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Multi-center, multi-national, double-blind, placebo controlled study to evaluate the efficacy and safety of an anthocyanin-rich extract (ACRE) in moderately active ulcerative colitis

English title Multi-center, multi-national, double-blind, placebo controlled study to evaluate the efficacy and safety of an anthocyanin-rich extract (ACRE) in moderately active ulcerative colitis
Applicant Rogler Gerhard
Number 166844
Funding scheme Investigator Initiated Clinical Trials (IICT)
Research institution Klinik für Gastroenterologie und Hepatologie Departement Innere Medizin Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Internal Medicine
Start/End 01.06.2016 - 28.02.2022
Approved amount 1'021'317.00
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All Disciplines (2)

Discipline
Internal Medicine
Clinical Pharmacology

Keywords (6)

multicenter; placebo controlled; inflammation; clinical study; ulcerative colitis; anthocyanins

Lay Summary (German)

Lead
Eine klinische Studie zur Wirksamkeit von Anthocyanen (Pflanzenextrakten) bei Colitis ulcerosa Patienten
Lay summary
Die Colitis ulcerosa (UC) ist eine chronische entzündliche Darmerkrankung, die vor allem junge Erwachsene betrifft, durch eine Entzündung des Dickdarms gekennzeichnet ist und zu schwerem, oft blutigem Durchfall und starken Bauchkrämpfen führt. Die Lebensqualität ist beeinträchtigt, eine Heilung der Erkrankung ist nicht möglich. Bei mehr als mehr als 10% der Patienten muss eine operative Dickdarmentfernung durchgeführt werden, weil die medikamentöse Therapie nicht erfolgreich ist.
Zur Therapie der schweren Colitis werden vielfach Immunhemmer eingesetzt. Sie bergen ein erhebliches Risiko von Nebenwirkungen. Daher hat die Entwicklung von zusätzlichen Behandlungsmöglichkeiten, mit günstigem Kosten-Nutzen-Verhältnis und günstigem Nebenwirkungsprofil eine grosse Bedeutung
In den letzten Jahren fand eine Gruppe von natürlichen chemischen Verbindungen ein steigendes Interesse, die sogenannten "Flavonoide". Sie zeigen positive Auswirkungen auf z.B. Herz-Kreislauf-Erkrankungen und Krebs. Anthocyane - ein Bestandteil dieser Flavonoide - sind reichlich in roten, blauen und schwarzen Beeren vorhanden. Eine positive Wirkung von Anthocyanen in Colitis-Tiermodellen wurde gezeigt. Zudem testeten wir bereits in einer kleinen Pilotstudie bei 13 Patienten mit Colitis die Wirkung von Anthocyanen. Während sechs Wochen erhielten die Patienten täglich einen Anthocyan-reichen Extrakt aus Heidelbeeren. Bei 10 der 13 Patienten wurde die Darmentzündung deutlich besser. Nebenwirkungen wurden nicht beobachtet, so dass Anthocyane bei Colitis ulcerosa eine nebenwirkungsarme Behandlungsalternative darstellen könnten. Obwohl unsere bisherigen  Ergebnisse vielversprechend sind, müssen sie in einer größeren Studie bestätigt werden. Wir planen daher eine multizentrische, multinationale, doppelblinde, Placebo-kontrollierte klinische Studie, um die Wirksamkeit, Sicherheit und Verträglichkeit eines Anthocyan-reichen Extrakts (ACRE) bei 112 Patienten mit mäßig aktiver Colitis ulcerosa zu untersuchen.
Direct link to Lay Summary Last update: 10.06.2016

