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Hormonal Influences on Inflammatory Bowel Diseases

Studies

Study First Submitted Date 2022-10-13
Study First Posted Date 2022-11-09
Last Update Posted Date 2023-06-08
Start Month Year March 1, 2024
Primary Completion Month Year March 1, 2026
Verification Month Year June 2023
Verification Date 2023-06-30
Last Update Posted Date 2023-06-08

Detailed Descriptions

Sequence: 20566429
Description Aim 1. To determine acceptability of randomization to the ENG contraceptive implant or 52mg-LNG IUD and in those who decline, acceptability of participation in a participant-preference arm. Hypothesis: The majority of participants will accept randomization if they may switch methods if not satisfied. Aim 2. To obtain estimates of means and standard deviations in established IBD symptom scales (Harvey Bradshaw and partial Mayo) and IBD quality of life measures across the phases of two menstrual cycles and then for 6 months after contraceptive method initiation. Hypothesis: IBD symptom scale domains and total scores as well as quality of life measures will reliably reflect IBD symptom changes after contraceptive method initiation. Aim 3. To obtain preliminary estimates of inflammatory marker (fecal calprotectin and high sensitivity C-reactive protein) variation across menstrual phases and pre- and post- contraceptive initiation. Hypothesis: Variations that occur as a result of menstrual phase and IBD activity will decrease after contraceptive initiation. Study Design: A pilot prospective randomized trial with a patient-preference arm for those who decline randomization to assess acceptability of randomization to the ENG implant or LNG IUD in people with IBD and menstrual-related IBD symptoms. Participant recruitment: The investigators will recruit via four different sources: 1. The investigators will send recruitment emails to the University of Utah IBD Center patients who meet inclusion criteria via the Epic patient portal (MyChart). 2. The investigators will post fliers regarding the study in the gastroenterology, primary care, and women's health clinics across University of Utah sites. 3. The investigators will send recruitment materials to other non-university gastroenterology sites in Utah and request flier use in their clinics. 4. The investigators will advertise via targeted social media within the University of Utah catchment area 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. Sample Size: This pilot study is designed to collect baseline data to inform future trials and not powered to assess statistical differences between study groups. The investigators plan to recruit 40 participants to assess recruitment feasibility, while allowing for a large enough sample to assess acceptability of randomization, adherence to the protocol and survey completion requirements. Our sample size takes into consideration feasibility for recruitment given our recruitment timeline, as well as sample size recommendations for pilot clinical trials. The investigators anticipate at least 30 participants will find randomization acceptable with up to 10 in a participant-preference arm. Randomization scheme and concealment: The REDCap system will generate the randomization sequence with varied blocks (four and six): 1. ENG implant and 2. LNG IUD. No treatment concealment will occur for participants or providers due to differences in devices and inability to conceal either those inserting them, but statisticians not will be aware of treatment assignment, only study arm 1 or 2. Participant procedures: Total study engagement is ~8 months with ~2 months of natural menstrual cycles followed by contraceptive method placement and 6 months of follow-up. Phone screening visit: Subjects will be screened for eligibility and interest in the study followed by review of clinical documentation confirming IBD diagnosis. In-person screening visit: Each subject will have the study explained and, if participation is desired, informed consent documents will be signed prior to any study procedures. The screening visit will include urine pregnancy testing, physical examination, lab testing (complete blood count, hsCRP, ferritin, and they will receive kit to collect fecal calprotectin from home stool sample and return at 1 week blood draw). Participants will complete an enrollment survey to assess sociodemographic and reproductive characteristics, IBD history including current and prior treatments, menstrual cycle timing and symptoms including bleeding characteristics and pain scores, sexual satisfaction surveys, baseline IBD symptom surveys and quality of life measures, menstrual-related IBD symptoms, acceptability of randomization, method desired and reasoning if not willing to be randomized, and prior contraceptive experiences. Daily surveys. These short surveys will begin the day following the screening visit and continue through 6 months following LARC method insertion (~8 months total study engagement). They will query the patient-reported questions for the IBD symptom scale depending on diagnosis (Harvey Bradshaw Index for Crohn's vs. partial Mayo Score) which assess stool pattern, rectal bleeding, abdominal pain, and well-being. The investigators will also query chronic pelvic pain severity, vaginal bleeding and amount, and if bleeding, menstrual-related pain and severity. Weekly Surveys. These