Clinical trial NCT03493126
Conditions: Vaginal Atrophy
Keywords: postpartum, local estrogen
Sponsor: Ohio State University
Start date: 2018-10-15; Completion date: 2020-09-01
Enrollment: 59 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Pilot randomized, placebo-controlled trial of nulliparous postpartum women with a perineal laceration following a term vaginal delivery comparing vulvovaginal atrophy symptoms between women using vaginal estrogen in the postpartum period with those using placebo.

Detailed description:
The overall goal of this study is to determine whether there are benefits to use of low-dose vaginal estrogen in the postpartum period. Dyspareunia and vaginal/perineal pain are well-known sequelae after vaginal delivery. However, the contribution of postpartum vaginal atrophy to these issues is largely unknown. Although the relationship between lactation, relative estrogen deprivation, and vulvovaginal atrophy has been established, there is a paucity of data regarding on the prevalence of vulvovaginal atrophy symptoms in the postpartum period. Additionally, although the benefits of vaginal estrogen in postmenopausal atrophy are well-established, the benefits in the postpartum period are unknown.

Arms: arm 1: Estrace: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum. arm 2: Placebo: pea sized amount 2 times per week from week 1 postpartum to 3 months postpartum.
Interventions: intervention 1: Estradiol intervention 2: Placebo
Intervention descriptions: intervention 1: 17β-estradiol vaginal cream intervention 2: Compounded placebo cream

Protocol documents:
Prot_SAP_000.pdf: 
 
Title: A Pilot Randomized Controlled Trial of Vaginal Estrogen on Postpartum Atrophy, Perineal Pain, 
and Sexual Function 
 
Date of Document 1/27/2018 
Date of IRB Approval 1/30/2018 
 
 


 
 
 
Principal Investigator(s):  
Pamela Escobar Smith, MD 
The Ohio State University Wexner Medical Center 
Pamelaescobar.Smith@osumc.edu 
 
Catherine O. Hudson, MD 
The Ohio State University Wexner Medical Center 
Catherine.Hudson@osumc.edu 
 
 
Co-Investigators:  
 
Erinn M. Hade, Ph.D. 
The Ohio State University Wexner Medical Center 
Erinn.Hade@osumc.edu 
 
Andrew F. Hundley, MD 
The Ohio State University Wexner Medical Center 
Andrew.hundley@osumc.edu 
 
Courtney Lynch, Ph.D., MPH 
The Ohio State University Wexner Medical Center 
Courtney.Lynch@osumc.edu 
 
Eric McLaughlin, M.S. 
The Ohio State University Wexner Medical Center 
Eric.McLaughlin@osumc.edu 
 
Silpa Nekkanti, MD 
The Ohio State University Wexner Medical Center 
Silpa.Nekkanti@osumc.edu 
 
Lopa K. Pandya, MD 
The Ohio State University Wexner Medical Center 
Lopa.pandya@osumc.edu 
 
 
 


ABSTRACT (157) 
 
Dyspareunia and vaginal/perineal pain are well-known sequelae after vaginal delivery.  However, the 
contribution of postpartum vaginal atrophy to these issues is largely unknown. Although the relationship 
between lactation, relative estrogen deprivation, and vulvovaginal atrophy has been established, there is a 
paucity of data regarding the prevalence of vulvovaginal symptoms in the postpartum period and treatment 
options. We plan to evaluate the feasibility and preliminary efficacy of local estrogen on postpartum 
genitourinary symptoms by performing a pilot randomized, placebo-controlled trial of nulliparous postpartum 
women with a perineal laceration following a term vaginal delivery. The primary aim of this study is to compare 
vulvovaginal atrophy symptoms between women using vaginal estrogen in the postpartum period with those 
using placebo.  Secondary aims of this study include assessment and comparison of vaginal/perineal pain, 
quality of life, incontinence and sexual function between the two groups as well as treatment satisfaction. 
Patients will report adverse reactions in all groups for evaluation of safety. 
 
SPECIFIC AIMS 
The overall goal of this study is to determine whether there are benefits to use of low-dose vaginal estrogen in 
the postpartum period.  Dyspareunia and vaginal/perineal pain are well-known sequelae after vaginal delivery.  
However, the contribution of postpartum vaginal atrophy to these issues is largely unknown.  Although the 
relationship between lactation, relative estrogen deprivation, and vulvovaginal atrophy has been established, 
there is a paucity of data regarding on the prevalence of vulvovaginal atrophy symptoms in the postpartum 
period. Additionally, although the benefits of vaginal estrogen in postmenopausal atrophy are well-established, 
the benefits in the postpartum period are unknown.   
 
Recent studies investigating postpartum dyspareunia and pelvic pain have largely gathered data from patient 
questionnaires, timing of return to coitus, and measures of pelvic floor muscle function including vaginal resting 
pressure and pelvic floor muscle strength.1 Only few studies have commented on the prevalence of postpartum 
vulvovaginal atrophy. Wisniewski and Wilkinson described a 17.2% prevalence of vulvovaginal atrophy in a 
prospective study of women at 4 weeks postpartum.2 The authors noted dyspareunia was present in 80% of 
atrophic patients attempting coitus as compared to 12.9% of controls with mode of delivery comparable in both 
groups. While the study was not designed to determine efficacy, the authors described a therapeutic response 
with application of conjugated estrogen vaginal cream. Vaginal estrogen has been utilized in clinical practice 
for patients undergoing atrophic changes postpartum with pain and dyspareunia despite lack of data on its 
efficacy. Vaginal estrogen has also been used to treat persistent granulation present in vaginal repairs. 
Although anecdotally this treatment is beneficial, there are very few descriptions of its use in the postpartum 
period and no published comparative trials.  It remains unclear whether the use of vaginal estrogen in the 
postpartum period is truly beneficial.  Questions remaining to be answered include:  Does vaginal estrogen 
improve postpartum vaginal atrophy?  Does it improve healing of obstetrical lacerations?  If so, does it also 
improve pain, incontinence and sexual function during this period?   We seek to perform a randomized 
placebo-controlled trial to evaluate the effect of local vaginal estrogen in the postpartum period to answer these 
questions.    
 
Specific Aim 1:  To evaluate the feasibility (recruitment, retention and adherence to therapy) and 
preliminary efficacy of local estrogen on vulvovaginal atrophy in the postpartum period.  
 
Hypothesis:  Use of low-dose vaginal estrogen in the postpartum period will decrease postpartum 
vaginal atrophy and associated symptoms. 
 
We chose a validated measurement of vulvovaginal symptoms as our primary measure of vulvar atrophy. The 
Vaginal Vulvar Assessment Scale tools will be utilized during an exam at 6 weeks and 12 weeks. The tool also 
has a scale for physical exam findings associated with atrophy that will be recorded as well.  Given most 
postpartum visits are scheduled at four to six weeks following a vaginal delivery for an uncomplicated 


pregnancy and acute surgical wounds usually complete healing within two to four weeks, six weeks was 
deemed appropriate timing for vulvar assessment. The primary outcome for the study is Vulvar Assessment 
Scale (VuAS) at 6 weeks. Vaginal pH and maturation index will be obtained at follow up postpartum visits to 
further assess atrophy. Vaginal pH will be obtained in a standardized manner by swabbing indicator strips with 
pH range of 4.0 to 7.5 against the distal posterior vagina and interpreted by the examiner. Vaginal maturation 
will also be obtained via vaginal smears at the introitus and sent for quantitative assessment.  Presence of 
granulation tissue and visible healing abnormalities such as suture line disruption, visible sutures, abscess, 
hematoma, and need for reoperation will be noted.  
 
