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NIR FME of Labelled Vedolizumab to Elucidate the Mechanism of Action and Predicting Response in IBD Patients. (VISION)

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ClinicalTrials.gov Identifier: NCT04112212
Recruitment Status : Not yet recruiting
First Posted : October 2, 2019
Last Update Posted : October 2, 2019
Sponsor:
Information provided by (Responsible Party):
dr. W.B. Nagengast, MD, University Medical Center Groningen

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
Crohn Disease Colitis, Ulcerative Drug: Vedolizumab-800CW Device: Fluorescence endoscopy and spectroscopy Phase 1

Detailed Description:
See brief summary

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Near-infrared Fluorescence Molecular Endoscopy Imaging of Labelled Vedolizumab-800CW to Elucidate the Mechanism of Action and Predicting Response in IBD Patients. A Prospective Pilot Intervention Study:
Estimated Study Start Date : October 1, 2019
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : September 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endoscopy
Drug Information available for: Vedolizumab

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.




Primary Outcome Measures :
  1. Fluorescent signal in patients with IBD [ Time Frame: 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 :
  1. Safety of Vedolizumab-800CW in patients with IBD [ Time Frame: 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.


  2. Quantifying fluorescent signals in patients with IBD [ Time Frame: 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.

  3. FME Ex Vivo analysis to detect target cells [ Time Frame: 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).

  4. Distribution of Vedolizumab in the inflamed gut [ Time Frame: After 18 months when study is completed. ]
    To assess the (sub-)cellular location of vedolizumab-800CW microscopically.

  5. Elucidate vedolizumab target cells [ Time Frame: After 18 months when study is completed. ]
    Identify specific vedolizumab target cells using CITE-seq for single-cell RNA sequencing.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Established diagnosis of IBD, or Ulcerative Colitis (UC) or Crohn's Disease (CD).
  • Vedolizumab naïve and eligible for vedolizumab treatment.
  • Age: 18 years or older.
  • Written informed consent.

Exclusion Criteria:

  • Prior vedolizumab treatment
  • Vedolizumab contraindicated as therapy
  • Pregnancy or breast feeding.
  • Patients younger than 18 years old

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04112212


Contacts
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Contact: W.B. Nagengast, MD, PhD, PharmD +31503612620 w.b.nagengast@umcg.nl
Contact: R.Y. Gabriels, MSc, MD +31615691998 r.y.gabriels@umcg.nl

Sponsors and Collaborators
University Medical Center Groningen
Investigators
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Principal Investigator: W.B. Nagengast, MD, PhD, PharmD University Medical Center Groningen

Publications:
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Responsible Party: dr. W.B. Nagengast, MD, Principal Investigator, University Medical Center Groningen
ClinicalTrials.gov Identifier: NCT04112212     History of Changes
Other Study ID Numbers: NL69572.042.19
First Posted: October 2, 2019    Key Record Dates
Last Update Posted: October 2, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by dr. W.B. Nagengast, MD, University Medical Center Groningen:
Fluorescence
Endoscopy
Vedolizumab-800CW
Additional relevant MeSH terms:
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Crohn Disease
Colitis, Ulcerative
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Colitis
Colonic Diseases
Vedolizumab
Gastrointestinal Agents