longer surveys will include the daily questions plus the Short Form IBD QOL index, a Likert scale on how bothersome IBD symptoms have been in the past week, sexual activity with assessment of dyspareunia and the Contraceptive Sexual Acceptability survey, additional treatments for IBD or menstrual symptoms, and any changes to health history. Lab assessments of inflammatory markers will occur at varying intervals. WBC, ferritin and albumin will be assessed at baseline screening visit and again at the exit visit 6 months post-method insertion. The hsCRP will be measured at baseline and then occur weekly until contraceptive device insertion and then monthly until the 6-month exit visit. Fecal calprotectin (from 1st morning stool) will be measured at baseline (sample collected at 1-week blood draw after enrollment), at LARC initiation, then monthly for 6 months. The hsCRP and fecal calprotectin assessments that occur outside of scheduled clinic visits can be drawn/dropped off at local University labs throughout the region. In-person contraceptive placement visit: The participant will notify the research staff when their 2nd menstrual cycle after screening visits begins and they will be scheduled for an in-person enrollment visit within 7 days. Changes in health history will be assessed. The REDCap system will generate the randomization sequence with varied blocks (four and six): 1. ENG implant and 2. LNG IUD. No treatment concealment will occur for participants or providers due to differences in devices and inability to conceal either those inserting them, but statisticians not will be aware of treatment assignment, only study arm 1 or 2. Devices will be inserted via standard practice. Participant-preference arm- those who opt out of randomization will select their method at the same cycle timing as those randomized. An additional survey will query reasoning for declining randomization and decision-making regarding device selection. All other study procedures will remain the same as those randomized. In-person follow-up visit: The participant will have a follow-up visit ~2mo after contraceptive method placement. Changes in health history will be assessed and for those with an IUD, a string check performed. In-person Exit visit: The participant will have an exit visit ~6mo after contraceptive method placement. Changes in health history will be assessed and for those with an IUD, a string check performed. Those who desire contraceptive method continuation may keep their devices and continue use based on method approval. Analyses. The goal of Aim 1 is to calculate a point estimate of the proportion of participants willing to be randomized to either an ENG implant or LNG IUD. A 95% confidence interval around this estimate will describe its variability. Secondary outcomes include the proportion of participants that agree to participation in the patient preference arm, and of these, reasoning for method selection and unacceptability of randomization. The investigators will use descriptive statistics, as well as thematic findings from free text response options. Aim 2 will assess changes in IBD symptom scores and QOL measures after contraceptive initiation. Cycle timing will be calculate based on reported cycle length and on bleeding intervals in the 2 months prior to LARC insertion and other metrics analyzed for changes by ovulation timing and menses. The investigators will calculate proportion of participants who change IBD treatment during the study timeframe, as this may inform sampling in future trial. The investigators will also calculate the proportion enrolled who had reported cyclical symptoms in 4 or more of their pre-enrollment cycles but then do not have cyclical changes in their 2 spontaneous cycles in the study, as this impacts future sample size calculations. The Harvey Bradshaw Index, partial Mayo Score, IBD-Q Short Form, and the Contraceptive Sexual Acceptability Scale will all be scored as appropriate. 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. The investigators will compare means in symptom scores and QOL before and after contraceptive initiation using paired t-tests, and will compare variations in these means across menstrual cycle phases using linear regression, controlling for contraceptive initiation as a dichotomous variable. An Autoregressive Integrated Moving Average (ARIMA) l will be examined if data collection exceeds 100 observations. This approach will be utilized in future studies to better understand changes in patient reported outcomes overtime. Aim 3 will assess the proportion of participants with hsCRP and fecal calprotectin levels within a 'normal' range before and after contraceptive initiation through chi-square tests. Additionally, The investigators will compare mean hsCRP and fecal calprotectin levels before and after contraceptive initiation using paired t-tests. The investigators will compare variations means across menstrual cycle phases using linear regression, controlling for contraceptive initiation as a dichotomous variable. The investigators will look for difference in inflammatory marker levels across levels of IBD symptom scores to determine whether to include these symptom scores as covariates in our regression models. No comparisons will be made between participants, as baseline levels may vary and never be in a "normal" range for some markers.

