial of Mindfulness-based Stress Reduction Plus Prenatal Sleep Supplement Versus Usual Care: Acceptability, Feasibility, and Adherence
Phase: NA
Conditions: Sleep, Pregnancy Related
Sponsor: University of California, San Francisco

 
 
 
Randomized controlled trial of mindfulness-
based stress reduction plus prenatal sleep 
supplement versus usual care: Acceptability, 
feasibility, and adherence 
Protocol Number: Not applicable; this is the first version of the protocol 
National Clinical Trial (NCT) Identified Number:  NCT05017974 
Principal Investigator: Jennifer Felder, PhD 
Sponsor: University of California, San Francisco 
Grant Title: Optimizing a mindfulness-based intervention for poor sleep 
quality during pregnancy 
Grant Number: K23AT009896 
Funded by: National Center for Complementary and Integrative Health 
Version Number:  v.3 
November 8, 2021 
 
 

 
 
Specific Changes Implemented in Current Version 
 
Description of Change  
Brief Rationale 
1. Include MBSR 
classes that are 
offered at locations in 
addition to UCSF 
Osher Center 
 
1. A significant challenge is that the UCSF Osher Center 
does not offer MBSR frequently, and the classes fill up 
quickly. Currently, the number of eligible RISE Study 
participants exceeds the available spots in the Osher 
MBSR class. Additionally, we have had otherwise 
eligible study participants who were unable to 
participate because they were not available at the 
particular time of the Osher MBSR class 
2. Add recruitment 
sources 
2. To enable rapid identification of eligible participants 
and to maximize likelihood that we can achieve our 
anticipated accrual rate. We are having a lower yield 
from our Facebook ads compared to our previous 
studies. We are adding recruitment sources that we 
found helpful in previous studies, such as parenting 
listservs and social media posts 
3. Remove Epworth 
Sleepiness Scale 
3. Initially we planned to use the Epworth to screen for 
narcolepsy. The Epworth has excluded 10% of 
respondents on our screener. Narcolepsy has a base 
rate of 0.05%. Thus, it is highly implausible that 10% 
of respondents had narcolepsy. Instead we believe the 
Epworth is identifying people with normative 
pregnancy-related sleepiness. Additionally, this 
measure is redundant with an item that assesses 
whether participants have been diagnosed with 
narcolepsy 
4. Increase the 
gestational age range 
from 12-28 to 8-28. 
4. We have had several potential participants who are 
experiencing significant sleep disruption, are 
interested in participating, but are less than 12 weeks 
pregnant (and will be too far along in their pregnancy 
for the next available MBSR course). This wider 
gestational age range is similar to our previous 
research, in which we evaluated digital CBT for 
prenatal insomnia, and enrolled participants at any 
point in pregnancy up until 28 weeks 
 
 
 

 
 
STUDY TEAM ROSTER 
Name 
Role 
Email 
Phone 
Address 
Jennifer Felder, 
PhD 
Principal 
investigator 
Jennifer.Felder@ 
ucsf.edu 
415-
476-
7014 
3333 California 
Street, San 
Francisco, CA 
94143 
Elissa Epel, 
PhD 
Co-
investigator; 
K23 Mentor 
Elissa.Epel@ 
ucsf.edu 
415-
476-
7648 
3333 California 
Street, San 
Francisco, CA 
94143 
Andrew Krystal, 
MD 
Co-
investigator; 
K23 Mentor 
Andrew.Krystal@ 
ucsf.edu 
415-
476-
7702 
401 Parnassus 
Avenue, San 
Francisco, CA 
94143 
Frederick 
Hecht, MD 
Co-
investigator; 
K23 Mentor 
Rick.Hecht@ 
ucsf.edu 
415-
476-
4082 
1545 Divisadero 
Street, San 
Francisco, CA 
94143 
Patricia Moran, 
PhD 
Project 
manager 
Patricia.Moran@ 
ucsf.edu 
 
415-
353-
9745 
1545 Divisadero 
San Francisco 
CA 94115 
Riya 
Mirchandaney, 
BA 
Clinical 
research 
coordinator 
Riya.Mirchandaney 
@ucsf.edu 
 
267-
344-
5069 
3333 California 
Street, San 
Francisco, CA 
94143 
Natalie 
Solomon, PsyD 
Prenatal sleep 
content 
instructor 
nsolo@ stanford.edu 
 
401 Quarry 
Road, Stanford, 
CA 94305 
Judith Cuneo, 
MD 
K23 
Specialized 
advisor 
Judith.Cuneo@ 
ucsf.edu 
415-
885-
7788 
1545 Divisadero 
Street, San 
Francisco, CA 
94143 
Rachel Manber, 
PhD 
K23 
Specialized 
advisor 
Rmanber@ 
stanford.edu 
650-
498-
9111 
401 Quarry 
Road, Stanford, 
CA 94305 

 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by 
the recipient that no unpublished information contained herein will be published or disclosed without 
prior approval of the Principal Investigator or other participating study leadership and as consistent with 
the NIH terms of award.  
 

Randomized controlled trial of a mindfulness-based intervention for prenatal sleep  
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Table of Contents 
STATEMENT OF COMPLIANCE ................................................................................................................. 1 
INVESTIGATOR’S SIGNATURE ................................................................................................................. 2 
1 
PROTOCOL SUMMARY ................................................................................................................... 3 
1.1 
Synopsis .................................................................................................................................. 3 
1.2 
Schema ................................................................................................................................... 4 
1.3 
Schedule of Activities .............................................................................................................. 5 
2 
INTRODUCTION ............................................................................................................................... 6 
2.1 
Study Rationale ....................................................................................................................... 6 
2.2 
Background ............................................................................................................................. 6 
2.3 
Risk/Benefit Assessment ......................................................................................................... 8 
2.3.1 
Known Potential Risks .................................................................................................... 8 
2.3.2 
Known Potential Benefits ............................................................................................... 9 
2.3.3 
Assessment of Potential Risks and Benefits ............................................................... 9 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................... 11 
4 
STUDY DESIGN ............................................................................................................................. 14 
4.1 
Overall Design ....................................................................................................................... 14 
4.2 
Scientific Rationale for Study Design .................................................................................... 15 
4.3 
Justification for Intervention ................................................................................................... 15 
4.4 
End-of-Study Definition ......................................................................................................... 16 
5 
STUDY POPULATION .................................................................................................................... 16 
5.1 
Inclusion Criteria .................................................................................................................... 16 
5.2 
Exclusion Criteria .................................................................................................................. 17 
5.3 
Lifestyle Considerations ........................................................................................................ 17 
5.4 
Screen Failures ..................................................................................................................... 17 
5.5 
Strategies for Recruitment and Retention ............................................................................. 17 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ....................................... 20 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration .................................. 20 
6.1.1 
Study Intervention or Experimental Manipulation Description ................................ 20 
6.1.2 
Administration and/or Dosing ...................................................................................... 20 
6.2 
Fidelity ................................................................................................................................... 21 
6.2.1 
Interventionist Training and Tracking ......................................................................... 21 
6.3 
Measures to Minimize Bias: Randomization and Blinding ..................................................... 21 
6.4 
Study Intervention/Experimental Manipulation Adherence .................................................... 22 
6.5 
Concomitant Therapy ............................................................................................................ 22 
6.5.1 
Rescue Therapy ............................................................................................................ 22 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ................................................................................ 22 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ........................................ 22 
7.2 
Participant Discontinuation/Withdrawal from the Study ......................................................... 23 
7.3 
Lost to Follow-Up .................................................................................................................. 23 
8 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................. 23 
8.1 
Endpoint and Other Non-Safety Assessments ...................................................................... 23 
8.2 
Safety Assessments .............................................................................................................. 26 
8.3 
Adverse Events and Serious Adverse Events ....................................................................... 27 
8.3.1 
Definition of Adverse Events ........................................................................................ 27 
8.3.2 
Definition of Serious Adverse Events ......................................................................... 27 
8.3.3 
Classification of an Adverse Event ............................................................................. 27 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ...................... 29 

Randomized controlled trial of a mindfulness-based intervention for prenatal sleep  
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8.3.5 
Adverse Event Reporting ............................................................................................. 29 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 30 
8.3.7 
Reporting Events to Participants ................................................................................. 30 
8.3.8 
Events of Special Interest ............................................................................................ 30 
8.3.9 
Reporting of Pregnancy ................................................................................................ 30 
8.4 
Unanticipated Problems ........................................................................................................ 30 
8.4.1 
Definition of Unanticipated Problems ......................................................................... 30 
8.4.2 
Unanticipated Problems Reporting ............................................................................. 31 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 31 
9 
STATISTICAL CONSIDERATIONS ................................................................................................ 31 
9.1 
Statistical Hypotheses ........................................................................................................... 31 
9.2 
Sample Size Determination ................................................................................................... 32 
9.3 
Populations for Analyses ....................................................................................................... 32 
9.4 
Statistical Analyses ............................................................................................................... 32 
9.4.1 
General Approach ......................................................................................................... 32 
9.4.2 
Analysis of the Primary Endpoint(s) ........................................................................... 32 
9.4.3 
Analysis of the Secondary Endpoint(s) ...................................................................... 32 
9.4.4 
Safety Analyses ............................................................................................................. 33 
9.4.5 
Baseline Descriptive Statistics .................................................................................... 33 
9.4.6 
Planned Interim Analyses ............................................................................................ 33 
9.4.7 
Sub-Group Analyses ..................................................................................................... 33 
9.4.8 
Tabulation of Individual Participant Data ................................................................... 33 
9.4.9 
Exploratory Analyses .................................................................................................... 34 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ........................... 34 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ..................................................... 34 
10.1.1 
Informed Consent Process .......................................................................................... 34 
10.1.2 
Study Discontinuation and Closure ............................................................................. 34 
10.1.3 
Confidentiality and Privacy ........................................................................................... 35 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 36 
10.1.5 
Key Roles and Study Governance .............................................................................. 37 
10.1.6 
Safety Oversight ............................................................................................................ 37 
10.1.7 
Clinical Monitoring ......................................................................................................... 38 
10.1.8 
Quality Assurance and Quality Control ...................................................................... 38 
10.1.9 
Data Handling and Record Keeping ........................................................................... 38 
10.1.10 
Protocol Deviations ....................................................................................................... 39 
10.1.11 
Publication and Data Sharing Policy .......................................................................... 39 
10.1.12 
Conflict of Interest Policy .............................................................................................. 40 
10.2 
Additional Considerations ...................................................................................................... 40 
10.3 
Abbreviations and Special Terms .......................................................................................... 40 
10.4 
Protocol Amendment History ................................................................................................. 42 
11 
REFERENCES ............................................................................................................................... 44 
 

Randomized controlled trial of a mindfulness-based intervention for prenatal sleep  
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STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with International Council on Harmonisation 
Good Clinical Practice (ICH GCP), applicable United States (US) Code of Federal 
Regulations (CFR), and the National Center for Complementary and Integrative Health 
(NCCIH) Terms and Conditions of Award. The Principal Investigator will assure that no 
deviation from, or changes to the protocol will take place without prior agreement from 
the funding agency and documented approval from the Institutional Review Board (IRB), 
except where necessary to eliminate an immediate hazard(s) to the trial participants. All 
personnel involved in the conduct of this study have completed Human Subjects 
Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant 
materials will be submitted to the IRB for review and approval. Approval of both the 
protocol and the consent form(s) must be obtained before any participant is consented. 
Any amendment to the protocol will require review and approval by the IRB before the 
changes are implemented to the study. All changes to the consent form(s) will be IRB 
approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent 
form. 
 
