Ignite Creation Date:
2024-10-25 @ 7:48 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06647823
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-16
Brief Title:
Calculating the LEmann IndeX Using InTEstiNal Ultrasound
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Calculating the LEmann IndeX Using InTEstiNal Ultrasound
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EXTENT
Brief Summary:
The goal of this clinical trial is to assess and quantitatively measure structural bowel damage in Crohns disease CD with the Lèmann-Index LI for Intestinal Ultrasound IUS IUS is a non-invasive easily repeated and well tolerated tool with no bowel preparations With this study the investigators aim to show that IUS can replace Magnetic Resonance Enterography MRE which has been used to develop the original Lèmann-Index to evaluate structural bowel damage
For each patient IUS and MRE and Colonoscopy if the colon is involved will be performed within a two-month timeframe
For each patient IUS and MRE and Colonoscopy if the colon is involved will be performed within a two-month timeframe
Detailed Description:
EXTENT will be a multicenter cross-sectional study including 102 Crohns disease CD patients stratified by known or suspected CD location small bowel and colon and by disease duration 2 years 2 years and 10 years and 10 years The investigators will recruit patients with an established diagnosis of CD with no restriction per disease activity surgical history or CD medication
Enrolled participants will undergo baseline blood work stool studies and both MRE and IUS
Individuals with colonic involvement will also undergo colonoscopy Patients will also answer to the IBD disability index questionnaire to assess the patients functional status All examinations performed will be standard of care needed for patient monitoring and the results will be used for the purpose of this study Clinical data imaging and colonoscopy assessments will be collected from participants prospectively over a period of 8 weeks IUS and MRE data will be centrally read by three central readers blinded to the local reader grading of lesions
The primary objective is to demonstrate that IUS can replace MRE to evaluate small bowel global damage and colon global damage excluding rectum in Crohns disease patients with small bowel andor colonic involvement
Additive objectives concerning IUS versus MRE are
To demonstrate that IUS can replace MRE colonoscopy to evaluate colon global damage excluding rectum
To demonstrate that IUS can replace MRE in assessing segmental damage in patients with CD terminal ileum
To demonstrate that IUS can replace MRE colonoscopy in assessing segmental damage in patients with CD all colonic segments except rectum
To test if local investigators can replace central readers to evaluate small bowel colon and global LI-IUS and LI-MRE
To quantify how much higher is IUS acceptability relatively to MRE and colonoscopy acceptabilities
Inter-reader variation study aims
To demonstrate that it is possible for central readers to evaluate in a reliable way small bowel colon and global LI-IUS scores
To confirm that it is possible for central readers to evaluate in a reliable way small bowel colon and global LI-MRE scores
To compare the intra- and inter-reader reliability levels of small bowel colon and global LI-IUS scores and of small bowel colon and global LIMRE scores
To demonstrate that it is possible for central readers to re-evaluate in a reliable way small bowel colon and global LI-IUS scores
To confirm that it is possible for central readers to re-evaluate in a reliable way small bowel colon and global LI-MRE scores
Other objectives are
Relationship between IBD disability and global small bowel and colon damage as evaluated by IUS and by MRE
Comparison of the presence and distribution of stricturing and penetrating lesions using IUS and MRE across severity levels
The exploratory objectives are
To evaluate potential intestinal ultrasound parameters equivalent to wall hyperenhancement in MRE - used to define type 1 stricturing lesions
To evaluate potential intestinal ultrasound parameters equivalent to mural stratification in MRE - used to define type 2 stricturing lesions
To identify additional features of bowel wall damage on intestinal ultrasound
Inclusion criteria
Adult patients 18 years old
Established diagnosis of CD in line with international diagnostic criteria
Examinations needed as standard of care
Patients able to understand the information provided to them and to give written informed consent for the study
Exclusion criteria
Pregnant women or patients willing the conceive
Patients unwilling or unable to provide informed written consent
Uncertain CD diagnosis or Colitis indeterminata
