Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05610527 |
| Other study ID # |
IRB_00160085 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 1, 2024 |
| Est. completion date |
March 1, 2027 |
Study information
| Verified date |
March 2024 |
| Source |
University of Utah |
| Contact |
Amy Orr |
| Phone |
801-213-2774 |
| Email |
amy.orr[@]hsc.utah.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Of the 1.8 million females with inflammatory bowel diseases (IBD) in the US, over half of
those who are premenopausal suffer from cyclical menstrual-related IBD symptoms, regardless
of how well their disease is controlled. Despite the significant impact that cyclical IBD
symptoms, such as abdominal pain, diarrhea, and fatigue have on quality of life, evidence
about how to alleviate these symptoms is lacking. In other chronic conditions which are
hormonally influenced, such as epilepsy, hormonal contraception may be used to favorably
impact disease-related symptoms associated with menses and improve quality of life. In our
previous cross-sectional study, 47% of the levonorgestrel intrauterine device users and 19%
of combination oral contraceptive users reported improvement in their cyclical IBD symptom.
All hormonal methods may plausibly improve symptoms, but prospective, rigorous data
evaluating their efficacy for this purpose are lacking. In order to design a future
comparative effectiveness trial on the effect of hormonal contraceptive methods on
menstrual-related IBD symptoms, we propose this pilot prospective cohort study of 200 females
with IBD: 100 naturally cycling and 100 hormonal contraception users. We will gain essential
knowledge on IBD-specific influences on contraceptive method selection, willingness to be
randomized to methods, the ability of IBD patient reported outcome (PRO) instruments to
differentiate between non-menstrual and menstrual-related IBD symptoms, and assess the
potential role of inflammatory markers as outcome measures in future trials. We will recruit
participants from the University of Utah IBD Center and clinics, other Utah gastroenterology
providers, and through social media ads. Total study commitment will be ~12 weeks. Study
activities will include daily and weekly text message surveys, as well as blood draws and
fecal samples for inflammatory markers in a subset of participants which are commonly used
for IBD management. Our aims include: (1) To identify preferences and reasons for
contraceptive method selection (or non-use) and willingness to participate in a randomized
controlled trial, to inform feasibility of a future trial, (2) To obtain estimates of means
and standard deviations for the validated Crohn's Disease and Ulcerative Colitis PRO
Instruments by menstrual timing in naturally-cycling participants and between bleeding and
non-bleeding days in hormonal contraception users, and (3) To assess correlation between
inflammatory marker changes (fecal calprotectin & high sensitivity C-reactive protein),
menstrual timing or bleeding/non-bleeding days, and IBD PRO responses, in a subset of 30% of
Aim 1 participants. This pilot will inform a future trial design to define non-contraceptive
benefits of hormonal contraception on cyclical IBD symptoms. This line of inquiry will allow
for an adjuvant approach for IBD symptom management that is sex-specific and addresses both
concerns for hormonal triggers and the need for highly-effective contraception for those who
desire it.
Description:
Aim 1. Identify preferences and reasons for contraceptive method selection (or non-use) and
willingness to participate in a future randomized controlled trial in 200 participants with
IBD (100 naturally cycling and 100 hormonal contraception users). Our a priori cut off
requires ≥ 75% of participants accepting randomization.
Hypothesis: The majority of participants will accept randomization if they may switch methods
if not satisfied.
Aim 2. Obtain estimates of means and standard deviations for the validated Crohn's Disease
and Ulcerative Colitis PRO Instruments across the menstrual cycle (menses, ovulation,
pre-menstrual) in the naturally-cycling participants and between bleeding and non-bleeding
days in the hormonal contraception users.
Hypothesis: IBD PRO instruments will reliably reflect IBD symptom changes related to
menstrual phases.
Aim 3. Assess the correlation between inflammatory marker changes (fecal calprotectin & high
sensitivity C-reactive protein), menstrual timing and/or bleeding days, and IBD PRO responses
in a subset of 30% of Aim 1 participants (30 naturally cycling and 30 hormonal contraception
users).
Hypothesis: Changes in inflammatory markers will be correlated with menstrual phases and IBD
PRO responses.
Study Design: A pilot prospective cohort study of 200 women with IBD (100 naturally cycling
and 100 hormonal contraception users).