 

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INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the 
necessary assurances that this study will be conducted according to all stipulations of 
the protocol, including all statements regarding confidentiality, and according to local 
legal and regulatory requirements and applicable US federal regulations and ICH 
guidelines, as described in the Statement of Compliance above. 
 
Principal Investigator: 
Signed: 
 
Date:  
 
Name: Jennifer Felder, PhD 
 
Title: Assistant Professor 
 
Investigator Contact Information 
Affiliation: University of California, San Francisco 
Telephone: (415) 476-7014 
Email: Jennifer.felder@ucsf.edu 
 
 
 
 
 
 

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1 
PROTOCOL SUMMARY 
1.1 SYNOPSIS  
 
Title: 
Randomized controlled trial of mindfulness-based stress 
reduction plus prenatal sleep supplement versus usual 
care: Acceptability, feasibility, and adherence 
Grant Number: 
K23AT009896 
Study Description: 
The goal of this trial is to conduct a pilot randomized 
controlled trial to evaluate mindfulness-based stress 
reduction plus prenatal sleep supplement to improve 
prenatal sleep (MBSR + PS) compared to treatment as 
usual (TAU). Our primary focus is on evaluating 
acceptability, feasibility, and adherence. Secondarily, 
we will explore condition differences in hypothesized 
targets (i.e., psychological responses to nightly physical 
symptoms) and the clinical outcome of interest (i.e., 
subjective sleep quality). 
Objectives: 
 
Primary Objectives: Acceptability, feasibility, adherence 
Secondary Objectives: Change in psychological 
responses to nightly physical symptoms; between group 
differences in global sleep quality 
Endpoints: 
Primary Endpoint: Willingness to be randomized, 
treatment initiation, reasons for attrition, satisfaction; 
Yield of eligible participants, number randomized, 
retention rate, completeness, missingness; Session 
attendance, home practice completion 
Secondary Endpoints: 14-day daily diary, validated 
retrospective measures of psychological constructs 
hypothesized as mediators; subjective sleep quality 
Study Population: 
50 women 12-28 weeks gestation with poor sleep 
quality 
Phase: 
Stage 1B in the NIH Stage Model for behavioral 
intervention development  
Description of Site 
Enrolling Participants: 
Single site study at University of California, San 
Francisco.   
Description of Study 
Intervention: 
The study intervention is standard mindfulness-based 
stress reduction (MBSR). The supplemental prenatal 
sleep content draws material from mindfulness-based 
therapy for insomnia, mindfulness-based childbirth and 
parenting program, and cognitive behavior therapy for 
prenatal insomnia.   
Study Duration: 
12 months 
Participant Duration: 
Approximately 3 months 

Randomized controlled trial of a mindfulness-based intervention for prenatal sleep  
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1.2 SCHEMA  
Flow Diagram  
 
 
 
 
 
 
 
 
 
 

Randomized controlled trial of a mindfulness-based intervention for prenatal sleep  
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1.3 SCHEDULE OF ACTIVITIES  
 
 
 
Timepoint 
Screening 
Baseline 
Daily 
Weekly 
Endpoint 
Allowable window 
N/A 
0-4 weeks 
prior to 
randomization 
Within 
24 
hours 
Within 
3 days 
+/- 4 
weeks 
Screening consent 
x 
 
 
 
 
Screening measures 
x 
 
 
 
 
Demographic form 
x 
 
 
 
 
Orientation session 
x 
 
 
 
 
Study consent  
x 
 
 
 
 
14-day daily diary  
 
x 
 
 
x 
Outcome measures 
 
x 
 
 
x 
Depression measure 
 
 
 
x 
 
Home practice measure 
(MBSR+PS only) 
 
 
x 
 
 
Sleep diary (MBSR+PS only) 
 
 
x 
 
 
Use of non-study treatments 
questionnaire 
 
x 
 
 
x 
Adverse events questionnaire 
 
 
 
 
x 
Client Satisfaction 
Questionnaire 
 
 
 
 
x 

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2 
 
INTRODUCTION 
2.1 STUDY RATIONALE  
Poor sleep quality is highly prevalent during pregnancy,1 with important implications for 
maternal and infant health and well-being. That is, poor sleep is associated with 
increased risk of: depression;2,3 suicidal ideation;4 gestational diabetes;5 preterm birth;6,7 
and caesarean birth.8,9 Despite this, there is limited research on interventions to 
improve prenatal sleep, and prior research did not target the specific factors contributing 
to poor sleep quality in this population.  
Specifically, pregnant women report that physical symptoms, including discomfort and 
pain, disturb their sleep.1 In non-pregnant populations, the pain-sleep relationship is 
bidirectional,10 and maladaptive psychological responses to pain further exacerbate 
poor sleep.11,12 Although pregnancy-related discomfort and pain may be difficult to 
eliminate, psychological responses to such symptoms offer modifiable targets to break 
the pernicious discomfort/pain – poor sleep cycle.  
Theory and empirical evidence indicate that mindfulness-based interventions may be 
effective for targeting these psychological responses. For example, mindfulness-based 
stress reduction (MBSR) teaches skills to accept difficult, unchangeable experiences 
(like chronic pain13), and randomized controlled trials demonstrate improvements in 
sleep14 and responses to pain15-17 in non-pregnant populations. MBSR has been 
adapted to teach skills for coping with intense sensations during pregnancy and birth 
(mindfulness-based childbirth and parenting, MBCP)18 and to improve sleep among 
individuals with chronic insomnia (mindfulness-based therapy for insomnia, MBTI).14,19 
However, there is a paucity of research optimizing and evaluating mindfulness-based 
interventions for improving prenatal sleep quality.  
The goal of this trial is to conduct a pilot randomized controlled trial to compare a 
program consisting of MBSR plus prenatal sleep content (MBSR+PS) to treatment as 
usual (TAU). Our primary focus is on evaluating acceptability, feasibility, and 
adherence. Secondarily, we will explore condition differences in hypothesized targets 
(i.e., psychological responses to nightly physical symptoms) and the clinical outcome of 
interest (i.e., subjective sleep quality). 
2.2 BACKGROUND  
Poor sleep quality during pregnancy is common and associated with negative correlates 
and consequences for mom and baby. Over 75% of pregnant women report poor sleep 
quality, which is linked to adverse psychological and obstetric outcomes, such as 
increased risk of depression symptom severity,20 suicidal ideation after accounting for 
depression,4 gestational diabetes mellitus,5 preterm birth,6-8 and caesarean birth.8,9 
Moreover, prenatal poor sleep quality often persists into the postpartum period,20 
thereby maintaining and exacerbating postpartum depression.21 Thus, improving poor 
sleep quality during pregnancy may have significant health implications for both mother 
and offspring.  

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Pregnant women report that pregnancy-related physical symptoms, including 
discomfort, back pain, and hip/pelvic pain, disturb their sleep.1 Longitudinally, such 
symptoms predict worsening sleep quality.22 In non-pregnant populations, the pain-poor 
sleep association is bidirectional,10 and poor sleep exacerbates discomfort and pain.23,24 
It may be challenging to eliminate pregnancy-related discomfort and pain, but 
psychological responses are modifiable targets to break the pain/discomfort-poor sleep 
cycle. In studies of individuals with chronic pain, acceptance of pain predicted lower 
insomnia severity, after accounting for pain severity,11 and presleep rumination about 
pain was associated with longer sleep latency, after accounting for pain severity.12 Our 
preliminary data in a sample of 50 pregnant women indicated that physical symptoms 
were the most common reason women had trouble falling or staying asleep, relative to 
difficulties quieting the mind, other, or unknown. The psychological responses that had 
the strongest associations with sleep quality were: “I felt annoyed or bothered by my 
physical symptoms” (r = -0.29), “I reassured myself that my symptoms were normal” (r = 
0.17), and “I paid attention to my physical symptoms without trying to change them” (r = 
0.16). 
Current options for improving prenatal sleep are limited, but pregnant women want help. 
There is limited research on acceptable and effective interventions to improve sleep 
during pregnancy. Prescription medications, such as zolpidem, may be associated with 
increased risk of adverse birth outcomes25 and pregnant women prefer non-
pharmacological interventions for sleep.26 The small body of research examining non-
pharmacological interventions for improving sleep during pregnancy have used 
cognitive behavioral approaches to treat chronic insomnia. Such approaches target 
dysfunctional sleep beliefs and behaviors, but do not target the unique factors 
contributing to poor sleep quality during pregnancy. Previously, we found that 
significantly more pregnant women with insomnia who were randomized to digital 
cognitive behavior therapy for insomnia experienced remission in insomnia symptoms 
relative to women randomized to standard care;27 however, most women continued to 
experience at least subthreshold symptoms. Thus, targeting pregnancy-specific sleep 
disturbances, such as nocturia and discomfort, may help more women achieve 
symptom remission. Mindfulness-based and acceptance-based approaches that focus 
on increasing acceptance of physical symptoms that may be difficult to eliminate may 
be particularly well suited for pregnancy-related poor sleep. Taken together, these data 
emphasize the need for alternative approaches to improving prenatal poor sleep quality 
by addressing key mechanisms.  
Mindfulness-based intervention may be a promising approach for improving pregnancy-
related factors of poor sleep quality. Mindfulness-based stress reduction (MBSR) was 
developed to reduce psychological reactivity to chronic pain.28 In a group intervention, 
MBSR participants learn skills to notice and accept difficult, often unchangeable, 
sensations, emotions, and thoughts. Randomized clinical trials of MBSR among non-
pregnant populations demonstrate significant effects on the psychological mechanisms 
(pain acceptance15,16 and rumination17) that we hypothesize contribute to poor sleep 
quality during pregnancy, as well as on objective and subjective measures of sleep,14 
even in the context of chronic pain.29 Additionally, mindfulness-based therapy for 

