Ignite Creation Date:
2025-12-24 @ 9:43 PM
Ignite Modification Date:
2025-12-25 @ 7:24 PM
Study NCT ID:
NCT04979832
Status:
UNKNOWN
Last Update Posted:
2023-01-26
First Post:
2021-06-30
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
GM-CSF, Fosfomycin and Metronidazole for Pouchitis in Ulcerative Colitis Patients After Restorative IPAA Surgery
Sponsor:
Zealand University Hospital
Organization:
Study Overview
Official Title:
A Combined Treatment With GM-CSF, Fosfomycin and Metronidazole for Pouchitis in Ulcerative Colitis Patients After Restorative Ileal Pouch Anal Anastomosis Surgery
Status:
UNKNOWN
Status Verified Date:
2023-01
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
Detailed Description:
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2020-000609-10 | EUDRACT_NUMBER | None | View |