Patients with disease limited to the upper gastrointestinal tract rectum or perianal CD
Patients with a contraindication for MR colonoscopy andor ultrasound
Patients with allergy to gadolinium chelated or with Estimated Glomerular Filtration Rate 60 mLmin173m2
Intestinal Ultrasound
IUS examinations will be performed by a gastroenterologist or radiologist using different US devices and low-frequency and mid to high-frequency probes from various manufacturers IUS examinations will be done preferably in a non-fasting state and will consistently capture all small bowel jejunum and ileum and colonic segments cecum ascending colon transverse colon descending colon and sigmoid colon All investigators in the study will be trained in LI calculation and on the specific lesions that should be assessed to calculate the LI Appendix 4 Both probes low-frequency and mid to highfrequency should be used to assess IUS lesions for IUS-Lémann index The affected small bowel or colonic segments will be graded for the worse type of stricturing or penetrating lesion The researcher will record all intestinal segments and upload the cineloops to a central reading platform and indicate in real time the lesions observed in each affected segment This will allow the investigators to test feasibility of use of LI-IUS in daily clinical practice
If small bowel is involved the extent of disease will be measured and the number of 20 cm segments affected will be collected If more than one pathological 20-cm small bowel segment is found they will be labeled as SB1 beginning in the ileocecal valve or ileocolic anastomosis SB2 SB3 etc preferably adding a body marker OR text for location ex LLQ RUQ A complete small bowel scan cineloop will be recorded to assess small bowel lesions and disease extension All pathological small bowel segments identified during the examination need to be recorded in a longitudinal section to allow for disease extension measurement with a cineloop of 5-10 seconds preferably with a mid to high-frequency probe if the complete segment can be visualized Every pathological small bowel segment should also be recorded in cross-sectional with a cineloop of 5-10 seconds Every colonic segment should be recorded in both cross-sectional and longitudinal planes with a cineloop of 5-10 seconds For the purpose of the LI the cecum is separated from the ascending colon
The cecum corresponds to the colonic segment distal to the ileocecal valve For anatomical reference the cineloop should include if possible the terminal ileum the ileocecal valve and the ileocecal appendix if accessible In non-operated individuals a cineloop starting in the terminal ileum at the right lower quadrant including anatomical landmarks such as psoas muscle andor iliac vessels and following parallel lines along the abdomen extending from the liverstomachribs to the bladderiliac vessels will be recorded For post-operative patients small bowel resection or ileocolonic resection a cineloop starting at the anastomosis and progressing proximally will be recorded To ensure complete small bowel scan the investigators recommend following parallel lines along the abdomen extending from the liverstomachribs to the bladderiliac vessels
Magnetic Resonance Enterography
All MREs will occur at approved centers to ensure quality using oral negative contrast and requiring previous fasting The Baseline MRE with T1 and T2-weighted sequences will use intravenous contrast gadolinium MRE will be centrally read by established blinded experts using the validated Lémann index score grading bowel damage for each segment
Colonoscopy
All participants with colonic involvement will undergo ileocolonoscopy IC after appropriate bowel preparation IC will be locally read using the validated definitions for the calculation of the Lémann index Appendix 6 for each visualized segment Where any segment of the IC is not directly visualized reasons for limitations eg impassable stricture patient factors such as pain etc will be recorded
Cineloops of the entire withdrawal procedure should be stored locally so central reading is still possible in case of any doubt
Statistical Analysis
Intraclass correlation point estimate and 95 confidence interval will be estimated using a two-way random model6 for global small bowel colon LI-IUS and LI-MRE for global colon LI-MRE colonoscopy for IUS and MRE segmental damage terminal ileum and colonic segment except rectum These correlation coefficient estimates will be compared between IUS and MRE through maximum likelihood ratio-test 11
IUS central review will be conducted by IBUS an organization with vast experience and an established platform for ultrasound central review There will be 3 MRE and 3 IUS central reviewers for this project
