A Phase 1/2 interventional study of GM-CSF, fosfomycin and metronidazole in Pouchitis, sponsored by Zealand University Hospital. Status unknown at 1 site in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-01-26.
Sponsored by Zealand University Hospital · Phase 1/2, Interventional, and Treatment
This study will examine whether the application of GM-CSF, fosfomycin and metronidazole locally in the pouch is safe and effective in the treatment of pouchitis for patients with ulcerative colitis, and whether treatment changes the microbiome of the pouch.
A definitive cure for patients with treatment-refractory ulcerative colitis is proctocolectomy with IPAA (restorative ileal pouch anal anastomosis). Up to 50% of all patients develop "pouchitis" within the first five years after surgery, an inflammatory condition that is as yet poorly understood and without official consensus on treatment. Treatment modalities include oral antibiotics as well as immunomodulators, steroids, probiotics and biological agents, but up to 20% of these patients develop chronic, treatment-resistant pouchitis, which can result in pouch failure and the need for reoperation with the possible creation of an ileostomy.
The etiology of pouchitis is thought to be similar to other inflammatory bowel diseases, in that genetic and bacterial factors, a compromised gastrointestinal barrier and immunological components seem to play a role. Its pathogenetic mechanisms seem to mimic Crohn's disease, in which smaller studies have shown some effect of systemically administered GM-CSF (granulocyte-macrophage colony stimulating factor) on the gut macrophage function in clearing microorganisms and maintaining the mucosal barrier.
The investigators hypothesize that GM-CSF will have an effect in the treatment of pouchitis because of its similarity to that of Crohn's disease. In order to maximize effect on the inflamed mucosa and minimize systemic side effects, the study drug will be administered locally in the pouch. In a safety and proof-of-concept intervention study, 50 µg GM-CSF will be combined with 400 mg Fosfomycin and 100 mg Metronidazole, to target both the suspected immunological as well as the bacterial role in the pathogenesis of pouchitis.
The effect on the pouch will be assessed endoscopically and histologically by taking biopsies that will also be examined for changes in the microbiome. Trial participants will be clinically examined and have blood samples taken to monitor for adverse reactions. The primary outcome measure will be an assessment of adverse reactions and tolerability of the drug. Secondary outcome measures will be a change in the pouchitis disease activity index (PDAI), a change in the microbial diversity, and a change in inflammatory markers.
This study is based on a non-randomized trial design with an open-label single group assignment.
Phase I The tolerability of treatment will be tested on 6 trial participants with pouchitis with a single dose of the combined medication applied endoscopically in the pouch. Endoscopy with the taking of biopsies will be performed before and one week after administration of the medication, as well as blood samples before and after the medication. After the follow-up endoscopy, the trial participant will receive standard oral metronidazole or ciprofloxacin treatment for 10 days.
Phase II Depending on effect of the first study, the second study plans for the treatment of 12 trial participants. Endoscopy with biopsies will be conducted with the first application of the study drug combination in the pouch, and afterward a daily dosage for another 6 days. Clinical and endoscopic control after 14 days with blood samples and biopsies will be done. After the follow-up endoscopy, the trial participant will receive standard oral metronidazole or ciprofloxacin treatment for 10 days.
50 studies on the registry are indexed under Pouchitis; 12 are open to participants now.
This study's planned enrollment of 18 is close to the median of 20 across 42 interventional studies indexed under Pouchitis.
Browse Pouchitis studies →Zealand University Hospital is the lead sponsor of 236 studies on the registry; 50 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ASA physical status
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Local administration of 50 micrograms GM-CSF, 400 milligrams fosfomycin and 100 milligrams metronidazole in the pouch. In a Phase A of the trial, this will be applied as a single dose during endoscopy of the pouch. In Phase B of the trial, this will be applied as a first dose during endoscopy of the pouch, followed by 6 further daily doses for a total of 7 doses.