Specific Aim 2: To estimate the effect of local vaginal estrogen in the postpartum period on perineal 
pain, quality of life, and sexual function.  
 
Hypothesis:  Use of low-dose vaginal estrogen in the postpartum period will improve vaginal and 
perineal pain, quality of life measures and sexual function. 
 
These will be assessed using validated questionnaires consisting of a visual analog scale for pain (VAS), 
Edinburgh Postnatal Depression Scale (EPDS), the Urinary Distress Inventory-6 (UDI-6), the Fecal 
Incontinence Severity Index for bowel symptoms (FISI), and the Female Sexual Function Index (FSFI). These 
questionnaires will be completed on day of randomization and postpartum visits at 6 weeks and 12 weeks. 
 
Specific Aim 3:  To compare patient satisfaction, ease of product use, likelihood of continued use, and 
rates of adverse events for the vaginal estrogen and placebo groups.  
 
Hypothesis:  Use of low-dose vaginal estrogen in the postpartum period will have a higher treatment 
satisfaction rate when compared with placebo.  The rate of adverse events between the groups will be 
similarly minimal. 
 
We will use a Likert scale to assess patient satisfaction, ease of product use, comfort, and likelihood of 
continued use. We will monitor for adverse events related or possibly related to local estrogen.  All local 
estrogen and non-local estrogen adverse events will be recorded. 
 
Impact: There is limited knowledge of dyspareunia and perineal pain postpartum and the role of vulvar and 
vaginal atrophy. Increased efforts to measure and improve postpartum sexual functioning can impact a 
substantial number of women suffering from these oftentimes lengthy symptoms. Given the psychological 
burden a patient can endure from pelvic floor pain, it is important investigate treatment options for women with 
perineal trauma in the postpartum period.  
 
RESEARCH STRATEGY 
 
A.SIGNIFICANCE 
The postpartum period is a challenging time that requires a balance of physical, social, and psychological 
changes. It is characterized by such challenges as lack of sleep, fatigue, pain, breastfeeding, depression, 
stress, lack of sexual desire and urinary incontinence.3 The majority of women in the United States do not 
interact with a health care provider after discharge until the first postpartum visit 4 to 6 weeks following 
delivery. Because of this, many postpartum complaints may not be addressed in the limited time available.  
The postpartum period is not well defined but considered to last between 4 to 6 weeks following delivery during 
which anatomical and physiological changes return to the non-pregnant state.4 This time frame likely 
represents historical traditions, as studies have demonstrated peripartum effects are present months after 
delivery.5 Evidence-based studies of optimal maternal postpartum management are lacking and clinical 
recommendations are often based on expert opinion and observational studies. 6 Recent data on urinary and 


sexual functioning postpartum have been important in investigating some of the health domains significant to 
women during this period.7 
 
The prevalence of postpartum sexual dysfunction in women has been noted to be 41-83% in the first 2 to 3 
months after delivery.8,9 In addition to obstetrical factors, fatigue, stress, partner, body image, breastfeeding, 
and hormonal changes contribute to sexual functioning postpartum. 10 In a secondary analysis of 2,748 
primiparous women, specific risk factors for dyspareunia identified at 6 months were breastfeeding, perineal 
pain, fatigue and stress11 Women breastfeeding at 6 months were 2.89 times more likely (95% confidence 
interval [CI] 2.33-3.59, P<.001) to report dyspareunia compared to non-breastfeeding women. These results 
underscore the potential impact of lactation on vulvovaginal atrophy and sexual functioning postpartum. 
Furthermore, 32.5% of participants reporting perineal pain at 1 month were 2.45 times more likely (95% CI 
1.93-3.10, P<.001) to report dyspareunia at 6 months. Increased efforts to measure and improve postpartum 
sexual functioning can impact a substantial number of women suffering from these oftentimes persistent 
symptoms. While studies have aimed at improving the understanding of postpartum maternal morbidities as 
well as severity and persistence of symptoms contributing to sexual function, few studies have evaluated 
treatment options.  
 
Clinical use of vaginal estrogen and associated research have been limited mostly to the genitourinary 
syndrome of menopause, described as the symptoms and signs of the genital system resulting from decreased 
estrogen levels, including vaginal or vulvar dryness, burning, dyspareunia, or dysuria, urgency or frequency.12 
A 2014 systematic review of 44 studies of vaginal estrogen for women with genitourinary syndrome of 
menopause described improved dryness, dyspareunia, urinary urgency, frequency, stress urinary 
incontinence, and urgency urinary incontinence compared with placebo.13 In addition, the authors found that 
vaginal estrogen also decreased urinary tract infection rates. While there is minimal research regarding the use 
of vaginal estrogen in the postpartum period, it is commonly done in obstetric practice.  Because vulvovaginal 
atrophy can be present in both menopausal and postpartum states, it is reasonable to assume that many of the 
benefits seen with vaginal estrogen use in menopausal women may translate to postpartum use as well. 
 
As a pilot intervention study for vulvovaginal symptoms in postpartum women with perineal injury, we seek to 
study the effects of local estrogen on postpartum vulvar symptoms utilizing validated scales and objective 
biomarkers. Ultimately, we anticipate this study will contribute to treatment of dyspareunia and vulvar atrophy. 
 
B.INNOVATION 
 
The mechanisms of estrogen deficiency and local estrogen on vulvar and vaginal tissue have been described 
previously. Local vaginal estrogen has been accepted for treatment vulvovaginal symptoms in postmenopausal 
patients. By applying local estrogen to postpartum patients with a similar physiological state of estrogen 
deficiency, we anticipate improvements in symptoms of vulvovaginal atrophy. In our pilot randomized 
controlled trial of a commonly used vaginal estrogen cream, we will gather initial rigorous evidence to evaluate 
if this treatment is appropriate for resolution of vulvar symptoms in the immediate postpartum period.  
 
C.APPROACHES 
C.1.Specific Aim 1: To evaluate the feasibility (recruitment, retention and adherence to therapy) and 
preliminary efficacy of local estrogen on vulvovaginal atrophy in the postpartum period 
 
Background, preliminary results and rationale 
In a 2014 systematic review of local estrogen use for genitourinary symptoms in postmenopausal women, no 
differences were found in efficacy or safety between different vaginal estrogen preparations at typical dose and 
frequencies for vaginal dryness, itching or burning, atrophy-related dyspareunia, dysuria, urgency, frequency, 
nocturia, and incontinence (Rahn et al). Estrogen vaginal delivery methods including cream, tablet, ovule, 
suppository or ring are typically influenced by cost, ease of application, and patient preference. Estradiol 


(Estrace®) cream will be utilized for the study given its extended use at the clinic sites. Participants will be 
given instructions for estradiol (Estrace®) cream at the initial clinical starting dose of 1g twice weekly. To our 
knowledge there has been no previous rigorous evaluation of local estrogen in the postpartum period. 
 
