Fluorescence Imaging of Adalimumab-680LT in Inflammatory Bowel Disease
- Conditions
- Crohn DiseaseUlcerative Colitis
- Interventions
- Other: Control
- Registration Number
- NCT06117423
- Lead Sponsor
- University Medical Center Groningen
- Brief Summary
Crohn's Disease (CD) and Ulcerative Colitis (UC) are chronic inflammatory bowel diseases (IBD). Adalimumab is a human monoclonal antibody against TNF-alpha, a pro-inflammatory cytokine that mediates the inflammatory response in IBD upon binding to the TNF receptors. Primary non-response to adalimumab is high in both CD and UC. Currently, there are no predictors of response to adalimumab and the actual mechanism of action has not yet been elucidated. To gain better understanding of the drug targeting of adalimumab in IBD, the University Medical Center Groningen (UMCG) developed fluorescently labeled adalimumab (adalimumab-680LT). This study aims to assess the safety and the optimal dose of adalimumab-680LT to visualize and potentially quantify the local drug concentration and predict treatment response in IBD patients using in vivo and ex vivo fluorescence molecular imaging (FMI).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 21
- Established IBD diagnosis (UC or CD)
- Active disease (clinically defined as at least mild activity using dedicated scoring indices and biochemically defined by a fecal calprotectin > 60 µg/g, measured within the last 6 weeks before inclusion)
- Patients must be eligible for adalimumab therapy
- Clinical indication for an endoscopic procedure
- Age: 18 years or older
- Written informed consent
- For female patients of premenopausal age with intact reproductive organs or who are less than 2 years postmenopausal, a negative pregnancy test must be available.
- Pregnancy or breast feeding
- Female patient of premenopausal age who does not use any reliable form of contraception at the time of adalimumab-680LT administration and the following 10 weeks.
- Medical or psychiatric conditions that compromise the patient's ability to give informed consent
- Prior anti-TNF therapy in the last 6 weeks before inclusion
- Active extra gastrointestinal manifestations of Crohn's disease
- Previous treatment with adalimumab and detectable anti-adalimumab antibodies levels
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description No administration of adalimumab-680LT Control Patients did not receive adalimumab-680LT, but underwent a Fluorescence Molecular Imaging procedure to serve as a control group and compare results with patients receiving the tracer 25 mg adalimumab-680LT Adalimumab-680LT Patients received 25 mg adalimumab-680LT and underwent a Fluorescence Molecular Imaging procedure 4.5 mg adalimumab-680LT Adalimumab-680LT Patients received 4.5 mg adalimumab-680LT and underwent a Fluorescence Molecular Imaging procedure 15 mg adalimumab-680LT Adalimumab-680LT Patients received 15 mg adalimumab-680LT and underwent a Fluorescence Molecular Imaging procedure >14 weeks of adalimumab therapy + optimal dose adalimumab-680LT Adalimumab-680LT Patients who received the optimal dose during the first Fluorescence Molecular Imaging procedure are invited for a second procedure after at least 14 weeks of adalimumab therapy. They will receive the optimal dose adalimumab-680LT and will undergo another Fluorescence Molecular Imaging procedure
- Primary Outcome Measures
Name Time Method Investigate the feasibility of using FME to detect adalimumab-680LT signals 12 months Evaluating the performance of FME for detecting adalimumab-680LT signals. This evaluation will be based on a visual evaluation during FME (visible signal yes/no), TBR and CNR calculations and MDSFR/SFF measurements.
Temperature Five minutes before, and five and sixty minutes after tracer administration Degrees Celsius
Blood pressure Five minutes before, and five and sixty minutes after tracer administration Millimeters of mercure (mmHg)
Determining the optimal imaging dose of adalimumab-680LT 12 months The optimal dose will be based on the adalimumab-680LT signals during FME and ex vivo FMI
Determine the safety of adalimumab-680LT in IBD Until 24 hours after administration Evaluating possible (severe) adverse events (SAE \& AEs)
Heart rate Five minutes before, and five and sixty minutes after tracer administration Beats per minute
Investigate the feasibility of using ex vivo FMI to detect adalimumab-680LT 12 months Evaluating the performance of ex vivo FMI for detecting adalimumab-680LT signals. This evaluation will be based on mean fluorescence intensities (MFIs) of biopsies and fluorescence/light sheet microscopy.
- Secondary Outcome Measures
Name Time Method Quantify the fluorescence signals of the tracer in vivo by using single-fiber reflectance/single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlate these measurements to tracer dose, in vivo fluorescence intensities and inflammation severity 12 months Quantification of MDSFR/SFF measurements in inflamed tissue compared to measurements in non-inflamed tissue. Positive correlation between MDSFR/SFF measurements and dose/inflammation severity?
Investigate a potential correlation of ex vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of adalimumab therapy regimen in patients with IBD 12 months Evaluation of the potential correlation ex vivo will be based on MFIs of biopsies, fluorescence microscopy results, and tracer concentrations inside biopsies before and after at least 14 weeks of adalimumab treatment
To correlate ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination inside the obtained biopsies 12 months Histologically ascertained tissue types (qualitative):
Normal (non-inflamed) ileal, colon and rectal tissue Inflamed ileum, colon and rectum tissue Random ''high-fluorescent'' tissue Random ''Non-fluorescent'' tissueInvestigate a potential correlation of in vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of adalimumab therapy regimen in patients with IBD 12 months Evaluation of the potential correlation in vivo will be based on in vivo fluorescence images and the MDSFR/SFF measurements before and after at least 14 weeks of adalimumab treatment
To assess tracer stability, tracer distribution and tracer concentration, and to identify the composition of immune cells ex vivo to learn more about adalimumab mucosal target cells 12 months Fluorescence (confocal) microscopy with additional use of immune panels and spatial transcriptomics analysis (before and after at least 14 weeks of adalimumab treatment). Measurements of the adalimumab-680LT concentration by light-sheet microscopy after tissue clearing, insights in adalimumab-target cells and presence of immune cells inside the biopsies and blood samples by flow cytometry and assessment of tracer stability by Western Blot
Trial Locations
- Locations (1)
University Medical Center Groningen
🇳🇱Groningen, Netherlands