Drug: GM-CSF, fosfomycin and metronidazole
Drug pages: Granulocyte-Macrophage Colony-Stimulating Factor · Fosfomycin · Metronidazole
GM-CSF 50 micrograms Fosfomycin 400 milligrams Metronidazole 100 milligrams applied as a gel in the pouch
Also known as: GM-CSF, Fosfomycin, Metronidazole
Phase 1: safety study, Determine serious adverse reactions or adverse reactions from the application of GM-CSF, metronidazole and fosfomycin in the pouch
Incidence of Treatment-Emergent Adverse Events
Time frame: 30 days after first application of study drug
Phase 2: Proof of concept study, Change in the pouchitis disease activity index (PDAI)
A decrease of 3 points or more will be determined as an improvement in PDAI from before application of the study drug to 7 days after application of the study drug. Between 0-18 points can be given, with a score of 7 or higher indicating pouchitis.
Time frame: 14 days after first application of the study drug
Phase 1: Change in the pouchitis disease activity index (PDAI)
A decrease of 3 points or more will be determined as an improvement in PDAI from before application of the study drug to 7 days after application of the study drug. Between 0-18 points can be given, with a score of 7 or higher indicating pouchitis.
Time frame: Within 7 days after application of the study drug
Phase 1: Number of trial participants with a change in median white blood cells after treatment
Change in median white blood cells (numbers × 10\^9/L)
Time frame: Within 7 days after application of the study drug
Phase 1: Number of trial participants with a change in median CRP after treatment
Change in median CRP (mg/L)
Time frame: Within 7 days after application of the study drug
Phase 1: Number of trial participants with a change in median creatinine after treatment
Change in median creatinine (µmol/L)
Time frame: Within 7 days after application of the study drug
Phase 1: Number of trial participants with a change in median liver enzymes after treatment
Change in median liver enzymes (ALAT, alanine-aminotransferase in U/L)
Time frame: Within 7 days after application of the study drug
Phase 1: Change in microbial diversity in the pouch using 16S rRNA sequencing
A qualitative assessment of the microbial diversity of the mucosa of the pouch by determining species names and distribution quantity using 16S rRNA sequencing.
Time frame: Within 7 days after application of the study drug
Phase 2: Change in the clinical, endoscopic or histological PDAI
A decrease of 3 points or more will be determined as an improvement in PDAI individually for clinical (0-6 points), endoscopic (0-6 points) and histological (0-6 points) PDAI.
Time frame: 14 days after first application of the study drug
Phase 2: Number of trial participants with a change in median white blood cells after treatment
Change in median white blood cells (numbers × 10\^9/L)
Time frame: 14 days after first application of the study drug
Phase 2: Number of trial participants with a change in median CRP after treatment
Change in median CRP (mg/L)
Time frame: 14 days after first application of the study drug
Phase 2: Number of trial participants with a change in median creatinine after treatment
Change in median creatinine (µmol/L)
Time frame: 14 days after first application of the study drug
Phase 2: Number of trial participants with a change in median liver enzymes after treatment
Change in median liver enzymes (ALAT, alanine-aminotransferase in U/L)
Time frame: 14 days after first application of the study drug
Phase 2: Change in microbial diversity in the pouch using 16S rRNA sequencing
A qualitative assessment of the microbial diversity of the mucosa of the pouch by determining species names and distribution quantity using 16S rRNA sequencing.
Time frame: 14 days after first application of the study drug
Phase 2: Determine serious adverse reactions or adverse reactions from the application of GM-CSF, metronidazole and fosfomycin in the pouch
Incidence of Treatment-Emergent Adverse Events
Time frame: 37 days after first application of the study drug
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Started Sep 2021 (actual). Primary completion is estimated for Dec 2023, 27 months after the start.
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This study is status unknown, as verified in Jan 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Granulocyte-Macrophage Colony-Stimulating Factor · Fosfomycin · Metronidazole