Recruitment. We will recruit via four different sources: 1. With the support of the
co-investigators who are IBD subspecialists at the University of Utah (Drs. Flynn and
Johnson), we will send recruitment emails to their patients who meet inclusion criteria via
the Epic patient portal (MyChart). 2. We will post fliers regarding the study in the
gastroenterology, primary care, and women's health clinics across University of Utah sites.
3. We will send recruitment materials to other non-university gastroenterology sites in Utah.
4. We will advertise via social media nationally with a link to a University of Utah Research
Enterprise Data Capture (REDCap) survey to assess eligibility and provide contact information
for study coordinators to connect for a phone screen.
AIM 1 Sample Size: This is a pilot study designed to collect baseline data to inform future
trials and not powered to assess statistical differences between study groups. We plan to
recruit 200 participants in an IBD setting who represent common contraceptive method choices
and compare hormonal method users to non-users regarding preferences in method selection. The
sample size will also give a breadth of perspectives on willingness to be randomized to
different hormonal methods under variable study conditions and designs to influence a future
trial. Our sample size takes into consideration feasibility for recruitment given our
recruitment timeline, as well as sample size recommendations for pilot clinical trials.
Participant procedures: Total study engagement is 12 weeks. Enrollment processes. Study staff
will complete a phone screening, discuss study procedures, and if they meet inclusion
criteria, either email the potential participant the consent and enrollment survey for
completion via REDCap or schedule an in-person enrollment visit if participating in the Aim 3
sub study to allow for inflammatory marker collection. The screening phone call will include
request of documentation confirming IBD diagnosis and screening questions regarding timing of
IBD diagnosis, current disease activity, prior endoscopy and surgery dates, current and prior
treatments, and any hospitalizations. These responses and documentation of diagnoses will be
reviewed for eligibility by the IBD subspecialists before consent and enrollment is
completed.
Survey content. The enrollment survey will assess sociodemographic and reproductive
characteristics, IBD history as above, menstrual cycle timing and symptoms including bleeding
characteristics and pain scores, sexual satisfaction surveys, baseline IBD symptom PRO
instruments, menstrual-related IBD symptoms, prior and current contraceptive experiences, and
preferences regarding contraceptive methods. Using an adapted 7-item Attitudes to Randomized
Trials Questionnaire, participants will be presented with hypothetical RCT scenarios to
assess willingness to be randomized based on different methods, different study designs (e.g.
participant preference arm), options to switch methods, and then query regarding reasoning if
not willing to be randomized.
Study Arms: The "naturally-cycling" cohort will include participants who are not using any
form of hormonal contraception and meet inclusion criteria with regular menses. This may
include non-hormonal method users, including abstinence, copper IUD, self or partner
permanent contraception, barrier methods, or fertility awareness methods. The hormonal
contraception user cohort includes the most common hormonal contraceptive options (COC, LNG
IUD, ENG implant). The hormonal contraceptive method must have been initiated prior to study
enrollment, thus the method choice made outside of this study is not an intervention. If a
participant initiates, stops, or switches methods during the study, they will be analyzed in
the assigned cohort at enrollment, as changes in hormonal methods may not result in
consistent bleeding profiles or resumption of natural cycles for weeks to months.
Follow-up. While the aim 1 outcome assessment occurs with the enrollment survey, all
participants will be followed for Aim 2 and a subset for Aim 3 for 12 weeks from the time of
enrollment. Participants will receive compensation for time with each completed study
activity.
Analyses. The goal of Aim 1 is to define the characteristics of the IBD study population and
determine a point estimate of the proportion of participants willing to be randomized to one
of three contraceptive methods under each scenario characteristics. A 95% confidence interval
around this estimate will describe its variability. The 7-item Attitudes to Randomized Trials
Questionnaire30 is not scored in sum, but each item adds characteristics related to the
proposed study design that are reported via descriptive statistics as positive or negative
attributes influencing randomization willingness. We will report contraceptive method
preferences and IBD-specific reasons for method selection (and non-use of hormonal methods)
via descriptive statistics, inferential analysis exploring relationships between respondent
characteristics and method preferences, adjusting for participant characteristics as well as
thematic findings from free text response options. For free text responses, we will use
frequency distributions as well as Latent Dirichlet Allocation, a topic modeling technique to
identify common themes and patterns in the responses. We will also conduct comparative
analysis to compare IBD-specific reasons for method selection or non-use of hormonal methods
across different demographics and disease characteristics. While the enrollment survey and
all daily and weekly PRO instruments will be administered electronically to all participants,
we anticipate that certain significant differences may also exist between participants who
agree to enroll in Aim 3 and those who do not. This may be due to their willingness to come
for in-person lab assessments and engagement with the study team. We will thus perform
sensitivity analyses to determine, for each of these groups, the proportion willing to be
randomized and to assess contraceptive method preferences. Similarly, we will perform
sensitivity analyses for both those who switch, discontinue or initiate a contraceptive
method and for those who are abstinent and may be using hormonal contraception for
non-contraceptive purposes only compared to those who need contraception for pregnancy
prevention.
