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Low dose photodynamic therapy in chronic active crohn's disease: a multicenter, randomized, double-blind, placebo-controlled trial

English title Low dose photodynamic therapy in chronic active crohn's disease: a multicenter, randomized, double-blind, placebo-controlled trial
Applicant Ortner Maria-Anna E. J.
Number 112603
Funding scheme Project funding (Div. I-III)
Research institution Klinik für Gastroenterologie Universitätsspital Zürich
Institution of higher education University of Lausanne - LA
Main discipline Clinical Immunology and Immunopathology
Start/End 01.04.2006 - 31.01.2013
Approved amount 251'300.00
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All Disciplines (2)

Discipline
Clinical Immunology and Immunopathology
Immunology, Immunopathology

Keywords (5)

bakterienkolonisation in der mukosa; histologie; multizenterstudie; medizinische statistik; preparation medikament und plazebo

Lay Summary (English)

Lead
Lay summary
In Crohn’s disease (CD), one of the major forms of idiopathic, chronic inflammatory bowel disorders, inflammation is thought to result from an overwhelming and ongoing activation of the mucosal immune system, induced by the normal luminal flora in genetically susceptible individuals.Therefore, drug treatment is mainly directed at modification of the immunological response or manipulation of the enteric flora. Despite development of biological cures, therapy in CD is still unsatisfactory.
Therefore, new treatment modalities are desirable. Desired characteristics would include an inhibition of the overwhelming proinflammatory immune response, an effect on bacterial mucosal colonization, a good safety profile and the possibility to readminister treatment as often as needed.
We postulate that photodynamic therapy (PDT) fulfills these goals. PDT uses photo-physical properties of light-absorbing drugs, which accumulate in activated cells (for example activated inflammatory cells). After exposure to light, these drugs induce a variety of reactions like cell death, inhibition of proinflammatory immune messengers, and inactivation or death of several strains of bacteria. In a mouse colitis model resembling CD we were able to demonstrate that even a single «low dose » of PDT exerts a favorable effect on colitis and induces a downregulation of the proinflammatory immune response. In this model, the PDT effect correlates positively with the severity of inflammation. Furthermore PDT is safe, neither inducing local or systemic side effects.
The immediate goal of this project is to evaluate «low dose » PDT in patients with CD (specific aim 1: clinical improvement, healing of colitis, safety) and to investigate the pathophysiological mechanism of «low dose » PDT in humans (specific aim 2: downregulation of the proinflammatory immune response, decrease of mucosal bacterial colonization).
In order to evaluate the response to PDT, a multicenter, randomized, double-blind, placebo-controlled trial in patients with known CD involving the colon will be performed. Patients with moderately active disease and stable medication will be eligible for this study. Crohn’s Activity Index, Quality of Life, Endosocpic Severity Index, histological scores and adverse effects will be assessed. In order to investigate the local immunomodulatory effects and the effects on bacterial colonization, local (cytokines, apoptosis, metalloproteinases in colonic tissue) and systemic (whole blood cell synthesis of cytokines), immunological markers will be assessed.
The information gained could lead to a new therapeutic approach in CD that favorably modifies the immunologic response and inhibits mucosal bacterial colonization. Furthermore, in contrast to available drug treatment that blocks only isolated cytokines, PDT could lead to a comprehensive control of the immune response. If systemic side effects turn out to be negligible in man, PDT could be repeated as often as needed.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Cancer prevention in ulcerative colitis: long-term outcome following fluorescence-guided colonoscopy
Fusco V Ebert B Weber-Eibel J et al (2011), Cancer prevention in ulcerative colitis: long-term outcome following fluorescence-guided colonoscopy, in Inflammatory Bowel Disease, 18(3), 489-449.
Low-dose endoluminal photodynamic therapy improves murine T-cell mediated colitis. Endoscopy
Favre L Borle F Velin D et al (2011), Low-dose endoluminal photodynamic therapy improves murine T-cell mediated colitis. Endoscopy, in Endoscopy , 43(7), 604-616.
Time-gated fluorescence spectroscopy improves endoscopic detection of low-grade dysplasia in ulcerative colitis.
Ortner MA Fusco V Ebert B et al. (2010), Time-gated fluorescence spectroscopy improves endoscopic detection of low-grade dysplasia in ulcerative colitis., in Gastrointest Endosc , 71(2), 312-318.

Collaboration

Group / person Country
Types of collaboration
EPFL Lausanne Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
TechnoStat Israel (Asia)
- Publication
Universitätsklinik Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Columbia University, New York, USA. Grand Rounds Talk given at a conference 25.02.2013 New York, United States of America Ortner Maria-Anna E. J.;
CIRSE 2012 Talk given at a conference 19.09.2012 Lissabon, Portugal Ortner Maria-Anna E. J.;
Fortbildung Uniklinikum Zürich, Schweiz, . Talk given at a conference 05.10.2010 Zürich, Switzerland Ortner Maria-Anna E. J.;
UVCM Retreat 2009 Talk given at a conference 20.11.2009 Murten, Switzerland Ortner Maria-Anna E. J.;
Swiss IBD Days 2008. Talk given at a conference 04.04.2008 Posieux, Switzerland Ortner Maria-Anna E. J.; Michetti Pierre;
Klinisch-Wissenschaftliche Kolloquien, Universitätsklinik Regensburg Talk given at a conference 24.01.2008 Regensburg, Germany Ortner Maria-Anna E. J.;


Patents

Title Date Number Inventor Owner
Use of a photosensitizing agent in the treatment or prevention of an inflammation- associated disorder in the gastrointestinal tract of a mammal. 05.07.2006 PCT/IB2006/001857- WO2007/004045

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