Responsible applicant and co-applicants

Employees

Project partner

Collaboration

Group / person Country
Types of collaboration
Luc Biedermann, Dr. med., Oberarzt, Division of Gastroenterology, University Hospital Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Petr Hruz, PD Dr., Leitender Arzt, Division of Gastroenterology, University Hospital of Basel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Jan Borovicka, Prof. Dr. med.; Leitender Arzt, Division of Gastroenterology KSSG St. Gallen Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Florian Froehlich, Prof. Dr. med., Private Practice, Porrentruy; Email: florian.froehlich@bluewin.ch Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Marc Girardin, Dr. med., Gastroenterology FMH; Associate Physician HUG and Private Practice Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Alain Schoepfer, PD Dr. med.; Division of Gastroenterology , University Hospital Lausanne/CHUV Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Jost Langhorst, Prof. Dr. med. Integrative Gastroenterology, Kliniken Essen-Mitte, Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Andrew J. Macpherson, Prof. Dr. med.; Director of Gastroenterology, University Hospital of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Frank Seibold, Prof. Dr. med.; Seibold & Partner und Crohn-Colitis-Center, Berne and Fribourg Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Associated projects

Number Title Start Funding scheme
148422 Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS) 01.04.2014 Cohort Studies Large
170109 Dietary nanoparticles and their impact on Inflammatory Bowel Disease pathogenesis - Large Nested Project within the SWISS IBD Cohort Study 01.10.2016 Project funding (special)
172870 The role of pH sensing G-protein coupled receptors for intestinal inflammation and fibrosis 01.05.2017 Project funding (Div. I-III)

Abstract

Ulcerative colitis (UC) is a lifelong, chronic inflammatory bowel disease (IBD) affecting mainly young adults, characterized by inflammation of the large intestine in various extensions. Severe diarrhea, often bloody, as well as abdominal cramps are among the most common symptoms of UC. Although the clinical course is variable, most patients suffer from recurrent flares and an unpredictable disease course. Quality of life may be severely impacted by persistent, frequent, repeated or waxing and waning symptoms. There is no cure of the disease. About two thirds of all UC patients with moderate disease activity can be successfully treated with mesalamine (5-ASA). However, the patients that do not achieve a sufficient response remain a clinical challenge and more than 10% of all patients have to undergo colectomy. Although there are a number of potential effective drugs to be used in UC, the overall profile of those is far from being ideal: They harbor a considerable risk of short- and long-term toxicity and side effects. Moreover, the annual costs of newer treatment options (such as biologicals) are high. Most importantly, even the newest treatments only work in small proportions of UC patients. Thus it becomes obvious, that the development of additional medical treatment options, with favorable cost-benefit ratio and salutary side-effect profile clearly represents an unmet clinical need in UC. A recent study on the effect of curcuma (an Indian spice) in UC patients proves that this is possible (1).In recent years there has been a rising interest in a group of natural chemical compounds, the polyphenols, and especially in a subgroup, the flavonoids, due to their beneficial effects on various aspects of human health, including cardiovascular disease and cancer. Anthocyanins (ACs) - a fraction of these food flavonoids - are abundant in red, blue and black berries, but also occur in red wine and certain vegetables. Various research groups including ours could identify a beneficial effect of ACs in animal models of colitis (one of the most stable we have observed so far) (2). In view of these replicated promising results we were the first to test the potential of ACs in a small pilot trial in 13 patients with UC (3). During six weeks, patients received a daily anthocyanin-rich extract from bilberries. Strikingly, disease activity, endoscopic findings as well as objective parameters, such as the fecal inflammatory activity (assessed by calprotectin) or the extent of inflammation in mucosal biopsies showed a clear improvement. Side effects were not observed. Based on these data we believe that ACs may provide an important and effective adjunctive treatment option in UC with very few - if any at all - side effects (4).Although these results are highly promising, they need to be confirmed in a larger trial. Placebo control, randomization and full blinding of the patients will be mandatory. Thus, to confirm these promising results we plan to perform a multi-center, multi-national, double-blind, placebo controlled, parallel group study to evaluate the efficacy, safety and tolerability of an anthocyanin-rich extract (ACRE) in subjects with moderately active 5-ASA-refractory UC including 112 UC-patients in IBD treatment centers in Switzerland (where we have the established IBDnet and Swiss IBD Cohort Study structure with outstanding clinical trial experience; see http://www.ibdnet.ch), Germany and Ireland. No major pharmaceutical company is interested in sponsoring such costly trials of a natural product were no IP can be protected. We will be supported by the Clinical Trials Center (CTC) of the UZH.
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