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insomnia (MBTI) is effective for improving sleep among individuals with chronic 
insomnia.  
Nearly a quarter of pregnant women report using mind-body practices,30 and more 
pregnant women prefer mind-body intervention to pharmacotherapy for improving 
sleep.26 However, there is a paucity of research optimizing and evaluating a 
mindfulness-based intervention for improving sleep during pregnancy. The current trial 
seeks to address this critical gap. Improving sleep quality during pregnancy has the 
potential to avert its myriad negative consequences, with considerable implications for 
women and their families.  
2.3 RISK/BENEFIT ASSESSMENT  
2.3.1 KNOWN POTENTIAL RISKS  
MBSR+PS: Participation in the study intervention carries minimal risk of emotional 
discomfort. It is possible that participants may experience injury or discomfort during 
mindful stretching and walking practice; however, such practices may also improve pain 
during pregnancy.31 Previous studies of mindfulness-based interventions, including in 
pregnant populations, demonstrate safety and acceptability, with no adverse events 
reported. Some participants may be advised to implement techniques designed to 
consolidate sleep. These techniques reduce the amount of time spent awake in bed, 
which increases sleep drive, and ultimately decreases sleep onset latency and wake 
after sleep onset. Participants may experience temporary increases in sleepiness during 
this component of treatment. Two previous trials that included this technique among 
pregnant women found no unanticipated serious adverse events.27,32 We are aware of 
no research to suggest that the proposed intervention would confer risk to fetal, 
obstetric, or infant outcomes. At this time, there is a paucity of other treatments 
specifically for pregnancy-related poor sleep quality. Pharmacotherapy is associated 
with adverse birth outcomes,25 and pregnant women prefer non-pharmacological 
treatments.26 Cognitive behavior therapy targets maladaptive sleep beliefs and 
behaviors that are unique to chronic insomnia, and it does not address pregnancy-
related factors of poor sleep quality.  
Self-report questionnaires: There are no known risks for completing the study 
questionnaires, though it is possible that participants may experience temporary 
discomfort from thinking about their physical symptoms, psychological responses, and 
sleep.  
Actigraphy (optional depending on COVID-19 guidelines; see Section 8.1): There 
is no risk of injury from the wrist-actigraph to measure sleep, though it may feel like a 
slight inconvenience wearing a wrist device for 14 days. There may be a risk of allergy 
to the metal of the actigraph device.  
Confidentiality of data: Although every reasonable effort will be taken, confidentiality 
on web-based surveys cannot be guaranteed. It is possible that information may be 
captured and used by others who are not associated with this study.  

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Inconvenience: There may be some burden associated with completing the 
questionnaires and attending intervention sessions.  
Worsening depressive symptoms and/or suicidal ideation: As is true for non-
perinatal individuals generally, participants with poor sleep quality may experience 
increases in depressive symptoms and/or suicidal ideation, independent from their 
involvement in the study. 
2.3.2 KNOWN POTENTIAL BENEFITS  
Previous research suggests that mindfulness-based interventions are associated with 
improvements in sleep14 and responses to pain15-17 in non-pregnant populations. All 
participants may benefit from ongoing monitoring of and referral for depression 
incidence or suicidality. In the long-term, there are substantial benefits to be gained by 
optimizing a mindfulness-based intervention to improve prenatal sleep.  
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
MBSR+PS Participants will be provided with a thorough description of the intervention 
prior to randomization, and notified that they can withdraw participation at any time 
without penalty. Given the physical and psychological consequences of poor sleep 
quality during pregnancy, we expect that the proposed intervention would be associated 
with improved outcomes. However, important precautions will be taken to minimize 
physical risks. Participants will be provided the American College of Obstetrics and 
Gynecology list of indicators to terminate exercise. Participants will be advised to stop 
the physical activity if these signs are present, and to contact their obstetric health care 
provider. We will ask participants to alert us if they experience an increase in daytime 
sleepiness, and will advise them about the risks of driving or doing any activity where 
severe sleepiness puts them at danger, and will instruct them to take naps if they feel 
sleepy. 
Self-report questionnaires: Participants will be allowed to skip any questions they do 
not feel comfortable answering. One exception is that participants will be informed 
during the initial screening that skipping questions that are necessary for determining 
eligibility may preclude their ability to participate in the study. Additionally, because all 
questionnaires will be completed online, participants can complete them in a location 
and at a pace that feels comfortable to them. 
Actigraphy (optional depending on COVID-19 guidelines; see Section 8.1): In case 
of allergy, participants can wear the monitor over their sleeve or use a wrist sports 
sweatband to protect their skin.  
Confidentiality: All data will be handled with the utmost attention to participants’ 
confidentiality. Participants will be assigned unique, coded, confidential identifiers that 
will be used to label all data forms, data entries, and questionnaires. The key linking the 
participants’ identity to their unique coded identifier will be stored on a cloud-based 
collaboration tool that uses access controls and encryption, and is safe for storing 
protected health information. Access to all data will be limited to the PI and trained, 

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authorized study staff. 
One limit to confidentiality is if a participant indicates she is at imminent risk of harming 
herself. If a participant endorses PHQ-9 item 9, a pop-up will immediately appear with 
instructions to call 911 or go to the nearest emergency room for a life-threatening 
emergency. Additionally, email triggers will immediately notify study staff, who will call to 
conduct a risk assessment using the Columbia-Suicide Severity Rating Scale (C-
SSRS). At the beginning of the C-SSRS assessment, study staff will ask the participant 
for her current location. Study staff will provide psychological referrals for low to medium 
risk. For immediate risk, the study staff will direct the participant to the nearest 
emergency room and/or to call 911. If the participant declines, the study staff will call the 
participant’s local emergency services number, which will be recorded in the participant 
tracking database at enrollment. Study staff will immediately notify Co-Investigator Dr. 
Krystal, a psychiatrist with experience working with depressed and suicidal individuals, 
anytime a participant endorses suicidality. He will provide further supervision as 
deemed necessary and will determine whether additional follow-up assessment is 
indicated. Principal Investigator Dr. Felder, a licensed clinical psychologist with 
experience working with depressed perinatal women, will be a back-up if Dr. Krystal is 
unavailable. 
Worsening depressive symptoms: Participants will be instructed to make immediate 
contact with study personnel with any questions or concerns regarding worsening 
depression symptoms. At enrollment, we will provide contact information for Dr. Krystal, 
Dr. Felder, therapeutic resources, and crisis hotlines. We will closely monitor depressive 
symptom severity via weekly administration of the PHQ-9. Study staff will recommend 
that any participant who scores above the PHQ-9 cutoff (≥10) notify her obstetrician. 
Additionally, study staff will recommend that participants who score above the cutoff 
seek treatment for depression and will provide local resources using the Postpartum 
Support International “Find Local Support and Help” resource 
(https://www.postpartum.net/get-help/locations/).  
Inconvenience: Every effort will be taken to reduce participant burden, and participants 
will be compensated for their time and effort.   
 
 
 
 
 
 
 
 

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3 
OBJECTIVES AND ENDPOINTS  
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION 
FOR 
ENDPOINTS 
METRIC 
Primary 
 
 
 
To determine 
acceptability 
 
1. Willingness to 
be randomized 
2. Treatment 
initiation 
3. Reasons for 
attrition 
4. Satisfaction 
One of the 
primary study 
objectives of this 
pilot RCT is to 
determine the 
acceptability of 
the MBSR+PS 
intervention and 
the study 
procedures.   
1. Among women 
determined to 
be eligible to 
participate, we 
aim for ≥80% to 
indicate 
willingness to be 
randomized 
2. We aim for 
≥85% 
MBSR+PS 
participants to 
attend at least 
one session of 
MBSR and the 
PS supplement 
3. Assessed 
qualitatively 
4. Among 
participants 
randomized to 
MBSR+PS, we 
aim for a total 
score ≥ 24 on 
the Client 
Satisfaction 
Questionnaire 
To determine 
feasibility 
1. Yield of 
eligible 
participants 
2. Number 
randomized 
3. Retention rate 
One of the 
primary study 
objectives of this 
pilot RCT is to 
determine the 
feasibility of the 
MBSR+PS 
intervention and 
1. Defined as # 
Eligible / # 
Assessed for 
Eligibility 
2. N=50 within 
study timeline 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION 
FOR 
ENDPOINTS 
METRIC 
4. Completeness 
5. Missingness 
the study 
procedures.   
3. Our goal is for 
≥80% of 
randomized 
participants to 
complete 
endpoint 
measures 
4. For a measure 
to be 
considered 
complete, at 
least 95% of 
items must be 
completed. We 
aim for ≥ 95% of 
participants who 
are participating 
at a particular 
time point to 
complete each 
scale 
5. Explore patterns 
of incomplete 
data and 
investigate 
possible 
missingness 
mechanisms 
(i.e., missing 
completely at 
random, missing 
at random, 
missing not at 
random). 
To determine 
adherence 
1. Session 
attendance 
2. Home practice 
completion 
One of the 
primary study 
objectives of this 
pilot RCT is to 
determine 
participant 
1. We aim for an 
average of at 
least 50% of 
MBSR and PS 
supplement 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION 
FOR 
ENDPOINTS 
METRIC 
adherence to the 
MBSR+PS 
intervention.   
sessions 
attended. 
2. We will examine 
the frequency 
and duration of 
formal and 
informal 
practices 
Secondary/Exploratory  
 
 
To explore evidence of 
change in 
psychological 
mediators 
1. 14-day daily 
diary 
2. Validated 
retrospective 
measures of 
psychological 
constructs 
hypothesized 
as mediators  
A secondary 
study objective is 
to explore group 
differences in 
change on 
potential 
mechanistic 
outcomes.  
Non-acceptance, 
avoidance, self-
compassion, 
rumination, worry, 
mindfulness, as 
measured by 14-
day daily diary and 
validated 
retrospective 
measures (Self-
Compassion Scale-
Short Form; 
Rumination-
Reflection 
Questionnaire; Five 
Facet Mindfulness 
Questionnaire; 
Coping Strategy 
Scale) 
To explore between-
group differences in 
sleep  
Subjective sleep  
A secondary 
objective is to 
explore change in 
clinical outcome. 
In future 
research, we 
expect that our 
primary clinical 
endpoint will be 
global sleep 
quality. 
Pittsburgh Sleep 
Quality Index 
scores (primary); 
Insomnia Severity 
Index; 
Dysfunctional 
Beliefs About 
Sleep; Measures 
for coping with 
sleep disturbances; 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION 
FOR 
ENDPOINTS 
METRIC 
Worry about sleep 
(secondary) 
 
To explore group 
differences in other 
critical clinical 
outcomes 
1. Depressive 
symptoms 
2. Anxiety 
symptoms 
3. Stress 
A secondary 
objective is to 
explore change in 
mental health 
clinical outcomes.  
1. PHQ-9 
2. PROMIS 6-item 
anxiety 
measures 
3. Perceived 
Stress Scale 
 