AIM 2 Sample size. All study participants recruited in Aim 1 will be included in this aim. We
anticipate a 5% attrition in survey completion over 12 weeks.
Procedures. Participants will receive electronic survey links to assess IBD-related and
menstrual-related symptoms, QOL measures, sexual activity and health changes across menstrual
cycles and bleeding and non-bleeding days in the hormonal contraception users over 12 weeks.
Via REDCap, we will send automated reminders and deliver links for data completion through
text messages to the participant's mobile phone or device. Participant responses
automatically upload from the phone or device to REDCap.
Daily surveys. Daily surveys will begin the day of enrollment and continue for 12 weeks. The
survey questions include either the CD or UC PRO instrument depending upon diagnosis. The
daily IBD PRO instruments include modules on signs and symptoms, systemic symptoms, and
coping strategies with a total of 17 questions (6 minutes) for the CD PRO and 20 questions (7
minutes) for the UC PRO. We will also query chronic pelvic pain severity, vaginal bleeding
and amount, and if bleeding, menstrual-related pain and severity (4 follow-up questions if
bleeding).
Weekly Surveys. The weekly surveys will begin on day of enrollment and continue every week
for 12 weeks (13 total with the enrollment survey). These longer surveys will include the
daily questions plus the IBD PRO modules on daily life impact with 9 questions (3 minutes)
and emotional impact with 8 questions (3 minutes). Participants will complete a Likert scale
on how bothersome IBD symptoms have been in the past week, and report any sexual activity
with assessment of dyspareunia, additional treatments for IBD or menstrual symptoms, and any
changes to health history.
Analyses. This aim will assess changes in IBD PRO responses over subsequent menstrual cycles
and between bleeding and non-bleeding days for hormonal contraceptive users. The UC PRO and
CD PRO instrument modules will all be scored based on guidelines for instrument use. Report
of bothersome IBD symptoms, chronic pelvic pain, dysmenorrhea, and dyspareunia will be on a
Likert scale from 0-10. Any other reported changes in health, treatments or concerns will be
reported by frequency and cycle timing. We will compare variations in these means across
menstrual cycle timing using linear regression and compare means in symptom scores between
cohorts using paired t-tests.
AIM 3 Sample size. We will enroll 30% of each cohort from Aim 1 in this sub study for a total
of 60 participants.
Procedures. Potential participants eligible for Aim 1 who are willing and able to come to a
study enrollment visit and 12 subsequent lab visits at the University of Utah will be offered
participation in this Aim 3 sub study. For those interested, their enrollment will occur
in-person, rather than virtually in order to initiate the inflammatory marker collection. At
the enrollment visit, the research staff review the same electronic consents used for
participants in Aim 1 and 2 and prompt completion of the enrollment survey using the
University of Utah's secure, web-based REDCap system. The enrollment visit will also include
urine pregnancy testing, lab testing (complete blood count, hsCRP, ferritin, and albumin) and
they will receive a kit to collect fecal calprotectin from a home stool sample and return it
at the 1-week blood draw. Lab assessments of inflammatory markers will occur at varying
intervals. WBC, ferritin and albumin will be assessed at baseline screening visit and again
monthly (4 total). The hsCRP will be measured at baseline and then occur weekly (13 total).
Fecal calprotectin (from 1st morning stool) will be measured at baseline (sample collected at
1-week blood draw after enrollment) then monthly for 12 weeks (4 total). The blood draws and
fecal calprotectin assessments that occur after the single in-person enrollment visit can be
completed at local University labs throughout the region.
Analyses. We will compare the proportion of participants with hsCRP and fecal calprotectin
levels within a 'normal' range by cohort (naturally cycling vs hormonal contraception users)
using chi square. We will compare variations in means across menstrual cycles using mixed
effects models. We will look for difference in inflammatory marker levels across IBD PRO
responses and specific modules by including these PROs as covariates in our regression
models, and will include a random intercept in our models for participants in order to
account for variations in individual baseline marker levels.
