Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03646708 |
| Other study ID # |
201805058 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 9, 2018 |
| Est. completion date |
May 30, 2023 |
Study information
| Verified date |
February 2022 |
| Source |
Washington University School of Medicine |
| Contact |
Darren Nix |
| Phone |
314-362-3201 |
| Email |
nixd[@]wustl.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The small bowel (SB) is involved in ~70% of patients with Crohn's disease (CD). There is an
unmet need for accurate and clinically meaningful methods to measure small bowel Crohn's
Disease (SBCD) activity. This is particularly relevant as the field moves towards
"treat-to-target" management strategies. The overall objective of this proposal is to
establish that radiologic transmural response (TR) and a novel proteomic biomarker are
accurate and clinically meaningful predictors of SBCD inflammatory activity and response to
biologic therapy. To address this objective, we will establish a prospectively followed
cohort of SBCD patients starting a new biologic therapy. These patients will be
comprehensively phenotyped using state of the art MRE imaging, proteomic profiling and
clinical disease activity indices. We will use this innovative approach of triangular
phenotyping to address our central hypothesis that "Corticosteroid-free remission at 52 weeks
after biologic therapy initiation is predicted by short term radiologic TR or early changes
in serum proteomic biomarker profiles". Serum proteomic biomarker profiles will be evaluated
using SOMAscanTM (SomaLogic, Inc., Boulder, Colorado, USA), a novel platform allowing
high-throughput analysis of proteins through Slow Off-rate Modified DNA Aptamer
(SOMAmer)-based capture array. Our preliminary data using SOMAscan identified a panel of 12
serum proteins whose differential expression pattern from Week 0 to week 6 after starting a
biologic can predict week 14 clinical remission in SBCD patients. The significance of this
proposal is that the development of an early predictive model using radiological and serum
endpoints will facilitate a personalized algorithmic approach to identify patients with SBCD
who will benefit from treatment escalation or change to a different biologic. Furthermore, it
will be used to generate a tangible career tool of a prospectively enrolled patient cohort to
further study radiologic and biomarker predictors of response in SBCD. This award will also
enhance the career of the principal investigator by facilitating acquisition of an enhanced
skill set in clinical research, bioinformatics and biomarker discovery.
Description:
Patients entering the study will be evaluated by the investigator for all inclusion and
exclusion criteria. Once inclusion and exclusion criteria have been determined, all subjects
will sign an Internal Review Board (IRB)/Independent Ethics Committee (IEC) approved consent
document, which complies with regulatory requirements, prior to any study activities.
Subjects will be given adequate time to read and consider the consent document and all study
information. They will have the opportunity to ask questions of the investigator(s) and the
study team about the study, as well as risks and benefits, prior to signing the document.
Baseline Visit
Baseline assessments will be collected from the clinical care record from the standard of
care visit(s) done most prior to the subject receiving their first dose of biologic All
assessments will be done/collected prior to the subject's first does of biologic. The
baseline visit will consist of the following:
- Demographic information: Date of birth, gender, and race will be collected.
- Clinical assessment: These assessments will be done by the study team prior to the
subject receiving the first dose of vedolizumab.
- Physical Exam Findings: Physical exam findings will be taken from the patient's clinical
care record from the standard of care visit most recently preceding the initial dose of
vedolizumab. If this data is not available from the visit, the information will be
obtained from the subject during a separate visit to the clinic by the study team, and
prior to the first dose of vedolizumab.
- Blood Tests (C-reactive, Albumin, Hematocrit, SOMAscan panel
- Stool Collection: At the time of consent, participants will be provided a stool
collection kit and asked to collect a small amount of stool when they have a bowel
movement, prior to their first dose of biologic, for genetic, microbiome, or biomarker
analysis. If the patient is unable to provide a stool sample, permission may be asked to
obtain a rectal swab, or a sample collection kit will be mailed to them and asked to
mail the stool sample back to us in a prepaid envelope. If the patient is in the
hospital and tests have been ordered on their stool, stool may be collected from what is
left over after the tests have been completed. The stool will be assigned a unique
specimen code. The messenger ribonucleic acid (mRNA) in the stool would be extracted and
the genetic expression profile of this sample would be determined. All participants
consent to having details from their medical records (age, ethnicity, medications,
surgery, tobacco use, family history, disease activity, disease history) at the
Washington University Medical Center (WUSM), and entered into a database associated with
a patient code. If the patient's records do not include all relevant information, a
study team member may obtain this information directly from the patient.