4 
STUDY DESIGN 
4.1 OVERALL DESIGN 
Hypotheses: The primary goal of this pilot RCT is to test acceptability, feasibility, and 
adherence using the metrics described above. Secondarily, we will explore evidence of 
change in primary mechanistic outcomes (e.g., psychological responses to nightly 
physical symptoms), and group differences in our primary clinical outcome (i.e., sleep 
quality).  
Trial phase: This feasibility trial is considered trial Stage 1B in the NIH Stage Model for 
Behavioral Intervention Development. 
Trial design: This is a single-site, randomized controlled trial comparing MBSR+PS to 
TAU.  
Randomization (see also section 6.3): Participants will be randomized to MBSR+PS 
or TAU after the baseline assessment. Randomization will be blocked to reduce 
imbalance in condition assignment and conducted by an independent investigator. 
Consistent with standard procedures, the independent investigator may use multiple 
block lengths but will not tell study staff the number or length of blocks. Participants will 
be notified of their assignment by phone and email.  
We considered stratifying randomization by gestational age but decided against it for 
the following reasons: 1) we are enrolling participants in a fairly narrow gestational age 
range (12-28 weeks gestation), reducing the need for stratification; 2) using stratification 
in a blocked randomization scheme may make it too easy to anticipate future 
allocations; 3) the need for stratification is low considering we have the computing 
power to adjust for unbalanced covariates if needed; and 4) there may be significant 

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practical challenges meeting enrollment and timeline targets with both a narrow 
gestational age range and stratification. We will implement stratified randomization in 
future research if data from this feasibility trial indicate it is necessary.  
Study interventions: Participants are randomized to one of two conditions: MBSR+PS 
+ TAU or TAU alone.  
For TAU, participants are permitted to receive standard care for prenatal sleep 
disturbance. That is, there are no constraints on treatment, including medication or 
psychotherapy, with the exception of asking participants to refrain from participating in 
non-study mindfulness practice.  
Additionally, MBSR+PS participants will receive standard MBSR plus supplemental 
prenatal sleep content. The MBSR groups will be offered via Zoom through publicly-
available, existing MBSR program courses that are linked to an academic medical 
center or hospital.  Participants will be randomized to MBSR programs at the UCSF 
Osher Center for Integrative Medicine, Brown University Mindfulness Center, or the 
UCSD Center for Mindfulness. If needed to meet enrollment targets, participants may 
also be randomized to MBSR programs taught at the UMass Memorial Health Center 
for Mindfulness and Bob Stahl’s ART Mindfulness Program. Participants will only be 
randomized to MBSR courses for which the instructor confirms that there are no 
substantial modifications to the standard curriculum. All MBSR groups will be comprised 
of heterogenous groups, including non-pregnant people.  
 
The prenatal sleep content: 
• Draws material from the mindfulness-based therapy for insomnia program, the 
research on cognitive behavior therapy that specialized advisor Dr. Rachel 
Manber and I have done with pregnant women with insomnia, and the 
mindfulness-based childbirth and parenting program. 
• Will be delivered via Zoom in brief (≤30 minutes) weekly sessions designed to 
supplement the MBSR course by an instructor with behavioral sleep medicine 
training. 
• Can be delivered to small groups of pregnant women or one-on-one. 
 
4.2 SCIENTIFIC RATIONALE FOR STUDY DESIGN 
We selected TAU as the comparator group because our goals are to document clinically 
significant signal above and beyond usual care and to maximize between-group 
differences in the primary mechanistic outcomes33 at this early stage of research. 
Further, TAU is a clinically relevant comparator by nature. We opted against a no 
treatment comparator due to ethical concerns about withholding treatments that the 
population may need and otherwise receive. 
4.3 JUSTIFICATION FOR INTERVENTION 
We will deliver MBSR+PS via video conferencing (i.e., Zoom platform) instead of via in-
person sessions for several reasons. First, delivering the intervention remotely affords 

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us more flexibility and the ability to continue study activities even in the context of 
potential COVID-19 shelter-in-place orders. Second, pregnant women may have a lower 
tolerance for risk for attending in-person visits when there are spikes in COVID-19 
activity. Third, we want to develop a program that has high potential for scalability and 
ultimately plan to deliver the intervention remotely in efficacy testing. Thus, the feedback 
we will get in this feasibility trial will be more relevant. Finally, delivering the intervention 
remotely is responsive to focus group feedback that women do not want an all in-person 
intervention. 
MBSR will be offered in its typical session format: in 8 weekly sessions with an all-day 
retreat. The prenatal sleep content will be offered in 6-8 weekly brief sessions designed 
to be 30 minutes or less. Data will be analyzed on an intent-to-treat basis, and we aim 
for an average percentage of sessions attended ≥ 50%.  
4.4 END-OF-STUDY DEFINITION 
A participant is considered to have completed the study once she has completed the 
endpoint measures. The end of the study is defined as the final participant’s completion 
of the endpoint measures shown in the Schedule of Activities (SoA), Section 1.3. 
5 
STUDY POPULATION  
5.1 INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the 
following criteria: 
1. Currently pregnant 8-28 weeks gestation. This ensures that participants can 
learn strategies to improve their sleep before the end of the third trimester when 
sleep quality is the poorest, and can complete the intervention prior to birth. 
2. 18 years or older. Adolescents have unique sleep needs that are not addressed 
in the proposed intervention. 
3. Daily access to a web-enabled computer, phone, or tablet. Access is necessary 
to participate in the weekly interventions sessions, which are delivered via Zoom, 
and for the 14-day daily online sleep diaries, in which participants receive an 
automated email or text message with a personalized survey link to complete 
upon awakening each morning. 
4. Ability to read and speak English, and to provide informed consent. The 
intervention will be delivered in English, and we do not have the capacity, given 
the resources available in this project, to translate all course material and 
conduct groups in another language.   
5. Poor sleep quality (PSQI > 5). The ultimate goal of the proposed research is to 
improve poor sleep quality.  
 

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5.2 EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation 
in this study: 
1. Self-reported sleep disorder not likely to improve with MBSR+PS (e.g., sleep 
apnea, narcolepsy, parasomnia, circadian rhythm disorder).  
2. Shift-work or nighttime caregiving responsibilities. Irregular sleep/wake patterns 
would make it difficult to evaluate the impact of the intervention. 
3. Psychological, medical, or other issues that necessitate priority treatment or that 
would preclude participation (e.g., active suicidality, probable depression, 
psychosis, on bed rest, multiple gestation).  
4. Current regular mindfulness practice (>20 minutes/week). Regular mindfulness 
practice aside from the study intervention would risk contamination of study 
outcomes.  
5.3 LIFESTYLE CONSIDERATIONS 
During this study, participants are asked to refrain from participating in non-study 
mindfulness practices. At endpoint, we will measure participation in non-study 
mindfulness practices. We view this as informative data to gather in this feasibility trial, 
and will not withdraw participants for participating in non-study mindfulness practices. 
5.4 SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in this study but 
are not subsequently assigned to the study intervention or entered in the study. 
Individuals who do not meet the criteria for participation in this trial (screen failure) 
because of meeting one or more exclusion criteria that are likely to change over time 
may be rescreened. An example includes the lifting of bed rest restrictions previously in 
place. Rescreened participants will be assigned the same participant number as for the 
initial screening. 
5.5 STRATEGIES FOR RECRUITMENT AND RETENTION 
Anticipated number to be screened: We conservatively estimate that we may need to 
screen approximately 550 women to reach the target enrollment size of 50. This 
estimate is based on our previous trial evaluating digital cognitive behavioral therapy for 
prenatal insomnia, which used more stringent eligibility criteria.  
Sample size and demographics: We will randomize 50 participants with the goal of 
obtaining endpoint data from 40 (50 randomized x 80% anticipated retention = 40 with 
endpoint data). The purpose of the proposed research is to optimize MBSR+PS to 
improve poor sleep quality among pregnant women. Therefore, all participants will be 
women. There are no 12 or exclusion criteria based on race or ethnicity. Minority 

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inclusion will be representative of the San Francisco Bay Area 2010 Census results. We 
expect that approximately 50% of participants will be White, and approximately 15% will 
be Hispanic or Latina.  
Recruitment sources: We will primarily recruit participants from two sources: 1) UCSF 
Obstetrics and Gynecology clinics via electronic health record, direct mail, and 
electronic flyers in waiting rooms (anticipated n = 25), and 2) Facebook advertisements 
(anticipated n = 25). We have successfully employed these methods in previous clinical 
trials with pregnant women at UCSF.  
If needed, we will recruit participants via listservs, social media groups and accounts, 
and publications that serve a pregnant audience, and post ads in community, medical, 
and retail settings (e.g., grocery stores, maternity clothing stores, toy stores).  
We will ensure a diverse, representative sample by using advertisement images 
featuring racially and ethnically diverse pregnant women and by using targeted 
recruitment text (e.g., “Recruiting pregnant Latina women”). If needed, we will utilize 
Facebook’s audience selection tool to display our ads in zip codes that have a higher 
proportion of racially and ethnically diverse populations.  
Procedure for identifying participants: For women recruited through UCSF 
Obstetrics and Gynecology clinics, MyChart (Apex) conducts a search for patients 
based on the study’s inclusion and exclusion criteria. This is a completely computer-
aided search, meaning the computer – not a person – searches patient charts. When a 
patient is identified as potentially eligible, they receive an email from MyChart that says 
to log in to MyChart to read about a study they might be interested in. The email is short 
and is the same for every recipient—there is no patient-specific, study-specific or 
disease information in it. When the patient logs into MyChart, there is a new “Research” 
tab with template information about participating in research and how to opt out of 
receiving recruitment messages. Then, the patient can click through to learn about a 
specific study they may be eligible for. The patient has the option of clicking a 
link/button to let the study team know that they are interested in learning more about the 
study. Only if the patient takes this action will the study team receive information about 
the patient. If the patient clicks “No thanks” or simply does not respond, they will not be 
contacted by the study team, they won’t receive any follow-up emails from MyChart 
about this study, and their information will not be shared with the study team. To 
address racial and ethnic disparities that exist in MyChart enrollment, we will also 
collaborate with the CTSI Participant Recruitment Program (PRP) to send paper letters 
to patients who are not enrolled in MyChart. CTSI PRP will act as an honest broker of 
the EHR data and sends letters to the cohort directly, ensuring privacy and 
confidentiality of patients identified. The data extract will be done using APeX reports 
and will be downloaded and stored in the CTSI PRP MyResearch account. The CTSI 
PRP will coordinate the mailing on behalf of the study and will send the Dear Patient 
letter to UCSF patients identified in these reports. Interested subjects will contact the 
study staff as described in the letter. Protected data elements included in the data pull 
may include MRN, name, mailing address, and diagnosis or encounter date. 
 