Facilities

Sequence: 198562972
Name University of Utah
City Salt Lake City
State Utah
Zip 84132
Country United States

Facility Contacts

Sequence: 27934829 Sequence: 27934830
Facility Id 198562972 Facility Id 198562972
Contact Type primary Contact Type backup
Name Sarah Elliott Name Erin Johnson
Email sarah.elliott@hsc.utah.edu Email erin.p.johnson@hsc.utah.edu

Browse Interventions

Sequence: 95269432 Sequence: 95269433 Sequence: 95269434 Sequence: 95269435 Sequence: 95269436 Sequence: 95269437
Mesh Term Etonogestrel Mesh Term Contraceptive Agents, Hormonal Mesh Term Contraceptive Agents Mesh Term Reproductive Control Agents Mesh Term Physiological Effects of Drugs Mesh Term Contraceptive Agents, Female
Downcase Mesh Term etonogestrel Downcase Mesh Term contraceptive agents, hormonal Downcase Mesh Term contraceptive agents Downcase Mesh Term reproductive control agents Downcase Mesh Term physiological effects of drugs Downcase Mesh Term contraceptive agents, female
Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Conditions

Sequence: 51771406 Sequence: 51771407 Sequence: 51771408
Name Inflammatory Bowel Diseases Name Contraception Name Menstrual Problem
Downcase Name inflammatory bowel diseases Downcase Name contraception Downcase Name menstrual problem

Id Information

Sequence: 39840890
Id Source org_study_id
Id Value IRB_00160085

Countries

Sequence: 42238174
Name United States
Removed False

Design Groups

Sequence: 55189401 Sequence: 55189402
Group Type Active Comparator Group Type Active Comparator
Title Etonogestrel contraceptive implant Title 52mg levonorgestrel intrauterine device
Description Participants who randomize to the implant or choose it in the participant preference arm will have it inserted during their 2nd menses after their screening visit. Description Participants who randomize to the hormonal IUD or choose it in the participant preference arm will have it inserted during their 2nd menses after their screening visit.

Interventions

Sequence: 52092972 Sequence: 52092973
Intervention Type Device Intervention Type Device
Name ENG Implant Name LNG IUD
Description This is an FDA approved contraceptive device Description This is an FDA approved contraceptive device

Keywords

Sequence: 79214469 Sequence: 79214470
Name intrauterine device Name subdermal contraceptive implant
Downcase Name intrauterine device Downcase Name subdermal contraceptive implant

Design Outcomes

Sequence: 176083275 Sequence: 176083276 Sequence: 176083277 Sequence: 176083278 Sequence: 176083279 Sequence: 176083280 Sequence: 176083281 Sequence: 176083282
Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary
Measure Acceptability of randomization Measure Change in IBD symptom scores in participants with Crohn's disease by menstrual timing and contraceptive Measure Change in IBD symptom scores in participants with ulcerative colitis by menstrual timing and contraceptive Measure Change in IBD quality of life score by menstrual timing and contraceptive Measure Effect of contraceptive initiation on C Reactive Protein level Measure Effect of contraceptive initiation and menstrual phase on C Reactive Protein level Measure Effect of contraceptive initiation on fecal calprotectin level Measure Effect of contraceptive initiation and menstrual phase on fecal calprotectin level
Time Frame 2 months after screening visit Time Frame Measured daily on follow-up surveys for up to 8 months Time Frame Measured daily on follow-up surveys for up to 8 months Time Frame Measured daily on follow-up surveys for up to 8 months Time Frame Measured at baseline and exit visit Time Frame Measured at baseline and weekly for 2 months until contraceptive initiation, then monthly for 6 months Time Frame Measured at baseline and monthly for 8 months with contraceptive initiation at the 2 month timepoint Time Frame Measured at baseline and monthly for 8 months with contraceptive initiation at the 2 month timepoint
Description Proportion of participants willing to be randomized to an LNG IUD or ENG implant Description Variation in mean Harvey Bradshaw Index by menstrual phase prior to contraceptive initiation and changes from pre to post-method initiation. Scores of 5-7, 8-15 and >16 indicate mild, moderate and severe disease. A score of ≤4 denotes clinical remission and a drop ≥3 clinical response. Description Variation in mean Partial Mayo Score (pMS) both by menstrual phase prior to contraceptive initiation and changes from pre to post-method initiation. The pMS pMS (without endoscopic subscore) varies from 0 to 9. Lower scores are correlated with clinical response or remission. Description Variation in mean mean Inflammatory Bowel Disease Short Form Score (SIBDQ) both by menstrual phase prior to contraceptive initiation and changes from pre to post-method initiation. The SIBDQ is a shortened (10-item) version of a QOL survey with range 10-70. A 9-point change is generally considered a response amd higher scores indicate improved QOL. Description Proportion of participants with 'Normal' range (based on reference lab values or participant known baseline) at 1st study visit and compared to exit visit Description Trend in mean of participant values over study timeframe of 8 months Description Proportion of participants with 'Normal' range (based on reference lab values or participant known baseline) at 1st study visit and compared to exit visit Description Trend in mean of participant values over study timeframe of 8 months