The specimen(s) will not have the participant name or address on it; it will be labeled with
a code in order to protect the patient's health information and identity. The specimen(s)
will be stored in locked freezers in a locked laboratory at WUSM. All coded specimens will be
linked to study participants on a separate master list, which will be stored in a locked
cabinet (the study coordinators have the only key) or a password protected file. This
information will be kept separate from the clinical data.
- Endoscopic Assessment: A baseline ileocolonoscopy may be additionally performed as
standard of care at the discretion of the treating gastroenterologist to confirm active
SBCD, either before or after the MRE. Subjects will undergo standard bowel preparation
at the discretion of the treating gastroenterologist prior to ileocolonoscopy. If
treatment was required after the ileocolonoscopy, treatment will not be initiated until
after the baseline MRE is completed. Subjects who have had endoscopic assessment with
biopsies from the ileum confirming small bowel Crohn's disease as a part of their
standard of care treatment in the six (6) months prior to study enrollment may be used
for the baseline study assessment, at the investigator's discretion. If a more recent
endoscopic assessment is done with this reporting, the more recent assessment will be
used.
- Radiological Assessment: Radiological assessment will be performed on all patients as a
part of their clinical standard of care prior to initiating vedolizumab. Clinical read
will be evaluated using the assessment tool in Appendix B and guidance from Appendix A.
Week 6 Visit (+/- 1 week)
Week 6 Visit assessment will be done 6 weeks (+/- 1 week) after initiating biologic as a part
of clinical standard of care treatment as described in this protocol. The visit will consist
of the following:
- Clinical assessment:
- Blood Tests (C-reactive, Albumin, Hematocrit, SOMAscan panel Week 14 Visit (+/- 2 weeks)
Week 14 Visit assessment will be done 14 weeks (+/- 2 weeks) after initiating biologic as a
part of clinical standard of care treatment as described in this protocol. The visit will
consist of the following:
- Clinical assessment:
- Physical Exam Findings: Physical exam findings will be taken from the patient's clinical
care record from the most recent standard of care visit. If this data is not available
from the visit, the information will be obtained from the subject during a separate
visit to the clinic by the study team.
- Blood Tests (C-reactive, Albumin, Hematocrit, SOMAscan panel
- Stool Collection: As above referenced in the Baseline Visit.
- Radiological Assessment:
Phone Visit The Phone Visit assessment will be done at week 26 and 40.
- Clinical assessment: Week 52 Visit (+/- 4 weeks)
Week 52 assessments will be done 52 weeks (+/- 4 weeks) after initiating biologic as a part
of clinical standard of care treatment as described in this protocol. The visit will consist
of the following:
- Clinical assessment:
- Physical Exam Findings: Physical exam findings will be taken from the patient's clinical
care record from the most recent standard of care visit. If this data is not available
from the visit, the information will be obtained from the subject during a separate
visit to the clinic by the study team.
- Blood Tests:
- Radiological Assessment: Radiological assessment will be performed on all patients as a
part of their clinical standard of care. Clinical read will be evaluated using the
assessment tool in Appendix B and guidance from Appendix A.
- Optional Endoscopic Assessment: Subjects can have additional endoscopic assessment as a
part of their standard of care treatment, and this report may be used for the study
assessment.
- Disease Progression Assessment: In order to assess the Disease Progression endpoint the
following will be assessed for the time point between the Week 16 Visit MRE and the Week
52 Visit MRE:
- Any hospitalization for disease flare or complications of the disease
- Need for surgery related to CD
- Need for rescue corticosteroids The treating gastroenterologists will be blinded to
the results of radiological TR although they will have access to the clinical read
in the electronic medical record.