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Women who view our IRB-approved ads on Facebook will be directed to complete the 
online eligibility survey or to contact study staff directly to learn more about the study.  
 
Accrual rate: We will begin randomizing women in September 2021 to complete data 
collection by August 2022.  
Justification for inclusion of vulnerable participants: The rationale for our focus on 
the vulnerable population of pregnant women is informed by the exceedingly high 
prevalence of poor sleep quality during this critical lifecycle phase, the consequences of 
prenatal poor sleep quality, and the limitations of existing interventions. 
Retention strategies: We will utilize the following methods to encourage measure 
completion, which have been successful in our previous clinical trials with pregnant 
women: 
1. Conduct an orientation session prior to randomization, which is shown to 
increase adherence and retention. Participants will learn about: the scientific 
importance of the trial; what participation entails; rationale for the control 
condition and random assignment; and the effect of attrition bias. Participants will 
be asked to generate two pros and two cons of participating in the study and not 
participating in the study, and to carefully consider whether or not to participate. 
2. Create a project identity that participants can recognize using a study logo, and 
similar colors and fonts on trial materials.  
3. Write protocols to address common participant questions. 
4. Embody a “gracious and tenacious” approach by making multiple, standardized 
attempts to contact participants via phone, email, and text message to complete 
measures. 
5. Send birthday cards to maintain connection with participants. 
6. Request contact information for someone we have permission to contact if we 
lose touch with participant. 
7. Provide monetary incentives for completing measures: 
a. $25 upon completion of baseline self-report measures 
b. Up to $100 for baseline daily diaries (depending on number of diaries 
completed)* 
c. $25 upon completion of endpoint self-report measures 
d. Up to $100 for endpoint daily diaries (depending on number of diaries 
completed)* 

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*If participant is wearing wrist actigraph (optional depending on local COVID-19 
guidelines; see Section 8.1), then compensation will be sent upon study team’s receipt 
of actigraph. 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
ADMINISTRATION 
6.1.1 STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION 
DESCRIPTION 
Participants will be randomly assigned to either the intervention condition, mindfulness-
based stress reduction plus prenatal sleep supplement (MBSR+PS) or the control 
condition, treatment as usual (TAU).  
The MBSR+PS program involves standard MBSR plus supplementary prenatal sleep  
content. The prenatal sleep content includes psychoeducation about sleep during 
pregnancy, applies mindfulness principles to sleep, and teaches behavioral principles 
for improving sleep. In our preliminary work, pregnant women described maladaptive 
behavioral responses that may perpetuate sleep problems, such as lying in bed for 
hours looking at their phone. Thus, the intervention also draws from cognitive behavior 
therapy for insomnia (CBT-I) and the mindfulness-based therapy for insomnia (MBTI) 
program to integrate behavioral recommendations for improving sleep with mindfulness 
techniques (e.g., stimulus control). 
All participants will be asked to refrain from participating in non-study mindfulness 
programs to prevent contamination. There are no other constraints on treatment, 
including medication or psychotherapy (treatment as usual; TAU). If a participant 
develops a sleep disorder (e.g., sleep apnea) over the course of the study, we will 
provide a list of referrals for further evaluation and treatment; such participants will be 
allowed to remain in the study.  
6.1.2 ADMINISTRATION AND/OR DOSING 
The full-dose MBSR+PS program will consist of: 
Standard MBSR: 
• 8 weekly sessions 
• All day retreat  
• Administered by a trained and vetted MBSR instructor via Zoom 
• Delivered to heterogenous groups, including non-pregnant women 
Prenatal Sleep Content: 
• 6-8 weekly brief sessions (≤ 30 minutes) via Zoom  
• Flexibly designed to be delivered 1:1 or to small groups of pregnant women 

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• Delivered by an instructor with behavioral sleep medicine training 
6.2 FIDELITY 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
Prior to randomizing participants to a particular MBSR class, we will request that the 
class instructor complete a brief survey with the following items: 
1. In the MBSR classes you teach, do you make any substantial modifications to 
the standard curriculum? If yes, please describe. (We will not randomize 
participants to MBSR classes with substantial modifications to the standard 
curriculum) 
2. How many years of experience do you have teaching MBSR? (This descriptive 
data will be reported in publications; We will not exclude MBSR classes based on 
instructor responses to this item.) 
3. Over the past 3 years, how many total days have you spent at  mindfulness 
retreats? (This descriptive data will be reported in publications; We will not 
exclude MBSR classes based on instructor responses to this item.) 
 
All prenatal sleep content sessions will be recorded on the Zoom platform. Dr. Felder 
will review 10% of audio-recorded sessions to ensure that the key elements of the 
curriculum content are addressed.  
6.3 MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
Randomization will be blocked to reduce imbalance in condition assignment and 
conducted by an independent investigator. Consistent with standard procedures, the 
independent investigator may use multiple block lengths but will not tell study staff the 
number or length of blocks. Participants will be notified of their assignment by phone 
and email. 
We have carefully considered the issue of blinding, and have decided the following: 
• Principal investigator: Blinded to condition assignment. 
• Randomizer: Unblinded by necessity but will be independent from the study and 
have no access to the data and/or influence on outcome assessments. 
• Project coordinator and research assistants: Unblinded to condition 
assignment in order to permit day-to-day management of the trial, including 
notifying participants of randomization, assisting the clinician with intervention 
delivery, and responding to participant questions. Although these staff members 
will assist with data collection, all measures are self-report via online surveys. No 
measures are interviews or clinician-rated, thus mitigating concerns about the 
effect of unblinding on outcome assessment. 

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• Data manager: Blinded to condition assignment. 
• Participants and clinicians: Unblinded to condition assignment by necessity 
because we are comparing MBSR+PS to treatment as usual. 
We do not anticipate any situations that would require breaking the study blind. Drs. 
Krystal and Hecht are unblinded and able to respond to safety concerns and serious 
adverse events. 
6.4 STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
ADHERENCE 
As in our previous research, we will use a REDCap database to track and retain 
participants for follow-up assessments. The tracking file will contain each participant’s 
current status in the study (e.g., enrolled, completed); dates when consent documents 
are completed, when measures are due, and when measures are completed; and an 
open text field for comments.  
Adherence is operationalized as session attendance and home practice completion. We 
will enter weekly MBSR+PS attendance into the REDCap database. Participants will be 
asked to complete a brief daily survey of home practice completion, and home practice 
completion will be recorded into the REDCap database. Finally, we will track whether 
participants access and download intervention materials. 
To permit intention-to-treat analyses, we will follow participants even if they cease to 
adhere to the protocol, regardless of condition assignment. 
6.5 CONCOMITANT THERAPY 
At endpoint, we will assess the type, frequency, and duration of non-study treatments, 
including the use of pharmacotherapy, psychotherapy, natural remedies, and psychiatric 
hospitalization.  
6.5.1 RESCUE THERAPY 
N/A 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL 
MANIPULATION 
We do not anticipate any reasons for the investigators to discontinue the study 
intervention for participants. Participants can decide to discontinue the study 
intervention and to continue participating in the study by completing follow-up 

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measures. Participants who become ineligible (e.g., no longer pregnant due to 
miscarriage) will have the option to continue both the intervention and the study. 
If a participant discontinues the intervention, we will record their reason(s) for 
discontinuing the intervention. 
If the participant is due to complete assessments within 2 weeks of discontinuing the 
study intervention, those assessments will be administered at the time of 
discontinuation; if the next scheduled assessments are more than 2 weeks from the 
discontinuation date, the discontinued participant will wait for the next scheduled 
assessment. Thereafter, the participant will be included in all future scheduled 
assessments, even though not participating in the intervention. 
7.2 PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon 
request. We do not anticipate that the investigators will discontinue any participant from 
the study.  
7.3 LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up at a particular timepoint if she fails to 
respond within the allowable response window (See table in Section 1.3). The following 
actions will be taken to minimize loss to follow-up: 
• Study staff will contact participants via a range of methods (email, phone, text, 
letter) at least 3 times to remind them to complete study measures within the 
allowable response window. These contact attempts will be documented in the 
participant tracking database.  
• If the above attempts are unsuccessful, study staff will contact the participant’s 
secondary contact person to find out the best method of reaching the participant 
and/or to have the secondary contact person ask the study participant to contact 
study staff. 
• Should the participant continue to be unreachable at a particular timepoint, study 
staff will continue to send follow-up assessments at each subsequent timepoint. 
Participants will not be withdrawn due to lost to follow-up at any timepoint. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
See the Table in Section 1.3 for an overview of timepoints, allowable response 
windows, and measurement schedule.  
Screening timepoint: Participant demographic data will be collected to determine 
eligibility (e.g., age) and to fully characterize the sample (e.g., race, ethnicity, highest 

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level of education attained, income, marital status, number of children and their ages, 
zip code, insurance type, employment status). Eligibility criteria will be assessed using a 
screening survey that assesses:  
• self-report of pregnancy status and gestational age in weeks 
• confirmation of pregnancy via an ultrasound image, after visit summary, 
appointment reminder, bill, or similar document that includes participant name 
and date. Women can choose to upload this documentation into the eligibility 
survey, display the documentation during the orientation visit, or send the 
document via secure email.  
• self-reported daily access to a web-enabled computer, phone, or tablet self-
reported ability to read and speak English  
• self-reported diagnosis of sleep apnea, narcolepsy, parasomnia, or circadian 
rhythm disorder  
• validated Facco algorithm to screen for sleep apnea during pregnancy 
• validated Morning-Eveningness Questionnaire to screen for circadian rhythm 
disorder  
• self-reported experience of sleepwalking, sleeptalking, nightmares to assess for 
parasomnia  
• self-reported night shift work in the past month or next month  
• self-reported nighttime caregiving responsibilities 
• validated Patient Health Questionnaire-9 to assess for depression and/or 
suicidality  
• self-reported diagnosis of schizophrenia or bipolar disorder 
• self-reported on bed rest 
• self-reported pregnancy with multiples  
Baseline timepoint: Participants will complete two types of assessments at the 
baseline timepoint: 14 daily sleep diaries and outcome measures. 
14 day online daily sleep diaries: To assess the mechanisms of pregnancy-related 
physical symptoms-poor sleep association, we will use daily diary methods to 
capture data on the dynamic, longitudinal associations between nightly physical 
symptoms, psychological responses (i.e., acceptance, self-compassion, rumination, 
worry, mindfulness, maladaptive pain coping), and sleep quality. Each morning for 
14 consecutive days, participants will complete a diary assessing: 