Research Design 
This is a pilot randomized, placebo-controlled trial at a single academic center to examine the feasibility of use 
and preliminary efficacy of local estrogen in women with perineal injury in the immediate postpartum period.   
We will be assessing symptoms and physical findings associated with vulvovaginal atrophy, perineal pain, 
quality of life, and sexual function at 6 weeks and 12 weeks. Prior to enrollment, all patients with a term 
pregnancy will have been admitted to Ohio State University Wexner Medical Center and will have undergone 
obstetrical care as provided by their primary care team for a vaginal delivery at term. Once the patient has 
been cleared for transfer to the postpartum unit, a member of the study team (study nurse or coordinator) will 
introduce the study and, if the patient agrees, will assess her for eligibility and enrollment prior to discharge. If 
the participant is eligible and agrees to participate, written consent will be obtained and she will be enrolled in 
the study.  
 
Inclusion criteria: females >18 years old with at least one prior prenatal care appointment affiliated with The 
Ohio State University Wexner Medical Center; nulliparous; 1-2 days status post   >37 weeks and 0 day vaginal 
delivery with at least a second degree perineal laceration; English-speaking and able to provide informed 
consent. 
 
Exclusion criteria: allergies to estradiol cream or its constituents; a current or previous diagnosis of estrogen-
dependent breast cancer; inability to complete questionnaires in English or comply with study protocol; and 
inability to apply vaginal cream independently.  
 
Randomization 
Randomization to either Estrace® cream for use 1g twice weekly or placebo cream for use 1g twice weekly will 
be implemented in the study's electronic data capture system, REDCap. Participants will be randomly allocated 
to the treatment arms in a 1:1 ratio. The randomization scheme will be stratified by degree of obstetrical 
laceration: 2nd degree laceration or 3rd/4th degree laceration. Third and fourth degree lacerations, referred to as 
obstetric anal sphincter injuries, are less frequent but more often associated with increased risk of fecal and 
urinary incontinence, pain, and sexual dysfunction, potentially impacting study outcomes. The allocation 
scheme will be balanced between treatment groups by permuted blocks of varying size.  The scheme will be 
developed by the study statisticians (Dr. Hade and Mr. McLaughlin) and will remain blinded to study PIs, 
treating physicians, and those collecting final outcome measures, and study staff where possible. 
 
The primary outcome will be a comparison of the clinical scores as assessed by the Vulvar Assessment 
Scale (VuAS) at 12 weeks postpartum in the vaginal estrogen and placebo groups. The VuAS has been 
utilized as a brief clinical measurement to identify vulvovaginal symptoms in patients with atrophic vaginitis and 
genitourinary symptoms of cancer survivors.14,15 The VuAS is a four-item measurement administered by a 
clinical provider that quantifies and rates the patient’s responses to questions of dryness, soreness, irritation 
and pain to external stimulation. Patients are asked whether they have experienced specific symptoms 
(“yes/no”) during the past 4 weeks and rate symptom severity (“none,” “mild,” ”moderate,” “severe”). The first 3 
items assess dryness, soreness, and irritation during routine activities excluding sexual intercourse and the 
fourth item assesses pain with external manual stimulation. An option for “no attempt” indicates a patient has 
not been sexually active within the past 4 weeks. The VuAS also contains a physical exam component that 
evaluates the external genitalia, including the labia minora, labia majora, clitoral hood, clitoris, and perineum. 
The administering physician can provide clarification as needed and a diagram can be used to educate 
patients regarding anatomy. Each item in the VuAS is scored from 0 (none) to 3 (severe) with composite 
scores calculated by taking the mean of the items when at least two of four items are not missing. 


Higher scores indicate worse symptoms. Considering the first three items focus on vulvar health as compared 
to sexual function specifically, two composite scores will exists for each group. The alternative score will only 
include a composite score of items 1 to 3 as patients may have missing scores if answering “no attempt” for 
item 4. The VuAS has been demonstrated to assess change in self-reported measurement of atrophic 
symptoms. In a randomized trial of estradiol vaginal tablets and hyaluronic acid sodium salt in symptomatic 
postmenopausal women with atrophic vaginitis, the VuAS noted a significant decrease in symptoms after an 8 -
week treatment course. In a validation study of VuAS as well as the Vaginal Assessment Scale (VAS) in 
cancer survivors, a strong correlation was observed between VAS dyspareunia and Female Sexual Function 
Index (FSFI) pain with intercourse. Additionally, increased severity of symptoms on VAS and VuAS were 
correlated with worse pain on exam, worse functioning on FSFI pain, lubrication, worse vulvar irritation, and 
worse total scores. The VAS tool is a secondary measure that will be scored at the same time points: 6 weeks 
and 12 weeks. In addition to the VuAS, a pelvic exam will be performed and will include obtaining vaginal pH 
and maturation index in a standardized manner as it is a validated measure of urogenital atrophy and vaginal 
health.16 Presence of granulation tissue and visible healing abnormalities such as suture line disruption, visible 
sutures, abscess, hematoma, and need for reoperation will be noted.  
 
Other patient characteristics to be collected will include baseline demographics and delivery 
characteristics, gathered from the patient’s electronic medical record including: age, race, past medical, 
surgical obstetric and gynecologic history, and delivery variables including infant birth weight at delivery, 
chorioamnionitis, duration of ruptured membranes, duration of second stage, operative delivery, degree of 
laceration, and plan for breastfeeding.  
 
Treatment administration 
Instructions will be given to patients at the time of their hospital admission following their delivery but prior to 
hospital discharge. Only Estrace® cream will be used to avoid influence of different types of estradiol products 
available. They will be asked to follow directions of cream application 1g twice weekly to simulate “real world 
use.” Participants in the vaginal estrogen protocol will be given instructions to administer Estrace® cream 1g 
as measured by plastic applicator calibrated to 1g increments to a maximum of 2g. The Estrace® cream will be 
placed intravaginally twice weekly manually. Refill tubes will be given at follow up visits. Participants will return 
to the office at 6 weeks and 12 weeks and evaluated by a Female Pelvic Medicine and Reconstructive Surgery 
specialist part of the research team. Participants in the placebo protocol will be given a vaginal cream 
alongside a plastic applicator calibrated to 1g increments with instructions to administer 1g intravaginally twice 
weekly. Refill tubes will be given at follow up visits. Participants will return to the office at 6 weeks and 12 
weeks and evaluated by a Female Pelvic Medicine and Reconstructive Surgery specialist part of the research 
team.  
 