All 102 cases will be evaluated by 3 central reviewers for inter-rater variability All 102 cases will be evaluated twice by one of the central reviewers to determine intra-rater variability
Intraclass correlation will be applied to estimate intra- and inter-reader reproducibility levels of global small bowel colon LI-IUS and LI-MRE performances When comparing global small bowel colon LIIUS evaluations between local reader and central readers the central readers data will be summarized by using either the common evaluation when at least 2 out of the 3 central readers agree or the intermediate evaluation when the 3 readers disagree omitting the most and the less severe evaluations
For the other endpoints standard nonparametric statistical methods will be used
Enrolled participants will undergo baseline blood work stool studies and both MRE and IUS
Individuals with colonic involvement will also undergo colonoscopy Patients will also answer to the IBD disability index questionnaire to assess the patients functional status All examinations performed will be standard of care needed for patient monitoring and the results will be used for the purpose of this study Clinical data imaging and colonoscopy assessments will be collected from participants prospectively over a period of 8 weeks IUS and MRE data will be centrally read by three central readers blinded to the local reader grading of lesions
The primary objective is to demonstrate that IUS can replace MRE to evaluate small bowel global damage and colon global damage excluding rectum in Crohns disease patients with small bowel andor colonic involvement
Additive objectives concerning IUS versus MRE are
To demonstrate that IUS can replace MRE colonoscopy to evaluate colon global damage excluding rectum
To demonstrate that IUS can replace MRE in assessing segmental damage in patients with CD terminal ileum
To demonstrate that IUS can replace MRE colonoscopy in assessing segmental damage in patients with CD all colonic segments except rectum
To test if local investigators can replace central readers to evaluate small bowel colon and global LI-IUS and LI-MRE
To quantify how much higher is IUS acceptability relatively to MRE and colonoscopy acceptabilities
Inter-reader variation study aims
To demonstrate that it is possible for central readers to evaluate in a reliable way small bowel colon and global LI-IUS scores
To confirm that it is possible for central readers to evaluate in a reliable way small bowel colon and global LI-MRE scores
To compare the intra- and inter-reader reliability levels of small bowel colon and global LI-IUS scores and of small bowel colon and global LIMRE scores
To demonstrate that it is possible for central readers to re-evaluate in a reliable way small bowel colon and global LI-IUS scores
To confirm that it is possible for central readers to re-evaluate in a reliable way small bowel colon and global LI-MRE scores
Other objectives are
Relationship between IBD disability and global small bowel and colon damage as evaluated by IUS and by MRE
Comparison of the presence and distribution of stricturing and penetrating lesions using IUS and MRE across severity levels
The exploratory objectives are
To evaluate potential intestinal ultrasound parameters equivalent to wall hyperenhancement in MRE - used to define type 1 stricturing lesions
To evaluate potential intestinal ultrasound parameters equivalent to mural stratification in MRE - used to define type 2 stricturing lesions
To identify additional features of bowel wall damage on intestinal ultrasound
Inclusion criteria
Adult patients 18 years old
Established diagnosis of CD in line with international diagnostic criteria
Examinations needed as standard of care
Patients able to understand the information provided to them and to give written informed consent for the study
Exclusion criteria
Pregnant women or patients willing the conceive
Patients unwilling or unable to provide informed written consent
Uncertain CD diagnosis or Colitis indeterminata
Patients with disease limited to the upper gastrointestinal tract rectum or perianal CD
Patients with a contraindication for MR colonoscopy andor ultrasound
Patients with allergy to gadolinium chelated or with Estimated Glomerular Filtration Rate 60 mLmin173m2
Intestinal Ultrasound