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• Last night's sleep using the validated consensus sleep diary  
• Disruptors of sleep (physical symptoms, anxiety/worry, mind racing)  
• Psychological responses to nightly physical symptoms 
Depending on local COVID-19 guidelines, we may also use wrist-actigraphy to 
assess our secondary clinical outcome, objective sleep behaviors (total sleep time, 
sleep latency, wake after sleep onset, number of awakenings, sleep efficiency). We 
will collect these data only if local guidelines permit research as usual. Sending and 
receiving the wrist actigraphs requires multiple trips per week to FedEx, and we do 
not want to risk staff safety to collect this secondary outcome. Further, we have 
adequate feasibility data collecting actigraphy data from 50 pregnant women in our 
preliminary research (Aim 1 of K23).  
Outcome measures: Consistent with our preliminary research (Aim 1 of K23), we 
will collect data on nightly physical symptoms, psychological mediators, and sleep 
quality using retrospective, self-report measures. We received feedback from Aim 1 
participants that completing these online measures was not burdensome, and we 
had no missing data. 
• Pregnancy Symptoms Inventory previously adapted to measure nightly sleep 
disturbances  
• Measures of psychological mediators:  
o Self-Compassion Scale - Short Form  
o Rumination-Reflection Questionnaire  
o Five Facet Mindfulness Questionnaire  
o Coping Strategy Scale  
• Measures of sleep: 
o Pittsburgh Sleep Quality Index 
o Insomnia Severity Index 
o Dysfunctional Beliefs About Sleep 
o Measures for coping with sleep disturbances  
o Worry about sleep   
• Other clinical outcomes: 
o Patient Health Questionnaire-9 

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o PROMIS 6-item anxiety measure 
o Perceived Stress Scale 
o Contemplative practices and stress management techniques  
Daily measures: Participants randomized to MBSR+PS will be asked to complete a 
brief daily home practice measure and the consensus sleep diary from the first until the 
last intervention session. 
Weekly measures: Participants will complete a depression measure (Patient Health 
Questionnaire-9) once per week from randomization until endpoint.  
Endpoint measures: Participants will complete the same outcome measures as at the 
baseline timepoint, as well as the Client Satisfaction Questionnaire and adverse events 
questionnaire. 
8.2 SAFETY ASSESSMENTS 
We plan to use the Patient Health Questionnaire-9 to monitor depressive symptom 
severity. PHQ-9 scores range from 0-27, with scores ≥ 10 indicating moderate-to-severe 
depression. Item 9 assesses “thoughts that you would be better off dead, or of hurting 
yourself in some way.” At screening, women with PHQ-9 ≥ 10 or who endorse item 9 
will be excluded from participation. Among enrolled participants, we will closely monitor 
depressive symptom severity and suicidal ideation via weekly administration of the 
PHQ-9. Qualified study personnel will make appropriate referral for community care for 
participants with PHQ-9 ≥ 10.  
If a participant endorses the self-harm item of the PHQ-9, a pop-up will immediately 
appear with instructions to call 911 or go to the nearest emergency room for a life-
threatening emergency. Additionally, email triggers will immediately notify study staff, 
who will call to conduct a risk assessment using the Columbia-Suicide Severity Rating 
Scale (C-SSRS).  
At the beginning of the C-SSRS assessment, study staff will ask the participant for her 
current location. Study staff will provide psychological referrals for low to medium risk. 
For immediate risk, the study staff will direct the participant to the nearest emergency 
room and/or to call 911. If the participant declines, the study staff will call the 
participant’s local emergency services number, which will be recorded in the participant 
tracking database at enrollment. Study staff will immediately notify co-mentor Dr. 
Krystal, a psychiatrist with experience working with depressed and suicidal individuals, 
anytime a participant endorses suicidality on the PHQ-9. He will provide further 
supervision as deemed necessary and will determine whether additional follow-up 
assessment is indicated. Principal Investigator Dr. Felder, a licensed clinical 
psychologist with experience working with depressed perinatal women, will be a back-
up if Dr. Krystal is unavailable.  

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Because suicidal impulses can change rapidly, participants will be instructed to make 
immediate contact with study personnel with any issues, questions, or concerns 
regarding worsening symptoms. At enrollment, we will provide contact information for 
Dr. Felder, Dr. Krystal, local therapeutic resources, and crisis hotlines so that 
participants can have the phone numbers readily accessible. 
8.3 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.3.1 DEFINITION OF ADVERSE EVENTS 
This protocol uses the definition of adverse events from the UCSF Clinical Research 
HUB: Adverse events are events that are undesirable and unintended, although not 
necessarily unexpected, effect of the research occurring in human subjects as a result 
of (a) the interventions and interactions used in the research; or (b) the collection of 
identifiable private information under the research.  
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
A Serious Adverse Event is defined as any Adverse Event that results in any of the 
following outcomes: 
• Death, 
• Life-threatening adverse experience*, 
• Inpatient hospitalization or prolongation of existing hospitalization, 
• Persistent or significant disability/incapacity, 
• Congenital anomaly/birth defect, or cancer, or 
• Any other experience that suggests a significant hazard, contraindication, side 
effect or precaution that may require medical or surgical intervention to prevent 
one of the outcomes listed above, 
• Event that changes the risk/benefit ratio of the study.  
* A life-threatening adverse experience is any AE that places the patient or subject, in 
the view of the investigator, at immediate risk of death from the reaction as it occurred, 
i.e., it does not include a reaction that, had it occurred in a more severe form, might 
have caused death. 
The events below are considered expected and will not be reported to the IRB: 
• Increased sleepiness, which is a common short-term side effect of the sleep 
consolidation component of MBSR+PS 
• Poorer sleep quality, which is normative as pregnancy advances 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 

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8.3.3.1 SEVERITY OF EVENT 
Adverse events will be assessed by the principal investigator with co-investigator Dr. 
Krystal, who has experience assessing psychiatric adverse events, and/or co-
investigator Dr. Hecht, who has experience assessing medical adverse events. The 
following guidelines will be used to describe severity.  
• Mild: Events require minimal or no treatment and do not interfere with the 
participant’s daily activities.  
• Moderate: Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
• Severe: Events interrupt a participant’s usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually potentially 
life-threatening or incapacitating. Of note, the term “severe” does not necessarily 
equate to “serious”. 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL 
MANIPULATION 
All adverse events (AEs) will have their relationship to study procedures, including the 
intervention, assessed by an appropriately-trained clinician based on temporal 
relationship and his/her clinical judgment. The degree of certainty about causality will be 
graded using the categories below.  
• Definitely related: An AE is definitely related to study participation if it is clear 
that the event was caused by study participation. A definitely related event has a 
strong temporal relationship and an alternative cause is unlikely. 
• Probably related: An AE is probably related when there is a reasonable 
possibility that the event is likely to have been caused by study participation. The 
AE has a timely relationship to the study procedure(s) and follows a known 
pattern of response, but a potential alternative cause may be present. 
• Possibly related: An AE is possibly related when there is a reasonable 
possibility that the event might have been caused by study participation. A 
possibly related event may follow no known pattern of response and an 
alternative cause seems more likely. In other circumstances there may be 
significant uncertainty about the cause of the event, or a possible relationship to 
study participation cannot reasonably be ruled out. 
• Unrelated: The cause of the AE is known and the event is in no way related to 
any aspect of study participation. If there is any uncertainty regarding AE 
causality then the event must be assessed as possibly related to research 
participation and reported to the IRB as indicated. Often, the cause of an 
unrelated AE is disease progression. 

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8.3.3.3 EXPECTEDNESS  
An AE that may be reasonably anticipated to occur as a result of the study procedures 
or study participation and should thus be described in the research proposal, the 
informed consent document, or is part of the normal disease process or progression. An 
AE or suspected adverse reaction is considered "unexpected" if it is unlikely to occur in 
the study population, or it is unlikely to occur at the severity that has been observed. 
An adverse event is defined as being unexpected if the event exceeds the nature, 
severity or frequency described in the current IRB Application including the protocol and 
consent form. An unexpected AE also includes any AE that meets any of the following 
criteria: 
• Results in subject withdrawal from study participation, 
• Due to a deviation from the IRB approved study protocol 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND 
FOLLOW-UP 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to 
the attention of study personnel when participants complete the adverse event 
questionnaire or when participants spontaneously report adverse events.  
All AEs, not otherwise precluded per the protocol, will be captured on an adverse event 
report form. Information to be collected includes event description, time of onset, 
clinician’s assessment of severity, relationship to study procedures, and time of 
resolution/stabilization of the event. All AEs occurring while on study will be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
Any medical or psychiatric condition that is present at the time that the participant is 
screened will be considered as baseline and not reported as an AE. However, if the 
study participant’s condition deteriorates at any time during the study, it will be recorded 
as an AE.  
Changes in the severity of an AE will be documented to allow an assessment of the 
duration of the event at each level of severity to be performed. Documentation of onset 
and duration of each episode will be maintained for AEs characterized as intermittent. 
Dr. Felder will record events with start dates occurring any time after randomization  
until the last day of study participation. At endpoint, the investigator will inquire about 
the occurrence of AE/SAEs since randomization. 
8.3.5 ADVERSE EVENT REPORTING  
Internal (on-site) adverse events that the PI determines to be 1. Definitely, probably or 
possibly related AND 2 Serious or unexpected will be reported to the IRB within 5 
working days of UCSF PI awareness. Individual reports of AEs determined to be 

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unrelated to research participation will not be reported to the IRB. Instead, these events 
will be documented, referenced and retained in the PI’s study files for follow-up. 
The events below are considered expected and will not be reported to the IRB: 
• Increased sleepiness, which is a common short-term side effect of the sleep 
consolidation component of MBSR+PS 
• Poorer sleep quality, which is normative as pregnancy advances 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
SAEs that are unanticipated, serious, and possibly related to the study intervention will 
be reported to the Independent Monitoring Committee, UCSF IRB, and NCCIH in 
accordance with requirements.   
• Unexpected fatal or life-threatening AEs related to the intervention will be 
reported to the IRB, NCCIH Program Officer, and Independent Monitoring 
Committee immediately following the investigator’s awareness of the event. 
Other serious and unexpected AEs related to the intervention will be reported 
within 5 working days of the investigator’s awareness of the event. 
• Individual reports of internal (on-site) AEs determined to be unrelated to research 
participation will not be reported to the IRB. Instead, these events will be 
documented, referenced and retained in the PI’s study files for follow-up, and will 
be reported to NCCIH and the Independent Monitoring Committee on an annual 
basis. 
• All other AEs documented during the course of the trial will be reported to NCCIH 
on an annual basis by way of inclusion in the annual report and in the annual AE 
summary which will be provided to NCCIH and to the Independent Monitoring 
Committee. The Independent Monitoring Committee Report will state that all AEs 
have been reviewed. 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
N/A 
8.3.8 EVENTS OF SPECIAL INTEREST  
N/A 
8.3.9 REPORTING OF PREGNANCY  
N/A because pregnancy is an inclusion criterion for the study. 
8.4 UNANTICIPATED PROBLEMS 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 