Statistical Methods 
Sample size determination and recruitment 
Based on preliminary data, it is expected that approximately 560 nulliparous births with at least a 2nd degree 
laceration will be observed at the Wexner Medical Center from our generalist clinic in one year providing nearly 
50 potentially eligible births to screen each month. Recruitment is expected to last 4-6 months. Consistent with 
our goals to evaluate preliminary efficacy and the feasibility of recruiting, retaining and monitoring of patient 
adherence to therapy our study sample size is based on more lenient criteria than would be expected in a 
definitive randomized trial.  Very preliminary evidence for the primary endpoint, VuAS suggests that the 
average scores in those untreated would be on average 0.8 (sd=0.8) (Eaton et al).  We reasonably expect to 
be able to recruit and fund the treatment for up to 70 participants, randomized, 1:1.  Assuming 20% attrition 
of those initially randomized at the 6 week follow-up, 35 patients will complete their 6-week follow-up visit. We 
would have 80% power to reject the null hypothesis of equal means with 10% two-sided type I error for a 50% 
reduction in the VuAS score. This larger type I and II error rates are reasonable for a pilot efficacy evaluation.  
 
Analysis plan 


Demographic and baseline characteristics of all participants will be summarized and presented overall and by 
assigned treatment group. We would expect approximate balance of observed and unobserved participant 
characteristics between study groups. Any chance imbalance in characteristics known to be related to primary 
or secondary outcomes will be considered as adjustment variables in outcomes analyses.  Analysis of the 
primary outcome, VuAS at 6 weeks, will be compared regardless of treatment adherence or dose of 
intervention received (intent to treat analysis, (ITT).  Primary efficacy analysis comparing VuAS scores at 6 
weeks between the randomized groups will be estimated via linear regression, adjusting for stratification factor 
of laceration degree. Further analysis will consider adjustment for chance imbalances in key patient 
characteristics.  Secondary analyses will investigate the VuAS at later time points, through linear mixed models 
or linear generalized estimating equation models (GEE), accounting for correlation over time. Recruitment 
screening counts, refusal rates, and retention rates will be reported overall and by treatment group.  All 
statistical analysis will be performed using SAS or STATA. Data will be presented according to CONSORT 
2010 guidelines for randomized controlled trials. 
 
Data capture 
All study data will be collected using standardized electronic case report forms (CRF)s in REDCap. The study 
team (PIs and study statisticians) will develop CRFs for data capture for both patient reported and data 
abstracted from the medical record. Dr. Hade and Mr. McLaughlin will monitor all incoming data, with particular 
attention to: 1) enrollment and follow-up reports as entered into the database, 2) potential adverse events, and 
3) missing data (for complete visits and for particular items) or extreme values. Regular reporting to the study 
team will work to reconcile or report issues as needed and to monitor participant retention.  
 
Pitfalls and Solutions 
Study limitations include retention difficulties and compliance issues. Dropout will be minimized by telephone or 
text reminders one week prior to patients’ scheduled postpartum visit and attempts will be made to schedule 
study visits on same day of routine obstetrical postpartum visits for the first follow up visit. Eligible patients will 
also include only patients with a history regular prenatal care by an obstetrician with offices affiliated with the 
Wexner Medical Center. If participants are unable to attend their scheduled visit, a phone interview will be 
conducted to fill out questionnaires. In addition, patient adherence to twice weekly application in vaginal 
estrogen and placebo groups will be noted. Again text reminders will be used to encourage compliance.  
Patients will be asked about adherence at each follow up visits and reasons for discontinuation or deviation 
from instructions will be noted.  
 
Specific Aim 2: To estimate the effect of local vaginal estrogen in the postpartum period on perineal 
pain, quality of life, and sexual function. 
 
Background, preliminary results and rationale 
In order to effectively evaluate the impact of each group on perineal pain, quality of life, and sexual function in 
the early postpartum period, we will administer baseline and follow-up questionnaires.  Changes will be 
assessed using validated questionnaires consisting of a visual analog scale for pain (VAS) and Edinburgh 
Postnatal Depression Scale (EPDS).  Researchers in the field of Female Pelvic Medicine and Reconstructive 
Surgery have also created several validated questionnaires to assess these measures.  We will be able to 
objectively assess quality of life by using the following validated questionnaires: The Urinary Distress Inventory 
(UDI-6), the Fecal Incontinence Severity Index for bowel symptoms (FISI), and the Female Sexual Function 
Index (FSFI).  These questionnaires have consistently been used in landmarks trials in the assessment of 
female pelvic floor disorders.    
 
Research Design 
1.Perineal pain:  The VAS scale ranges from 0 to 100 with 100 indicating maximum pain. 
 


2.Quality of Life measures: The EPDS is a validated 10-question depression assessment for postpartum 
women, which includes anxiety symptoms and excludes constitutional symptoms associated with depression 
common in the postpartum period, such as changes in sleeping patterns. Each question is given a score of 0 to 
3 and a total score of at least 10 indicates minor or major depression at the time of the patient’s follow-up; The 
UDI-6 is a questionnaire that includes 6 items evaluating bother form urinary symptoms with higher scores 
indicating more bothersome symptoms; The FISI evaluates patient responses symptom severity to fecal 
incontinence with higher scores indicating more bothersome anal incontinence symptoms. 
 
3.Sexual function: The FSFI is a validated questionnaire to assess sexual function in six domains of sexual 
function, including desire, arousal, lubrication, orgasm, satisfaction, and pain over the 4 weeks prior to 
administration of questionnaire with lower scores indicating more sexual dysfunction. 
 
Questionnaires will be administered to all groups at baseline enrollment and clinic encounters at 6 
weeks and 12 weeks. See Fig 1. 
 
Statistical Analysis 
Similar to analyses proposed in Aim 1, secondary endpoints will be analyzed via generalized linear mixed 
models or linear generalized estimating equation models (GEE), adjusting for stratification factors and 
accounting for correlation over time. 
 
Anticipated results 
Assuming an improvement in perineal symptoms associated with vulvar atrophy with local estrogen use, 
patients will have a significant improvement in perineal pain, quality of life, and sexual function.   
 
Pitfalls and Solutions 
Again retention and compliance is a concern in the postpartum period.  Strategies including telephone and text 
reminders will be utilized.  If patients are unable to attend their follow-up visit, a study member will call the 
patient and record the patient’s responses.    
 
Specific Aim 3:  To compare patient satisfaction, ease of product use, likelihood of continued use, and 
rates of adverse events for the vaginal estrogen and placebo groups.  
 
Background, preliminary results and rationale 
In order to effectively evaluate the impact of each group on satisfaction and ease of product use and likelihood 
of continued use of vaginal estrogen and placebo group, we will administer global rating scales. Global ratings 
of satisfaction have previously been found to have acceptable validity for measuring outcomes in studies of 
treatment for urinary incontinence. 
 
Research Design 
1.  Satisfaction and ease of use:  These outcomes will be assessed with Likert scales collected via RedCap at 
weeks 6 and 12.  Satisfaction will be assessed using the patient satisfaction questionnaire, with responses of 
“completely,” “somewhat,” and “not at all,” in response to the question, “How satisfied were you with your 
progress with this treatment?” In a similar fashion, ease of usability will be scored be assessed on a score of 0, 
1, 2, 3, 4, 5, and 6, correlating to the following responses of “strongly disagree,” “disagree,” “slightly disagree,” 
neither agree nor disagree”, “slightly agree,” “agree,” “strongly agree” to the statement, “This product was easy 
to use.” 
  