IUS examinations will be performed by a gastroenterologist or radiologist using different US devices and low-frequency and mid to high-frequency probes from various manufacturers IUS examinations will be done preferably in a non-fasting state and will consistently capture all small bowel jejunum and ileum and colonic segments cecum ascending colon transverse colon descending colon and sigmoid colon All investigators in the study will be trained in LI calculation and on the specific lesions that should be assessed to calculate the LI Appendix 4 Both probes low-frequency and mid to highfrequency should be used to assess IUS lesions for IUS-Lémann index The affected small bowel or colonic segments will be graded for the worse type of stricturing or penetrating lesion The researcher will record all intestinal segments and upload the cineloops to a central reading platform and indicate in real time the lesions observed in each affected segment This will allow the investigators to test feasibility of use of LI-IUS in daily clinical practice
If small bowel is involved the extent of disease will be measured and the number of 20 cm segments affected will be collected If more than one pathological 20-cm small bowel segment is found they will be labeled as SB1 beginning in the ileocecal valve or ileocolic anastomosis SB2 SB3 etc preferably adding a body marker OR text for location ex LLQ RUQ A complete small bowel scan cineloop will be recorded to assess small bowel lesions and disease extension All pathological small bowel segments identified during the examination need to be recorded in a longitudinal section to allow for disease extension measurement with a cineloop of 5-10 seconds preferably with a mid to high-frequency probe if the complete segment can be visualized Every pathological small bowel segment should also be recorded in cross-sectional with a cineloop of 5-10 seconds Every colonic segment should be recorded in both cross-sectional and longitudinal planes with a cineloop of 5-10 seconds For the purpose of the LI the cecum is separated from the ascending colon
The cecum corresponds to the colonic segment distal to the ileocecal valve For anatomical reference the cineloop should include if possible the terminal ileum the ileocecal valve and the ileocecal appendix if accessible In non-operated individuals a cineloop starting in the terminal ileum at the right lower quadrant including anatomical landmarks such as psoas muscle andor iliac vessels and following parallel lines along the abdomen extending from the liverstomachribs to the bladderiliac vessels will be recorded For post-operative patients small bowel resection or ileocolonic resection a cineloop starting at the anastomosis and progressing proximally will be recorded To ensure complete small bowel scan the investigators recommend following parallel lines along the abdomen extending from the liverstomachribs to the bladderiliac vessels
Magnetic Resonance Enterography
All MREs will occur at approved centers to ensure quality using oral negative contrast and requiring previous fasting The Baseline MRE with T1 and T2-weighted sequences will use intravenous contrast gadolinium MRE will be centrally read by established blinded experts using the validated Lémann index score grading bowel damage for each segment
Colonoscopy
All participants with colonic involvement will undergo ileocolonoscopy IC after appropriate bowel preparation IC will be locally read using the validated definitions for the calculation of the Lémann index Appendix 6 for each visualized segment Where any segment of the IC is not directly visualized reasons for limitations eg impassable stricture patient factors such as pain etc will be recorded
Cineloops of the entire withdrawal procedure should be stored locally so central reading is still possible in case of any doubt
Statistical Analysis
Intraclass correlation point estimate and 95 confidence interval will be estimated using a two-way random model6 for global small bowel colon LI-IUS and LI-MRE for global colon LI-MRE colonoscopy for IUS and MRE segmental damage terminal ileum and colonic segment except rectum These correlation coefficient estimates will be compared between IUS and MRE through maximum likelihood ratio-test 11
IUS central review will be conducted by IBUS an organization with vast experience and an established platform for ultrasound central review There will be 3 MRE and 3 IUS central reviewers for this project
All 102 cases will be evaluated by 3 central reviewers for inter-rater variability All 102 cases will be evaluated twice by one of the central reviewers to determine intra-rater variability
Intraclass correlation will be applied to estimate intra- and inter-reader reproducibility levels of global small bowel colon LI-IUS and LI-MRE performances When comparing global small bowel colon LIIUS evaluations between local reader and central readers the central readers data will be summarized by using either the common evaluation when at least 2 out of the 3 central readers agree or the intermediate evaluation when the 3 readers disagree omitting the most and the less severe evaluations
For the other endpoints standard nonparametric statistical methods will be used
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None