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This protocol uses the UCSF Institutional Review Board definition of Unanticipated 
Problems: An unanticipated problem is an unexpected, research-related event where 
the risk exceeds the nature, severity, or frequency described in the protocol, study 
consent form, or other study information previously reviewed and approved by the IRB. 
8.4.2  UNANTICIPATED PROBLEMS REPORTING  
The investigator will report unanticipated problems (UPs) to the UCSF Institutional 
Review Board (IRB) and Independent Monitoring Committee (IMC). The UP report will 
include the following information: 
• Protocol identifying information: protocol title and number, PI’s name, and the 
IRB project number 
• A detailed description of the event, incident, experience, or outcome  
• An explanation of the basis for determining that the event, incident, experience, 
or outcome represents an UP 
• A description of any changes to the protocol or other corrective actions that have 
been taken or are proposed in response to the UP 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline:   
• UPs that are serious adverse events (SAEs) will be reported to the IRB, IMC, and 
to the funding agency within 5 working days of the investigator becoming aware 
of the event  
• Any other UP will be reported to the IRB, IMC, and to the funding agency within 
10 days of the investigator becoming aware of the problem  
The UP report will be completed by qualified study staff and reviewed and signed off by 
the Principal Investigator. 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
N/A 
9 
STATISTICAL CONSIDERATIONS  
9.1 STATISTICAL HYPOTHESES 
Our primary objectives are to determine acceptability, feasibility, and adherence. We do 
not have formal hypotheses and descriptive statistics will be used to examine the 
metrics reported in the Section 3 table. A secondary objective is to explore group 
differences in change on potential mechanisms (e.g., psychological responses to nightly 
physical symptoms). Additionally, we will explore group differences in our primary 
clinical outcome, global sleep quality.  

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9.2 SAMPLE SIZE DETERMINATION 
We did not use a power analysis to determine sample size because our focus is on 
examining acceptability, feasibility, and adherence, versus on statistical analyses of 
efficacy. We believe 40 participants is adequate to investigate these metrics. Based on 
our previous and ongoing research, we anticipate that retention at 8-weeks post-
randomization will be ≥ 80%. Therefore, we will randomize 50 participants (50 
randomized x 80% retention = 40 with 8-weeks post-randomization data). 
9.3 POPULATIONS FOR ANALYSES 
All analyses will be conducted on the intention-to-treat sample defined as all 
randomized participants. Secondarily, analyses will be conducted on the per-protocol 
population of MBSR+PS participants who attended ³ 50% sessions and all TAU 
participants. 
9.4 STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
For descriptive statistics, categorical data will be presented with frequency and 
percentage. Continuous data will be presented with mean, standard deviation, median, 
and range. For exploratory inferential tests, statistical significance will be set at p <.05, 
and we will use 95% confidence intervals. Follow-up sensitivity analyses may include 
any factors that differed between groups at baseline.  
9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
The metrics used to calculate each endpoint are described in the Section 3 table. All 
primary endpoints will be examined descriptively. 
For the acceptability objective:  
• willingness to be randomized is binary 
• treatment initiation is binary 
• reasons for attrition is qualitative 
• satisfaction scores are interval 
For the feasibility objective:  
• yield of eligible participants is interval 
• number randomized is interval  
• retention rate is interval 

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• completeness is interval 
• missingness is qualitative 
For the adherence objective:  
• session attendance is interval 
• home practice completion is interval  
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Secondary endpoints are not dependent on findings of the primary endpoints. The 
metrics used to define each secondary endpoint are described in the Section 3 table.  
The current study is not powered to examine between-group differences in change on 
psychological mediators, sleep, or other clinical outcomes, but analyses will be 
conducted to serve as preliminary data. Given that data are nested within participants 
(repeated measures) violating assumptions of independence, multilevel modeling 
(MLM) methods will be used to explore group differences (MBSR+PS vs. TAU) in 
change psychological mediators, sleep, and other clinical outcomes. Clustering at the 
group level will be included in the exploratory models, and we will calculate the 
intraclass correlation for clustering for future study planning. The strength of the 
relationship between change in each psychological mediator and improvement in 
subjective sleep quality will also be examined. 
9.4.4 SAFETY ANALYSES 
N/A 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
We will collect the following baseline characteristics: age, race, ethnicity, highest level of 
education attained, income, marital status, number of children and their ages, zip code, 
insurance type, employment status, gestational age at enrollment. We will compare 
intervention groups using descriptive statistics.   
9.4.6 PLANNED INTERIM ANALYSES  
N/A 
9.4.7 SUB-GROUP ANALYSES 
Only adult females will be included in this study. We do not plan sub-group analyses.  
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 

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Individual participant data will not be listed by measure and time point in any 
publications. 
9.4.9 EXPLORATORY ANALYSES 
N/A 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
10.1.1 
INFORMED CONSENT PROCESS 
10.1.1.1 
CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS 
PROVIDED TO PARTICIPANTS 
Participants will view the screening and study consent forms electronically and can 
download a PDF of the consent forms for their records. Consent forms describe in detail 
the study intervention, study procedures, and risks (see below). Prior to the beginning of 
the trial, we will receive the IRB’s written approval for the protocol and the informed 
consent procedures and documents. 
10.1.1.2 
CONSENT PROCEDURES AND DOCUMENTATION 
Because this study involves no in-person visits, all consenting will occur electronically. 
There will be two consent forms: one describing the screening survey and one 
describing all other study procedures. Consent forms will be written at an eighth grade 
education level, use lay language, and will provide the following information: 
background and purpose of the study, scope and length of participation, randomization 
procedure, study procedures, follow-up assessments, legal and ethical limits to 
confidentiality, clinical interview audio and videotaping procedures, risks, benefits, 
alternatives, ability to discontinue participation, privacy and confidentiality, 
compensation, and whom to contact with questions. Women will be assured that their 
decision to participate or decline participation in the study will have no effect on their 
current or future receipt of healthcare services at UCSF or affiliated clinics. Women will 
be instructed to contact study staff with any questions, and will be able to download a 
copy of the consent forms for their records. For both consent forms, women will have 
the option to decline participation, consider their decision further, or provide their 
electronic signature to consent to participation. The orientation session provides another 
opportunity to engage participants in the informed consent process. In this session, 
study staff will meet by Zoom or phone to discuss the importance of the study question, 
the required commitments, what to expect if randomized to MBSR+PS or TAU, the 
rationale for random assignment, the consequences of attrition bias, and will answer 

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any questions that participants have.41 All consent forms will be approved by the UCSF 
IRB prior to study commencement. 
10.1.2 
STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the suspending or terminating party to study 
participants, Dr. Felder, funding agency, and regulatory authorities. If the study is 
prematurely terminated or suspended, the Principal Investigator (Dr. Felder) will 
promptly inform study participants, the Institutional Review Board (IRB), and National 
Center for Complementary and Integrative Health and will provide the reason(s) for the 
termination or suspension. Study participants will be contacted, as applicable, and be 
informed of changes to study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited 
to: 
• Determination of unexpected, significant, or unacceptable risk to participants 
• Demonstration of efficacy that would warrant stopping    
• Insufficient compliance of study staff to the protocol (i.e., significant protocol 
violations) 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
The study may resume once concerns about safety, protocol compliance, and data 
quality are addressed, and satisfy the NCCIH, IRB, or other relevant regulatory or 
oversight bodies (OHRP, DSMB). 
10.1.3 
CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the participating 
investigators, their staff, the Independent Monitoring Committee, and the sponsor and 
funding agency. This confidentiality is extended to the data being collected as part of 
this study. Data that could be used to identify a specific study participant will be held in 
strict confidence within the research team. No personally-identifiable information from 
the study will be released to any unauthorized third party without prior written approval 
of the sponsor/funding agency.  
Participants will be instructed to complete all research activities in as private a setting as 
possible (e.g., in a private room at home). 

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The Independent Monitoring Committee, authorized representatives of NCCIH, 
representatives of the Institutional Review Board (IRB) and regulatory agencies may 
inspect all documents and records required to be maintained by the investigator for the 
participants in this study. The clinical study site will permit access to such records. 
The study participant’s contact information will be securely stored for internal use during 
the study. At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by the reviewing IRB, Institutional policies, or 
sponsor/funding agency requirements. 
Study participant research data will be collected and stored on online survey platforms 
Qualtrics and REDCap, and stored on Box, a collaborative cloud-based collaboration 
tool. Individual participants and their research data will be identified by a unique study 
identification number. The study data entry and study management systems will be 
secured and password protected. At the end of the study, all study databases will be de-
identified and archived. 
It is NIH policy that the results and accomplishments of the activities that it funds should 
be made available to the public (see https://grants.nih.gov/policy/sharing.htm). The PI 
will ensure all mechanisms used to share data will include proper plans and safeguards 
for the protection of privacy, confidentiality, and security for data dissemination and 
reuse (e.g., all data will be thoroughly de-identified and will not be traceable to a specific 
study participant). Plans for archiving and long-term preservation of the data will be 
implemented, as appropriate.  
One limit to confidentiality is if a woman indicates she is at imminent risk to harming 
herself. If a participant endorses the self-harm item of the PHQ-9, a pop-up will 
immediately appear with instructions to call 911 or go to the nearest emergency room 
for a life-threatening emergency. Additionally, email triggers will immediately notify study 
staff, who will call to conduct a risk assessment using the Columbia-Suicide Severity 
Rating Scale (C-SSRS). At the beginning of the C-SSRS assessment, study staff will 
ask the participant for her current location. Study staff will provide psychological 
referrals for low to medium risk. For immediate risk, the study staff will direct the 
participant to the nearest emergency room and/or to call 911. If the participant declines, 
the study staff will call the participant’s local emergency services number, which will be 
recorded in the participant tracking database at enrollment. Study staff will immediately 
notify co-mentor Dr. Krystal, a psychiatrist with experience working with depressed and 
suicidal individuals, anytime a participant endorses suicidality on the PHQ-9. He will 
provide further supervision as deemed necessary and will determine whether additional 
follow-up assessment is indicated. Principal Investigator Dr. Felder, a licensed clinical 
psychologist with experience working with depressed perinatal women, will be a back-
up if Dr. Krystal is unavailable.  
This study does not require the use of a Certificate of Confidentiality. 
10.1.4 
FUTURE USE OF STORED SPECIMENS AND DATA  