2.  Likelihood of continued use: This will be assessed at the end of the study intervention with a 7-point Likert 
scale at weeks 6 and 12. This will be assessed on a score of 0, 1, 2, 3, 4, 5, and 6, correlating to the following 
responses of “strongly disagree,” “disagree,” “slightly disagree,” neither agree nor disagree”, “slightly agree,” 
“agree,” “strongly agree” to the statement, “I plan to continue using this product.” 


 
3.  Adverse events (AEs): Potential AEs of interest include vaginal pain attributed to cream placement, vaginal 
infection, wound separation, and urinary tract infection. Breast myalgia and breastfeeding practices will be 
noted. Participants will be instructed to call and report any/all adverse events to research personnel and clinical 
staff.  All AEs will be reported to the IRB of the institution at which the AE occurred, recorded in the research 
database and if needed the patient will be seen for a clinical assessment.  At each clinical/research visit the 
participant will be asked about any adverse events.  AEs will be reported with study outcomes. 
 
Questionnaires will be administered to vaginal estrogen and placebo groups at clinic encounters at 6 
weeks and 12 weeks. See Fig 1. 
 
Statistical Analysis 
Similar to analyses proposed in Aim 1, secondary endpoints will be analyzed via generalized linear mixed 
models or linear generalized estimating equation models (GEE), adjusting for stratification factors and 
accounting for correlation over time. 
 
Anticipated results 
Assuming an improvement in perineal symptoms associated with vulvar atrophy with local estrogen use, 
patients will have higher scores in satisfaction and likelihood of continued use compared to placebo group. 
Ease of use global rating will likely be similar in vaginal estrogen and placebo groups.  
 
Pitfalls and Solutions 
Again retention and compliance is a concern in the postpartum period.  Strategies including telephone and text 
reminders will be utilized.  If patients are unable to attend their follow-up visit, a study member will call the 
patient and record the patient’s responses.    
 
D.  RIGOR AND REPRODUCIBILITY 
All participants will be postpartum women with a perineal laceration following a vaginal delivery at Wexner 
Medical Center. Wexner Medical Center has approximately 5,000 deliveries per year.  It is a large, 
multidisciplinary academic medical center that delivers superior quality care to a diverse urban population of 
patients. Columbus,Ohio is the fifteenth largest city in the United States and is home to a population 
representing 134 nations and speaking 105 languages. In addition, The Ohio State University (OSU) Divisions 
of Obstetrics and Gynecology represents a diverse team of faculty, residents, and fellows dedicated towards 
improving women’s health through evidence-based care, research, and education. As an institution, OSU 
Wexner Medical Center has long been supportive of leadership in research and excellence in patient care.  
 
Estrace® cream is currently available for the treatment of genitourinary symptoms of menopause. We 
anticipate other clinicians will have similar results in their population.  
 
E.  HUMAN SUBJECTS 
The three main commercially available preparations for vaginal estrogen in the United States are cream, ring, 
and tablet. Vaginal creams include a 17β-estradiol vaginal cream and a conjugated estrogen cream. The use 
of the Estrace® cream or estradiol vaginal cream has FDA-approved for the treatment of vulvovaginal 
symptoms of atrophy due to menopause.  In regards to this study, Estrace® cream has not been FDA-
approved for the use of genitourinary symptoms of atrophy in postpartum women with perineal lacerations. 
However, vaginal estrogen has been utilized in clinical practice to improve vulvovaginal atrophy and wound 
healing postoperatively in vaginal reconstructive surgery and cases of mesh erosion and exposure. As 
compared to its alternatives, a 2014 systematic review of 44 studies of vaginal estrogen for women with 
genitourinary syndrome of menopause found various local estrogen preparations had similar efficacy and 
safety with extremely rare cases of hyperplasia and adenocarcinoma with up to 1 years of use in 
postmenopausal women. There were no cases of venous thromboembolism or breast cancer reported 


comparing vaginal estrogen with placebo. Studies demonstrate low-dose vaginal estrogen use does not result 
in sustained serum estrogen levels exceeding normal menopausal range. 17 Studies have also not 
demonstrated an increased risk of cancer recurrence among women currently undergoing treatment for breast 
cancer or prior history of breast cancer who use vaginal estrogen for genitourinary symptoms.18 However, 
given vaginal estrogen is considered second-line treatment for urogenital symptoms of menopause in patients 
with breast cancer or prior history of breast cancer, these patients will be excluded from our study. T opical 
vaginal estrogen cream has demonstrated low levels of systemic absorption with no detectable effect on 
coagulation proteins or incidence of venous thromboembolism. Local estrogens bypass the gastrointestinal 
conversion of estradiol to estrone with less increase in triglyceride levels, clotting factors, and globulins.19 
 
We do not anticipate an impact on lactation supply or practices given the lack of sustained increased serum 
estradiol levels in prior studies. Furthermore, in a systematic review of estrogen-containing contraceptives 
among breastfeeding women, the authors note an inconsistent impact of estrogen-containing contraceptives 
on breastfeeding when initiated prior to 6 weeks postpartum. In fact, the authors highlight a fair quality study 
demonstrating no impact on supplementation or breastfeeding continuation of estrogen-containing 
contraceptives when compared to progesterone-only pills.20  
 
This study will only include female participants who are at least 18 years old.  We will not limit the study based 
on race, unless unable to provide consent in English, as all patients who will undergo a vaginal delivery with 
subsequent perineal laceration at Wexner Medical Center will be taken into consideration for eligibility 
 
IRB Approval 
This study is currently approved by the Ohio State University Wexner Medical Center IRB.  
 
F. EVALUATION CRITERIA AND PROGRESS 
Study Visits 
The participants will be randomly assigned to estrogen cream or placebo for 12. The primary outcome is 
difference in tissue quality via the VuAS at 6 weeks between patients randomly assigned to vaginal estrogen 
versus placebo cream. Secondary outcomes will compare the effect of local estrogen on: VuAS at 6 and 12 
weeks, the VAS at 6 weeks and 12 weeks, perineal pain, quality of life, and sexual function as measured by 
validated questionnaires in the field of Female Pelvic Medicine and Reconstructive Surgery at 6 weeks and 12 
weeks. Patient satisfaction and treatment continuation will be measured at each follow up visit. (Table 2: Study 
Assessment by Visit).  
 
