NCT06188637

Ulcerative Colitis Leukocyte TRAfficking After Treatment With Zeposia: the ULTRAZ Study

A Prospective Cell Migration Study in Ulcerative Colitis Patients Treated With Ozanimod (S1P Receptor Antagonist)

• Status: Withdrawn
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Geert D'Haens · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

The ULTRAZ study is designed to better understand the mode of action of S1P receptor modulators. The alteration of leukocyte trafficking due to S1P receptors such as ozanimod is mainly investigated in rodent studies. Several previous studies show a reduced total leukocyte count in peripheral blood and only two study reported the effect of leukocyte subgroups before and after treatment with ozanimod. The change in leukocyte subgroups in peripheral blood as well as colonic mucosa and lymph nodes have not been investigated to our knowledge. Therefore, the aim of this study is to explore the changes in these three compartments.

Detailed description

Ozanimod is a sphingosine-1-phosphate (S1P) receptor modulator, which binds with high affinity to receptor subtypes 1 (S1P1) and 5 (S1P5). Many cell types express S1P1, including vascular endothelial cells, brain cells, and leukocytes. Normally, S1P levels are high in blood, heterogeneous in peripheral lymphoid organs (e.g. lymph nodes and Peyer's patches) and low in tissue, creating a gradient. This gradient results in direct trafficking of leukocytes out of the lymph node and into the circulation. In inflamed tissue, increased levels of S1P have been observed, leading to more leukocyte trafficking to this area. The modulation of the S1P1 receptor by ozanimod causes internalization and desensitization of S1P1 in leukocytes, reducing their migration in response to an increased S1P gradient. Therefore, leukocytes are retained in peripheral lymphoid organs. Previous studies showed a significant - and reversible - reduction of circulating leukocytes in the peripheral blood after treatment with ozanimod, but did not investigate the changes of leukocyte subtypes in colon mucosa and lymphatic system (ie peripheral lymph nodes. Not all patients respond to treatment with ozanimod. This non-response may be due to a mechanistic failure, where there is ongoing inflammation despite adequate drug concentrations caused by pharmacodynamic failure. The changes in leukocyte subtypes which this study investigates, could give more insight into this type of failure.

Conditions

• Ulcerative Colitis

Interventions

Type	Name	Description
DRUG	Ozanimod Oral Capsule	open label ozanimod

Timeline

• Start date: 2024-08-01
• Primary completion: 2026-03-01
• Completion: 2027-03-01
• First posted: 2024-01-03
• Last updated: 2024-09-19