Browse Conditions

Sequence: 191876817 Sequence: 191876818 Sequence: 191876819 Sequence: 191876820 Sequence: 191876821 Sequence: 191876822 Sequence: 191876823
Mesh Term Intestinal Diseases Mesh Term Inflammatory Bowel Diseases Mesh Term Menstruation Disturbances Mesh Term Gastrointestinal Diseases Mesh Term Digestive System Diseases Mesh Term Gastroenteritis Mesh Term Pathologic Processes
Downcase Mesh Term intestinal diseases Downcase Mesh Term inflammatory bowel diseases Downcase Mesh Term menstruation disturbances Downcase Mesh Term gastrointestinal diseases Downcase Mesh Term digestive system diseases Downcase Mesh Term gastroenteritis Downcase Mesh Term pathologic processes
Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Sponsors

Sequence: 47946510
Agency Class OTHER
Lead Or Collaborator lead
Name University of Utah

Overall Officials

Sequence: 29050041
Role Principal Investigator
Name Lori Gawron
Affiliation University of Utah

Central Contacts

Sequence: 11928003 Sequence: 11928004
Contact Type primary Contact Type backup
Name Amy Orr Name Corinne Sexsmith
Phone 801-213-2774 Phone 801-213-2522
Email amy.orr@hsc.utah.edu Email corinne.sexsmith@hsc.utah.edu
Role Contact Role Contact

Design Group Interventions

Sequence: 67662200 Sequence: 67662201
Design Group Id 55189401 Design Group Id 55189402
Intervention Id 52092972 Intervention Id 52092973

Eligibilities

Sequence: 30530981
Gender Female
Minimum Age 18 Years
Maximum Age 45 Years
Healthy Volunteers No
Criteria Inclusion Criteria: Between 18-45 years old Fluent in English and/or Spanish Have biopsy-proven IBD Have a regular menstrual cycle (21-35 days) Report recurrent cyclical IBD symptoms in >50% of menstrual cycles in past 6 months (e.g. change in bowel habits, abdominal pain, etc.) Intend to use a LNG IUD or ENG implant and willing to consider randomization Not at risk for pregnancy (e.g. sterilization, same-sex partner, abstinence) or willing to use condoms until 7 days after LARC device initiation Exclusion Criteria: Current pregnancy (+urine pregnancy test in clinic) Breastfeeding without resumption of 2 normal menses Contraindication to ENG implant or LNG IUD (U.S. Medical Eligibility Criteria for Contraceptive Use13 category 3 or 4) History of intolerance/ side effects with ENG Implant/LNG IUD Vaginal bleeding of unknown etiology Use of contraceptive steroids in past 30d without resumptions of menses Active, steroid-requiring IBD flare in past 30 days
Gender Description Must have menstrual cycles
Gender Based True
Adult True
Child False
Older Adult False

Calculated Values

Sequence: 254108436
Number Of Facilities 1
Registered In Calendar Year 2022
Were Results Reported False
Has Us Facility True
Has Single Facility True
Minimum Age Num 18
Maximum Age Num 45
Minimum Age Unit Years
Maximum Age Unit Years
Number Of Primary Outcomes To Measure 8

Designs

Sequence: 30279545
Allocation Randomized
Intervention Model Sequential Assignment
Observational Model
Primary Purpose Other
Time Perspective
Masking Single
Masking Description No treatment concealment will occur for participants or providers due to differences in devices and inability to conceal either those inserting them, but statisticians not will be aware of treatment assignment, only study arm 1 or 2.
Intervention Model Description The REDCap system will generate the randomization sequence with varied blocks (four and six): 1. ENG implant and 2. LNG IUD.
Outcomes Assessor Masked True

Intervention Other Names

Sequence: 26478952 Sequence: 26478953 Sequence: 26478954
Intervention Id 52092972 Intervention Id 52092973 Intervention Id 52092973
Name Nexplanon Name Mirena Name Liletta

Responsible Parties

Sequence: 28658488
Responsible Party Type Sponsor