G.POINT OF CONTACT 
Pamela Smith, MD 
Clinical Fellow, Female Pelvic Medicine and Reconstructive Surgery 
Department of Obstetrics and Gynecology 
The Ohio State University 
Columbus, OH 43210 
Phone: 614-293-4302 
Fax: 614-293-5877 
Email: Pamelaescobar.smtih@osumc.edu 
 
 
 
 
Aims 
Evaluation 
Baseline 
Week 6 
Week 12 
  
Consent 
X 
  
  
  
Demographics 
X 
  
  
Aim 1  
Pelvic Exam 
  
X 
X 


  
VuAS 
  
X 
X 
 
VAS 
 
X 
X 
  
Vaginal pH 
  
X 
X 
 
MI 
 
X 
X 
Aim 2 
EPDS 
  
X 
X 
  
UDI-6 
  
X 
X 
  
FISI 
  
X 
X 
  
FSFI 
  
X 
X 
Aim 3 
Patient satisfaction 
  
X 
X 
  
Continued use 
  
X 
X 
 
 
STUDY TIMELINE 
Month 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
IRB approval 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Recruitment 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Data Collection 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Data analysis 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Preparation of results 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Study Closeout 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
1 Tennfjord Mk, Hilde G, Staer-Jensen J, Ellstrom Ength M, Bo K. Dyspareunia and pelvic floor muscle function 
before and during pregnancy and after childbirth. Int Urogynecol J. 2014 Sep;25(9):1227-35.  
 
2 Wisniewski PM, Wilskinson EG. Postpartum vaginal atrophy. Am J Obstet Gynecol. 1991 
Oct;165(4Pt2):1249-54.  
 
3 Haran C, van Driel M, Mitchell BL, Brodribb WE. Clinical guidelines for postpartum women and infants in 
primary care—a systematic review. BMC Pregnancy Childbirth 2014;14:51 
 
4 Committee Opinion No 666: Optimizing Postpartum Care. Obstet Gynecol. 2016 Jun;127(6):e187-92 
 
5 Sutton KS, Boyer SC, Goldﬁnger C, Ezer P, Pukall CF. To lube or not to lube: Experiences and perceptions 
of lubricant use in women with and without dyspareunia. J Sex Med 2012;9:240–50. 
 
6 Martin A, Horowitz C, Balbierz A, Howell EA. Views of women and clinicians on postpartum preparation and 
recovery. Matern Child Health J 2014;18:707–13. 
 
                                                             


                                                                                                                                                                                                                                  
7 De Souza A, Dwyer PL, Charity M, Thomas E, Ferreira CH, Schierlitz L. The effects of mode delivery on 
postpartum sexual function: a prospective study. BJOG 2015 Sep;122(10):1410-8. 
 
8 Barrett G, Pendry E, Peacock J, et al. Women’s sexual health after childbirth. BJOG 2000;107:186-195.  
 
9 Leeman LM, Rogers RG. Sex after childbirth: postpartum sexual function. Obstet Gynecol 2012;119:647-655. 
 
10 Hipp LE, Kane Low L, Van Anders SM. Exploring women’s postpartum sexuality: social, psychological, 
relational, and birthrelated contextual factors. J Sex Med 2012;9:2330-2341.  
 
11 Alligood-Percoco NR, Kjerulff KH, Repke. Risk Factors for Dysparunia After First Childbirth. Obstet Gynecol. 
2016 Sep;128(3):512-8.  
 
12 Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Vulvar and vaginal atrophy in postmenopausal women: 
findings from the REVIVE (REal Women’s Views of Treatment Options for Menopausal Vaginal ChangEs) 
survey. JSex Med. 2013 Jul; 10(7):1790-9. 
 
13 Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward FM, Meriwether KV, Olivera CK, Abed H, Balk EM, 
Murphy M; Society of Gynecologic Surgeons Systematic Review Group. Vaginal estrogen for genitourinary 
syndrome of menopause: a systematic review. Obstet Gynecol. 2014 Dec;124(6): 1147-56.  
 
14 Ekin M, Yas ̧ar L, Savan K, et al. The comparison of hyaluronic acid vaginal tablets with estradiol vaginal 
tablets in the treatment of atrophic vaginitis: a randomized controlled trial. Arch Gynecol Obstet 2011;283:539-
543. 
 
15 Eaton AA, Baser RE, Seidel B, Stabile C, Canty JP, Goldfrank DJ, Carter J. Validation of Clinical Tools for 
Vaginal and Vulvar Symptom Assessment in Cancer Patients and Survivors. J Sex Med. 2017 Jan;14(1):144-
151.  
 
16 Brizzolara S, Killeen J, Severino R. Vaginal pH and parabasal cells in postmenopausal women. Obstet 
Gynecol 1999;94(5):700Y703. 
 
17 Rigg LA, Hermann H, Yen SS. Absorption of estrogens from vaginal creams. N Engl J Med 1978;298:195–7.  
 
18 Ponzone R, Biglia N, Jacomuzzi ME, Maggiorotto F, Mariani L, Sismondi P. Vaginal oestrogen therapy after 
breast cancer: is it safe? Eur J Cancer 2005;41:2673–81 
 
19 Ballagh SA. Vaginal hormone therapy for urogenital and menopausal symptoms. Semin Reprod Med 
2005;23:126–40 
 
20 Tepper NK, Phillips SJ, Kapp N, Gaffield ME, Curtis KM. Combined hormonal contraceptive use among 
women: an updated systematic review. Contraception. 2016 Sep:94(3):262-74 

ICF_001.pdf: 
CONSENT & 
AUTHORIZATION 
 
 
 
IRB Protocol Number: 
2018H006 
IRB Approval date:  01/30/2018 
Version:  01/27/2018 
 
 
Page 1 of 9 
 
 
 
 
Title: A Pilot Randomized Controlled Trial of Vaginal Estrogen on Postpartum Atrophy, 
Perineal Pain, and Sexual Function 
 
Date of Document 1/27/2018 
Date of IRB Approval 1/30/2018 


CONSENT & 
AUTHORIZATION 
 
 
 
IRB Protocol Number: 
2018H006 
IRB Approval date:  01/30/2018 
Version:  01/27/2018 
 
 
Page 2 of 9 
 
 
 
 
The Ohio State University Combined Consent to Participate in 
Research and HIPAA Research Authorization 
 
 
Study Title: 
A Pilot Randomized Controlled Trial on Vaginal Estrogen on 
Postpartum Atrophy, Perineal Pain, and Sexual Function 
Principal Investigator: 
Catherine Hudson, MD 
Sponsor:  
The Ohio State University Wexner Medical Center 
 
 This is a consent form for research participation.  It contains important information 
about this study and what to expect if you decide to participate.  Please consider the 
information carefully. Feel free to discuss the study with your friends and family and 
to ask questions before making your decision whether or not to participate. 
 Your participation is voluntary.  You may refuse to participate in this study.  If you 
decide to take part in the study, you may leave the study at any time.  No matter what 
decision you make, there will be no penalty to you and you will not lose any of your 
usual benefits.  Your decision will not affect your future relationship with The Ohio 
State University.  If you are a student or employee at Ohio State, your decision will 
not affect your grades or employment status. 
 You may or may not benefit as a result of participating in this study.  Also, as 
explained below, your participation may result in unintended or harmful effects for 
you that may be minor or may be serious depending on the nature of the research. 
 You will be provided with any new information that develops during the study 
that may affect your decision whether or not to continue to participate.  If you 
decide to participate, you will be asked to sign this form and will receive a copy of the 
form.  You are being asked to consider participating in this study for the reasons 
explained below.   
 
