VISION: NIR FME of Labelled Vedolizumab to Elucidate the Mechanism of Action and Predicting Response in IBD Patients.
Study Details
Study Description
Brief Summary
Summary Vision Study
Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic idiopathic inflammatory bowel diseases (IBD). Vedolizumab is a humanized monoclonal antibody against α4β7 integrin, capable of blocking the migration of several immune cells across endothelium expressing MAdCAM-1. Vedolizumab is expensive and primary non-response is high in both CD and UC. Currently there are no predictors of response to vedolizumab and the actual mechanism of action has not yet been elucidated. To clarify the mechanism of action and gain better understanding of the high primary non-response rates, the University Medical Center Groningen (UMCG) developed a tracer fluorescently labeling vedolizumab. This study aims to gain insight into vedolizumab distribution and concentrations in the gut. The current study aims to identify the vedolizumab target cells in the inflamed gut mucosa using near-infrared fluorescence molecular endoscopy (NIR-FME), spectroscopy and confocal laser endomicroscopy (CLE). By gaining insight into local vedolizumab concentrations, drug distribution and by discovering target cells, we expect to gain insight into the mechanism of action, gather data with which to optimize vedolizumab dosing, and to learn to predict therapy response in the individual patient.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
See brief summary
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IV administration of vedolizumab-800CW The tracer will be intraveniously administrered 2 or 3 days before the colonoscopy procedure (with the near infrared fluorescence endoscopy platform). |
Drug: Vedolizumab-800CW
Intraveniously administration of vedolizumab-800CW.
Device: Fluorescence endoscopy and spectroscopy
Molecular Fluorescence Endoscopy platform A flexible fluorescence fiber-bundle is attached to a fluorescence camera platform to enable the detection of fluorescence signals. The fluorescence fiber-probe is inserted through the standard working channel of the standard clinical endoscope.
|
Outcome Measures
Primary Outcome Measures
- Fluorescent signal in patients with IBD [After 18 months when study is completed.]
Quantification of fluorescent signal after a microdose of vedolizumab-800CW in inflamed and non-inflamed tissue in patients with IBD.
Secondary Outcome Measures
- Safety of Vedolizumab-800CW in patients with IBD [Interim analysis after 30 weeks (at least 5 patients included). Complete data after 18 months when study is completed.]
Collect safety data of vedolizumab-800CW. Checking vital parameters and adverse events caused by the drug or intervention. Register and analyze all AE's, SAE's and SUSAR's caused by vedolizumab-800CW.
- Quantifying fluorescent signals in patients with IBD [Interim analysis after 30 weeks (at least 5 patients included). Complete data after 18 months when study is completed.]
- Quantify the in vivo NIR fluorescent signal of vedolizumab-800CW by means of the MDSFR/SFF spectroscopy probe.
- FME Ex Vivo analysis to detect target cells [After 18 months when study is completed.]
To evaluate the degree of in vivo fluorescence intensity for differences in severity of inflammation and quantify the in vivo NIR fluorescent signal of vedolizumab-800CW using the spectroscopy probe and compare this to the ex vivo fluorescent signal levels in the biopsies taken (immunohistochemistry, RNA and DNA analysis).
- Distribution of Vedolizumab in the inflamed gut [After 18 months when study is completed.]
To assess the (sub-)cellular location of vedolizumab-800CW microscopically.
- Elucidate vedolizumab target cells [After 18 months when study is completed.]
Identify specific vedolizumab target cells using CITE-seq for single-cell RNA sequencing.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Established diagnosis of IBD, or Ulcerative Colitis (UC) or Crohn's Disease (CD).
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Vedolizumab naïve and eligible for vedolizumab treatment.
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Age: 18 years or older.
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Written informed consent.
Exclusion Criteria:
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Prior vedolizumab treatment
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Vedolizumab contraindicated as therapy
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Pregnancy or breast feeding.
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Patients younger than 18 years old
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Medical Center Groningen | Groningen | Netherlands | 9713 GZ |
Sponsors and Collaborators
- University Medical Center Groningen
Investigators
- Principal Investigator: W.B. Nagengast, MD, PhD, PharmD, University Medical Center Groningen
Study Documents (Full-Text)
None provided.More Information
Publications
- Nagengast WB, Hartmans E, Garcia-Allende PB, Peters FTM, Linssen MD, Koch M, Koller M, Tjalma JJJ, Karrenbeld A, Jorritsma-Smit A, Kleibeuker JH, van Dam GM, Ntziachristos V. Near-infrared fluorescence molecular endoscopy detects dysplastic oesophageal lesions using topical and systemic tracer of vascular endothelial growth factor A. Gut. 2019 Jan;68(1):7-10. doi: 10.1136/gutjnl-2017-314953. Epub 2017 Dec 15.
- Tjalma JJJ, Koller M, Linssen MD, Hartmans E, de Jongh SJ, Jorritsma-Smit A, Karrenbeld A, de Vries EG, Kleibeuker JH, Pennings JP, Havenga K, Hemmer PH, Hospers GA, van Etten B, Ntziachristos V, van Dam GM, Robinson DJ, Nagengast WB. Quantitative fluorescence endoscopy: an innovative endoscopy approach to evaluate neoadjuvant treatment response in locally advanced rectal cancer. Gut. 2020 Mar;69(3):406-410. doi: 10.1136/gutjnl-2019-319755. Epub 2019 Sep 18.
- NL69572.042.19