A combined treatment with GM-CSF, fosfomycin and metronidazole for pouchitis in ulcerative colitis patients after restorative ileal pouch anal anastomosis surgery. A clinical safety and proof-of-concept study

Phase 1/2

Not yet recruiting

• Conditions: Pouchitis

• Registration Number: 2024-517764-38-00
• Lead Sponsor: Region Sjaelland, Reponex Pharmaceuticals A/S

Brief Summary

We aim to investigate whether GM-CSF in combination with metronidazole and fosfomycin, applied topically in the pouch, can be used in patients with pouchitis. As pouchitis seems to mimic Crohn’s disease, and responds to therapy used in Crohn’s disease, we suspect that this combination therapy can target the bacterial dysbiosis and inadequate immune response in pouchitis.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-09-27
• Last Update Posted: 2024-11-14

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 18

Inclusion Criteria

• Of any gender • Over 18 years of age • Have a previous diagnosis of ulcerative colitis • Have had IPAA surgery, and • Have been diagnosed with pouchitis • Be able to understand and complete study procedures as determined by the investigator • Be able to speak either Danish or English • Be able to comply with study procedures for the length of the study • Use a highly effective contraception method for the duration of the trial (until day 30 in Phase I and until day 37 in Phase II), such as implants, injectables, oral contraceptives, IUD (intrauterine device), sexual abstinence or vasectomized partner.

Exclusion Criteria

• Patients with a previous allergic reaction to GM-CSF, metronidazole or fosfomycin • Patients who are currently under antibiotic treatment or have received antibiotic treatment within the past 30 days • Patients currently pregnant or breastfeeding • Patients with ASA IV classification (American Society of Anesthesiologists physical status classification) • Patients with severe pulmonary disease • Patients with autoimmune thrombocytopenia • Patients with severe renal impairment (eGFR < 40 ml/min) • Patients with alcohol use disorder or history of drug abuse • Patients currently in treatment for any malignant or hematological disease • Patients with a previous history of cancer will be excluded from the study (except for patients with well-treated and stabile cancer after a control period of more than two years). • Patients with anticipated compliance problems as determined by the investigator

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in the pouchitis disease activity index (PDAI		Change in the pouchitis disease activity index (PDAI

Secondary Outcome Measures

Name	Time	Method
Change in the clinical, endoscopic or histological PDAI		Change in the clinical, endoscopic or histological PDAI
Change in median WBC, CRP, creatinine and liver enzymes from before application of the study drug to 7 days after application of the study drug		Change in median WBC, CRP, creatinine and liver enzymes from before application of the study drug to 7 days after application of the study drug
Change in microbial diversity in the pouch using 16S rRNA sequencing from before application of the study drug to 7 days after application of the study drug		Change in microbial diversity in the pouch using 16S rRNA sequencing from before application of the study drug to 7 days after application of the study drug
Safety: Determine serious adverse reactions or adverse reactions from the application of GM-CSF, metronidazole and fosfomycin in the pouch		Safety: Determine serious adverse reactions or adverse reactions from the application of GM-CSF, metronidazole and fosfomycin in the pouch
Assess the modulation of dendritic cells and inflammatory mechanisms using Nanostring nCounter analysis through mRNA expression and flow cytometry		Assess the modulation of dendritic cells and inflammatory mechanisms using Nanostring nCounter analysis through mRNA expression and flow cytometry

Trial Locations

Locations (1)

Region Sjaelland; 🇩🇰 Koege, Denmark

Region Sjaelland

🇩🇰Koege, Denmark

Ismail Gögenur

Site contact

47323011

igo@regionsjaelland.dk