E-Thesis 153 views
Faecal Microbiota Transplant in Ulcerative Colitis (FMTUC) A Randomised Clinical Trial Feasibility Study / MAKI JITSUMURA
Swansea University Author: MAKI JITSUMURA
DOI (Published version): 10.23889/SUthesis.61587
Abstract
Aims Restoring gut dysbiosis with faecal microbiota transplant (FMT) is of increasing interest as a therapeutic option in the management of Ulcerative colitis (UC). The aims of this thesis are to conduct a review of endpoints in UC clinical trials, to conduct a Phase II feasibility study to estimate...
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Swansea
2022
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| Institution: | Swansea University |
| Degree level: | Doctoral |
| Degree name: | M.D |
| Supervisor: | Davies, Angharad ; Row, Paula |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa61587 |
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| Abstract: |
Aims Restoring gut dysbiosis with faecal microbiota transplant (FMT) is of increasing interest as a therapeutic option in the management of Ulcerative colitis (UC). The aims of this thesis are to conduct a review of endpoints in UC clinical trials, to conduct a Phase II feasibility study to estimate the magnitude of treatment response to FMT in treatment-naïve patients with UC, to evaluate recruitment rates and to determine optimal study conditions and choice of endpoints for the phase III FMTUC study. Methods Narrative Review: The current consensus on endpoints in UC clinical trials were systematically reviewed using two indices: the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and the Ulcerative Colitis Disease Activity Index (UCDAI). FMTUC: Treatment-naive UC subjects were randomised to i) single enema, ii) five daily enemas or iii) control group. All groups received bowel decontamination prior to the FMT interventions. Subjects were assessed using qualitative assessment tools, blood tests, 16S RNA sequencing on faecal samples for 12 weeks. Endoscopic and histological assessments were also performed at baseline and week 12. The paired primary endpoints were remission of UC and successful engraftment of donor faecal microbiota at 12 weeks. Clinical remission was defined as Mayo score ≤ 2 with an endoscopic Mayo score of 0.Conclusions Eighteen patients were recruited between July 2016 and February 2020 and five achieved clinical remission. Clinical remission was more frequently observed among subjects with mild-moderate disease (P = 0.173). No correlations between FMT dose, frequency and clinical response were observed. The 16S evaluation demonstrated the altering the faecal microbiota after the interventions. This study also showed an inverse correlation between IL-10 and the severity of UC. The narrative review highlighted the importance of urgent universal consensus on both clinical remission and validated outcome tools, such as the UCEIS. This feasibility study of FMT successfully demonstrated potential for employing this method in the management of UC. |
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| Keywords: |
Faecal Microbiota Transplant, FMT, Ulcerative Colitis, FMTUC |
| College: |
Faculty of Medicine, Health and Life Sciences |