1.   Why is this study being done? 
You are being asked to take part in this study because you have experienced a perineal 
tear after your vaginal delivery at The Ohio State University. The perineum is the area by 
the urinary, vaginal, and rectal openings. The vulva includes the female external 
reproductive organs. 
 
The goal of this study is to test the safety, feasibility, and effectiveness of using vaginal 
estrogen cream Estrace®, to treat vulvar symptoms, including dryness, itchiness, perineal 
pain and pain with intercourse, in postpartum patients. You will receive either a vaginal 
estrogen cream or a placebo cream. A placebo cream contains inactive ingredients. The 
vaginal estrogen cream has been proven to improve dryness, lubrication, and elasticity in 


CONSENT & 
AUTHORIZATION 
 
 
 
IRB Protocol Number: 
2018H006 
IRB Approval date:  01/30/2018 
Version:  01/27/2018 
 
 
Page 3 of 9 
 
 
postmenopausal patients. The study will try to evaluate if similar results are seen in 
postpartum patients with a perineal tear.  
 
2.   How many people will take part in this study? 
Approximately 112 subjects will take part in this study at The Ohio State University. 
 
3.   What will happen if I take part in this study? 
Prior to taking part in this study you will be asked to review and sign this consent form. 
 
Screening/Registration 
After you have signed this consent form, you will: 
 be asked for some demographic information 
 be randomly selected by chance to receive either Estrace® vaginal estrogen cream 
or placebo cream during a 6-month long study. You will be given instructions to 
place 1gram of the cream, “a pea-sized amount,” on the perineum nightly for two 
times a week. We will schedule your next visit prior to discharge from the hospital 
 30 minute follow up at a clinic at 6 weeks, 3 months, and 6 months postpartum 
 be asked to fill out a diary describing rates of sexual activity and cream use prior 
to clinic visits  
 
Clinic Encounters 
You will be asked to return to the clinic for three clinic visits: 6 weeks, 3 months, and 6 
months postpartum. At each of these three visits, you will: 
 
 Complete 5 questionnaires asking about genital symptoms, pain, and sexual 
function as well as your satisfaction with the treatment. You will be given as much 
time as you need to complete these questionnaires. The health care provider will 
also ask you about any problems that you may be having with the cream. 
 Receive a pelvic exam to monitor tissue quality and wound healing.  You will be 
asked about any pain or discomfort you experience during the process, and your 
answers noted in a questionnaire. 
 
      You will receive a refill of your medication at your 3 month visit 
 
End of Study 
After your 6 month clinic visit, you will not be scheduled for any further visits. You will 
be notified if you received Estrace® vaginal estrogen cream or placebo cream during your 
treatment protocol. You will receive a 15 minute follow up telephone call from one of our 
study coordinators up to 1 year after you have completed participation in the study. They 
may ask you questions regarding genital symptoms, pain, and sexual function 
 
4.   How long will I be in the study? 
You will be in the study for approximately 1 year. 
 


CONSENT & 
AUTHORIZATION 
 
 
 
IRB Protocol Number: 
2018H006 
IRB Approval date:  01/30/2018 
Version:  01/27/2018 
 
 
Page 4 of 9 
 
 
 
5. Can I stop being in the study? 
You may leave the study at any time.  If you decide to stop participating in the study, 
there will be no penalty to you, and you will not lose any benefits to which you are 
otherwise entitled.  Your decision will not affect your future relationship with The Ohio 
State University.  
 
 
6.   What risks, side effects or discomforts can I expect from being in the study? 
You may have side effects while on this study. Everyone taking part in the study will be 
watched carefully for any side effects. However, the study team does not know all the side 
effects that may happen. Expected adverse events are light vaginal bleeding, vaginal pain, 
mild allergic reaction or breast tenderness. There is minimal risk associated with vaginal 
estrogen and placebo cream but you may potentially experience vaginal discomfort or an 
allergic reaction with use of the product. Symptoms of light vaginal bleeding, vaginal pain 
or breast tenderness are expected during the normal postpartum time. Unexpected or 
serious adverse events include serious allergic reaction, venous thromboembolism (blood 
clots), neoplasia (cancer), acute kidney injury, stoke, death or other. As prior literature 
indicates, however, these events are extremely low.  
 
You should talk to your study doctor about any side effects that you have while 
taking part in the study. 
 
Risk of Discomfort During Questionnaires 
You will be asked to answer questions about your body (including your vagina) and your 
sexual activity. It is possible that answering these questions may make you feel 
uncomfortable. You will be given as much time as you need to complete these 
questionnaires. You do not have to answer any question on the questionnaires that make 
you feel uncomfortable.  
 
Risk of Breach of Confidentiality 
As part of this study you are at risk for a breach in confidentiality of your protected health 
information (PHI). We will protect your PHI by storing your data in a secure database and 
coding your PHI however you are still at risk for a breach in confidentiality. 
 
 
7.   What benefits can I expect from being in the study? 
There may or may not be any direct benefit to you for participating in this study. If the 
intervention improves your symptoms, it might help with management of vaginal atrophy 
and sexual function. It is hoped that the information gathered during this study will help 
research to improve the sexual function and quality of life for future postpartum patients.  
 
 
8.   What other choices do I have if I do not take part in the study? 


CONSENT & 
AUTHORIZATION 
 
 
 
IRB Protocol Number: 
2018H006 
IRB Approval date:  01/30/2018 
Version:  01/27/2018 
 
 
Page 5 of 9 
 
 
You may choose not to participate without penalty or loss of benefits to which you are 
otherwise entitled. Your provider will discuss appropriate options available to you 
regarding your condition. Available options will be dependent on your health and severity 
of your condition and can vary from patient to patient.  
 
 
9. What are the costs of taking part in this study? 
There will be no direct cost for you to participate in the study. There is no standard 
treatment for vulvar or perineal symptoms after a vaginal delivery. You will not be billed 
for the treatment that you receive. You will not be billed for any study-related visits.  
 
 
10. Will I be paid for taking part in this study? 
You will receive $10 compensation after your 6 week visit. You will be enrolled in a 
raffle to win a $100 gift card if you complete the 6 month visit. You have 1 in 112 chance 
of winning the $100 gift card at the end of the study period.  
 
 
11. What happens if I am injured because I took part in this study? 
If you suffer an injury from participating in this study, you should notify the researcher or 
study doctor immediately, who will determine if you should obtain medical treatment at 
The Ohio State University Wexner Medical Center.   
 
The cost for this treatment will be billed to you or your medical or hospital insurance. The 
Ohio State University has no funds set aside for the payment of health care expenses for 
this study.  
 
 
12. What are my rights if I take part in this study? 
If you choose to participate in the study, you may discontinue participation at any time 
without penalty or loss of benefits.  By signing this form, you do not give up any personal 
legal rights you may have as a participant in this study. 
 
You will be provided with any new information that develops during the course of the 
research that may affect your decision whether or not to continue participation in the 
study. 
 
You may refuse to participate in this study without penalty or loss of benefits to which 
you are otherwise entitled. 
 