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Data collected for this study will be stored on a cloud-based collaboration tool that uses 
access controls and encryption, and is safe for storing protected health information. 
Access will be limited to the PI and trained, authorized study staff. After the study is 
completed, the de-identified, archived data will be transmitted to and stored at the Dryad 
data repository for use by other researchers including those outside of the study. We 
will receive a permanent DOI for our data through Dryad, and we will meet NCCIH and 
publisher requirements for data sharing. Permission to transmit data to Dryad will be 
included in the informed consent. 
10.1.5 
KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator 
Medical Monitor 
(Medical)  
Medical Monitor 
(Psychiatric) 
Jennifer Felder, PhD, 
Assistant Professor and 
Principal Investigator 
Rick Hecht, MD, 
Professor and Co-
Investigator 
Andrew Krystal, MD, 
Professor and Co-
Investigator 
University of California, San 
Francisco 
University of California, 
San Francisco 
University of California, San 
Francisco 
Jennifer.Felder@ucsf.edu 
Rick.hecht@ucsf.edu 
Andrew.krystal@ucsf.edu 
 
Independent Monitoring 
Committee Member 
Independent Monitoring 
Committee Member 
Independent Monitoring 
Committee Member 
Norah Simpson, PhD, 
Clinical Associate Professor 
Jane Kim, PhD, Clinical 
Assistant Professor 
Judith Balk, MD 
Stanford University 
Stanford University 
Self-employed 
nsimpson@stanford.edu 
janepkim@stanford.edu 
judy_balk@icloud.com 
 
10.1.6 
SAFETY OVERSIGHT 
Safety oversight will be under the direction of an Independent Monitoring Committee 
(IMC) composed of individuals with the appropriate expertise, including sleep during 
pregnancy, biostatistics, and obstetrics and gynecology. Members of the IMC will be 
independent from the study conduct and free of conflict of interest. The IMC will meet at 
least semiannually to assess safety and efficacy data from each arm of the study. The 
IMC will operate under the rules of an approved charter that will be written and reviewed 
at the organizational meeting of the IMC. At this time, each data element that the IMC 

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needs to assess will be clearly defined. The IMC will provide its input to the National 
Institutes of Health staff. 
10.1.7 
CLINICAL MONITORING 
N/A 
10.1.8 
QUALITY ASSURANCE AND QUALITY CONTROL 
Quality control (QC) procedures will be implemented as follows: 
• Informed consent: Study staff will review both the documentation of the 
consenting process as well as a percentage of the completed consent 
documents. This review will evaluate compliance with GCP, accuracy, and 
completeness. Feedback will be provided to the study team to ensure proper 
consenting procedures are followed.  
• Follow-up measures: Self-report questionnaires will be designed to only accept 
valid responses. In real time and as close to data collection as possible, study 
staff will check each submitted self-report measure to identify and correct any 
potential issues (e.g., participant indicated on sleep diary that she went to sleep 
at 10:00 AM instead of 10:00 PM). Clinical research coordinators will make 
multiple attempts to contact participants to complete follow-up measures.  
• Intervention fidelity: Consistent delivery of the study interventions will be 
monitored throughout the intervention phase of the study. Procedures for 
ensuring fidelity of intervention delivery are described in Section 6.2.1, 
Interventionist Training and Tracking.  
• Protocol deviations: The study team will review and document protocol 
deviations on an ongoing basis and will implement corrective actions when the 
quantity or nature of deviations are deemed to be at a level of concern. 
Should independent monitoring become necessary, the PI will provide direct access to 
all trial related sites, source data/documents, and reports for the purpose of monitoring 
and auditing by the sponsor/funding agency, and inspection by local and regulatory 
authorities. 
10.1.9 
DATA HANDLING AND RECORD KEEPING  
10.1.9.1 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection will be the responsibility of study staff under the supervision of the 
principal investigator. The investigator will be responsible for ensuring the accuracy, 
completeness, legibility, and timeliness of the data reported. 
All data, including adverse events and use of non-study treatments, will be collected 
electronically using Qualtrics or REDCap. Each of these platforms encrypts all data, is 
HIPAA-compliant, and protects against data loss. Once downloaded, electronic data will 

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be stored on a cloud-based collaboration tool that uses access controls and encryption, 
and is safe for storing protected health information. Access will be limited to the PI and 
trained, authorized study staff.  
 
10.1.9.2 
STUDY RECORDS RETENTION  
Per University of California policy regarding IRB and academic research records, study 
documents will be retained for a minimum of 10 years after the end of the calendar year 
in which the research is completed. 
10.1.10 
PROTOCOL DEVIATIONS   
In accordance with UCSF IRB policy, this protocol defines protocol violations as 
changes in the conduct of an IRB-approved research protocol that are under the 
investigator’s control and made without prior IRB approval. Incidents are any 
problematic or unanticipated events that are not protocol violations and that may 
adversely impact on the study participants or the conduct of the study. 
Major (reportable) protocol violations are any unapproved changes in the research 
study design and/or procedures that are within the investigator’s control and not in 
accordance with the IRB-approved protocol that may affect the participant's rights, 
safety or well-being, or the completeness, accuracy and reliability of the study data. All 
major violations will be reported to the IRB. 
Major violations including, but not limited to incorrect intervention given, enrollment of 
ineligible participant, key safety procedure not done or done outside window, will be 
reported within 10 working days of awareness. 
Immediate protocol changes to protect participant safety will be reported within 10 
working days of occurrence. 
Major incidents including, but not limited to problem with consent or recruitment 
process, significant complaint or concern, lapse in study approval, loss of adequate 
resources, potential breach of confidentiality of confidentiality, will be reported within 48 
hours of awareness if they represent potential breaches of privacy or confidentiality. 
Other Major Incidents will be reported within 10 working days of awareness.  
Minor protocol violations (also known as protocol deviations) are any unapproved 
changes in the research study design and/or procedures that are within the 
investigator’s control and not in accordance with the IRB-approved protocol that do not 
have a major impact on either the participant’s rights, safety or well-being, or the 
completeness, accuracy and reliability of the study data. Minor protocol violations will 
not be reported to the IRB, but will be documented in the study files. 
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY  
This study will be conducted in accordance with the following publication and data 
sharing policies and regulations: 

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• National Institutes of Health (NIH) Public Access Policy, which ensures that the 
public has access to the published results of NIH funded research. It requires 
scientists to submit final peer-reviewed journal manuscripts that arise from NIH 
funds to the digital archive PubMed Central upon acceptance for publication. 
• This study will comply with the NIH Data Sharing Policy and Policy on the 
Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials 
Registration and Results Information Submission rule. As such, this trial will be 
registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish 
results in peer-reviewed journals.   
• After the study is completed, the de-identified, archived data will be transmitted to 
and stored at the Dryad data repository for use by other researchers including 
those outside of the study. 
10.1.12 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. 
Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. 
Furthermore, persons who have a perceived conflict of interest will be required to have 
such conflicts managed in a way that is appropriate to their participation in the design 
and conduct of this trial. Conflicts of interest will be reported in the IRB application, all 
financial interest disclosures will be kept current with the UCSF Conflict of Interest 
Program office, and we will disclose any financial or proprietary interests in the consent 
form.  
10.2 ADDITIONAL CONSIDERATIONS 
N/A 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
AE 
Adverse Event 
CBT-I 
Cognitive Behavioral Therapy for Insomnia 
CFR 
Code of Federal Regulations 
COVID-19 
Coronavirus Disease 2019 
C-SSRS 
Columbia-Suicide Severity Rating Scale 
CTSI PRP 
Clinical and Translational Science Institute Participant Recruitment 
Program 
DOI 
Digital Object Identifier 

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DSMB 
Data Safety Monitoring Board 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act  
ICH 
International Council on Harmonisation  
IMC 
Independent Monitoring Committee 
IRB 
Institutional Review Board 
ITT 
Intention-To-Treat 
MBCP 
Mindfulness-Based Childbirth and Parenting 
MBSR+PS 
Mindfulness-Based Stress Reduction + Prenatal Sleep Supplement 
MBSR 
Mindfulness-Based Stress Reduction 
MBTI 
Mindfulness-Based Therapy for Insomnia 
MOP 
Manual of Procedures 
MRN 
Medical Record Number 
NCT 
National Clinical Trial 
NCCIH 
National Center for Complementary and Integrative Health 
NIH  
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PDF 
Portable Document Format 
PHQ-9 
Patient Health Questionnaire-9 
PI 
Principal Investigator 
PROMIS 
Patient-Reported Outcomes Measurement Information System 
PSQI 
Pittsburgh Sleep Quality Index 
QC 
Quality Control 
RCT 
Randomized Clinical Trial 
REDCap 
Research Electronic Data Capture 
SAE 
Serious Adverse Event 

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10.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the 
protocol, including a description of the change and rationale. A Summary of Changes 
table for the current amendment is located in the Protocol Title Page.  
Version 
Date 
Description of Change  
Brief Rationale 
V2 
4/21/21 
Revise intervention to be 
mindfulness-based stress 
reduction plus prenatal sleep 
sessions 
To pilot test an 
intervention that is 
maximally potent and that 
will fit into the existing 
delivery system. 
V3 
11/8/21 
5. Include MBSR classes that 
are offered at locations in 
addition to UCSF Osher 
Center 
6. Add recruitment sources 
7. Remove Epworth 
Sleepiness Scale 
8. Increase the gestational 
age range from 12-28 to 8-
28. 
 
5. A significant challenge 
is that the UCSF Osher 
Center does not offer 
MBSR frequently, and 
the classes fill up 
quickly. Currently, the 
number of eligible 
RISE Study 
participants exceeds 
the available spots in 
the Osher MBSR class. 
Additionally, we have 
had otherwise eligible 
study participants who 
were unable to 
participate because 
they were not available 
at the particular time of 
the Osher MBSR class 
SAP 
Statistical Analysis Plan 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
TAU 
Treatment as Usual 
UCSF 
University of California, San Francisco 
UP 
Unanticipated Problem 
US 
United States 

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6. To enable rapid 
identification of eligible 
participants and to 
maximize likelihood 
that we can achieve 
our anticipated accrual 
rate. We are having a 
lower yield from our 
Facebook ads 
compared to our 
previous studies. We 
are adding recruitment 
sources that we found 
helpful in previous 
studies, such as 
parenting listservs and 
social media posts 
7. Initially we planned to 
use the Epworth to 
screen for narcolepsy. 
The Epworth has 
excluded 10% of 
respondents on our 
screener. Narcolepsy 
has a base rate of 
0.05%. Thus, it is 
highly implausible that 
10% of respondents 
had narcolepsy. 
Instead we believe the 
Epworth is identifying 
people with normative 
pregnancy-related 
sleepiness. 
Additionally, this 
measure is redundant 
with an item that 
assesses whether 
participants have been 
diagnosed with 
narcolepsy 
8. We have had several 
potential participants 
who are experiencing 
significant sleep 
disruption, are 

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interested in 
participating, but are 
less than 12 weeks 
pregnant (and will be 
too far along in their 
pregnancy for the next 
available MBSR 
course). This wider 
gestational age range 
is similar to our 
previous research, in 
which we evaluated 
digital CBT for prenatal 
insomnia, and enrolled 
participants at any 
point in pregnancy up 
until 28 weeks 
 
 
 
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