Tocilizumab for Painful Chronic Pancreatitis (TOPAC trial): Protocol for a phase 2 randomized, placebo-controlled, double-blind, investigator-initiated trial.

IF 2.8 2区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Pancreatology Pub Date : 2025-03-04 DOI:10.1016/j.pan.2025.03.001

Rasmus Hagn-Meincke, Jens Brøndum Frøkjær, Asbjørn Mohr Drewes, Charlotte Henneberg Holmboe, Klaus Krogh, Rasmus Bach Nedergaard, Line Davidsen, Tina Okdahl, Ingfrid Salvesen Haldorsen, Walter Park, Bent Winding Deleuran, Søren Schou Olesen

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引用次数: 0

Abstract

Background: Chronic pancreatitis (CP) is a fibro-inflammatory disease that damages the pancreas, leading to severe abdominal pain and metabolic complications. Activated macrophages and pancreatic stellate cells drive CP progression, and their activity is regulated by complex immune signals, including interleukin-6 (IL-6). Preclinical studies suggest that blocking IL-6 signalling may have pain-relieving effects in CP. Based on these findings, we hypothesise that tocilizumab, an anti-IL-6 receptor antibody, will reduce abdominal pain and improve physical functioning and quality of life in patients with CP. Additionally, we expect tocilizumab to decrease pancreatic inflammation, fibrosis, and systemic inflammation, as well as normalise pain processing.

Methods: The TOPAC trial is a phase 2, randomised, placebo-controlled, double-blinded, investigator-initiated trial conducted at Aalborg University Hospital, Denmark. Patients with painful CP and suspicion of sustained pancreatic inflammation (n = 36) will be randomised (1:1) to receive intravenous tocilizumab (8 mg/kg) or a corresponding placebo every 4 weeks for 24 weeks. The primary endpoint is the difference between the two groups in the change of the Comprehensive Pain Assessment Tool Short Form (COMPAT-SF) score from baseline to 24 weeks. Secondary outcomes include questionnaires focused on quality of life, physical/daily functioning, and the severity of pain and its impact on functioning. Additionally, safety is a key secondary endpoint. Exploratory outcomes include soluble biomarkers of inflammation and fibrosis, multiparametric pancreatic magnetic resonance imaging, quantitative sensory testing and neurophysiological measurements of the pain processing.

Conclusions: This placebo-controlled clinical trial aims to study the potential clinical benefits of blocking IL-6 signalling in painful CP.

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来源期刊

Pancreatology 医学-胃肠肝病学

CiteScore

7.20

自引率

5.60%

发文量

194

审稿时长

44 days

期刊介绍： Pancreatology is the official journal of the International Association of Pancreatology (IAP), the European Pancreatic Club (EPC) and several national societies and study groups around the world. Dedicated to the understanding and treatment of exocrine as well as endocrine pancreatic disease, this multidisciplinary periodical publishes original basic, translational and clinical pancreatic research from a range of fields including gastroenterology, oncology, surgery, pharmacology, cellular and molecular biology as well as endocrinology, immunology and epidemiology. Readers can expect to gain new insights into pancreatic physiology and into the pathogenesis, diagnosis, therapeutic approaches and prognosis of pancreatic diseases. The journal features original articles, case reports, consensus guidelines and topical, cutting edge reviews, thus representing a source of valuable, novel information for clinical and basic researchers alike.