An Institutional Review Board responsible for human subjects research at The Ohio State 
University reviewed this research project and found it to be acceptable, according to 
applicable state and federal regulations and University policies designed to protect the 
rights and welfare of participants in research. 
 


CONSENT & 
AUTHORIZATION 
 
 
 
IRB Protocol Number: 
2018H006 
IRB Approval date:  01/30/2018 
Version:  01/27/2018 
 
 
Page 6 of 9 
 
 
 
13. Will my study-related information be kept confidential? 
Efforts will be made to keep your study-related information confidential.  However, there 
may be circumstances where this information must be released.  For example, personal 
information regarding your participation in this study may be disclosed if required by state 
law.   
 
Also, your records may be reviewed by the following groups (as applicable to the 
research): 
 
Office for Human Research Protections or other federal, state, or international 
regulatory agencies; 
 
U.S. Food and Drug Administration; 
 
The Ohio State University Institutional Review Board or Office of Responsible 
Research Practices; 
 
The sponsor supporting the study, their agents or study monitors; and 
 
Your insurance company (if charges are billed to insurance). 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. law.  This website will not include information that can identify you.  At 
most, the website will include a summary of the results.  You can search the website at 
any time.  
 
 
14. HIPAA AUTHORIZATION TO USE AND DISCLOSE INFORMATION FOR 
      RESEARCH PURPOSES  
 
I. What information may be used and given to others? 
 Past and present medical records; 
 Research records; 
 Records about phone calls made as part of this research; 
 Records about your study visits; 
 Information that includes personal identifiers, such as your name, or a number 
associated with you as an individual; 
 Information gathered for this research about: 
Physical exams 
Laboratory, x-ray, and other test results 
Diaries and questionnaires 
 Records about the study device.  
 
II. Who may use and give out information about you? 
Researchers and study staff.   
 
III. Who might get this information? 
 The sponsor of this research.  “Sponsor” means any persons or companies that are: 


CONSENT & 
AUTHORIZATION 
 
 
 
IRB Protocol Number: 
2018H006 
IRB Approval date:  01/30/2018 
Version:  01/27/2018 
 
 
Page 7 of 9 
 
 
 working for or with the sponsor; or  
 owned by the sponsor. 
 Authorized Ohio State University staff not involved in the study may be aware that 
you are participating in a research study and have access to your information; 
 If this study is related to your medical care, your study-related information may be 
placed in your permanent hospital, clinic or physician’s office record; 
 
IV.  Your information may be given to:  
 The U.S. Food and Drug Administration (FDA), Department of Health and Human 
Services (DHHS) agencies, and other federal and state entities; 
 Governmental agencies in other countries; 
 Governmental agencies to whom certain diseases (reportable diseases) must be 
reported; and  
 The Ohio State University units involved in managing and approving the research 
study including the Office of Research and the Office of Responsible Research 
Practices. 
 
V. Why will this information be used and/or given to others? 
 To do the research;  
 To study the results; and  
 To make sure that the research was done right.   
 
VI. When will my permission end? 
There is no date at which your permission ends. Your information will be used 
indefinitely. This is because the information used and created during the study may be 
analyzed for many years, and it is not possible to know when this will be complete. 
 
VII. May I withdraw or revoke (cancel) my permission? 
Yes. Your authorization will be good for the time period indicated above unless you 
change your mind and revoke it in writing. You may withdraw or take away your 
permission to use and disclose your health information at any time. You do this by 
sending written notice to the researchers. If you withdraw your permission, you will not 
be able to stay in this study. When you withdraw your permission, no new health 
information identifying you will be gathered after that date. Information that has already 
been gathered may still be used and given to others. 
 
VIII. What if I decide not to give permission to use and give out my health 
information? 
Then you will not be able to be in this research study and receive research-related 
treatment.  However, if you are being treated as a patient here, you will still be able to 
receive care. 
 
IX. Is my health information protected after it has been given to others? 


CONSENT & 
AUTHORIZATION 
 
 
 
IRB Protocol Number: 
2018H006 
IRB Approval date:  01/30/2018 
Version:  01/27/2018 
 
 
Page 8 of 9 
 
 
There is a risk that your information will be given to others without your permission. Any 
information that is shared may no longer be protected by federal privacy rules. 
 
X. May I review or copy my information? 
Signing this authorization also means that you may not be able to see or copy your study-
related information until the study is completed.   
 
 
15. Who can answer my questions about the study? 
For questions, concerns, or complaints about the study, or if you feel you have been 
harmed as a result of study participation, you may contact Catherine Hudson, MD or 
Pamela Escobar Smith, MD at 614-293-4643. 
 
 
 
 
For questions related to your privacy rights under HIPAA or related to this research 
authorization, please contact the HIPAA Privacy Officer in the College of Medicine at 
614-292-2856 or by mail at: 
 
 
 
HIPAA Privacy Officer 
 
 
 
Suite E2140 
 
 
 
600 Ackerman Road 
 
 
 
Columbus, OH, 43202 
 
For questions about your rights as a participant in this study or to discuss other study-
related concerns or complaints with someone who is not part of the research team, you 
may contact Ms. Sandra Meadows in the Office of Responsible Research Practices at 1-
800-678-6251. 
 
If you are injured as a result of participating in this study or for questions about a study-
related injury, you may contact Catherine Hudson, MD or Pamela Escobar Smith, MD 
at 614-293-4643. 
 
 


CONSENT & 
AUTHORIZATION 
 
 
 
IRB Protocol Number: 
2018H006 
IRB Approval date:  01/30/2018 
Version:  01/27/2018 
 
 
Page 9 of 9 
 
 
Signing the consent form 
I have read (or someone has read to me) this form and I am aware that I am being asked to 
participate in a research study.  I have had the opportunity to ask questions and have had them 
answered to my satisfaction.  I voluntarily agree to participate in this study.  
 
I am not giving up any legal rights by signing this form.  I will be given a copy of this 
combined consent and HIPAA research authorization form. 
 
 
 
 
 
Printed name of subject 
 
Signature of subject 
 
 
 
 
 
AM/PM 
 
 
Date and time 
 
 
 
 
 
 
 
 
 
Printed name of person authorized to consent for subject 
(when applicable) 
 
Signature of person authorized to consent for subject  
(when applicable) 
 
 
 
 
 
AM/PM 
Relationship to the subject 
 
Date and time 
 
 
 
 
Investigator/Research Staff 
 
I have explained the research to the participant or his/her representative before requesting the 
signature(s) above.  There are no blanks in this document.  A copy of this form has been given 
to the participant or his/her representative. 
 
 
 
 
 
Printed name of person obtaining consent 
 
Signature of person obtaining consent 
 
 
 
 
 
AM/PM 
 
 
Date and time 
 
 
Witness(es) - May be left blank if not required by the IRB 
 
 
 
 
 
Printed name of witness 
 
Signature of witness 
 
 
 
 
 
AM/PM 
 
 
Date and time 
 
 
 
 
 
Printed name of witness 
 
Signature of witness 
 
 
 
 
 
 
AM/PM 
 
 
Date and time