Ulcerative Colitis Flare Clinical Trial
Official title:
The Effect of Lactobacillus Reuteri ATCC PTA 4659 in Patients With Ulcerative Colitis
Explorative investigation to study the effect of the endogenous bacterium Lactobacillus
reuteri ATCC PTA 4659 as a nutrient additive against relapse in ulcerative colitis. Forty
patients will be studied with a randomized parallel design over one year. Patients with
established treatment against relapse of ulcerative colitis with mesalazine ≤4 grams will be
requested to participate in the study, allocated to 20 patients with placebo and 20 with
active treatment L. reuteri as an "add-on". Inklusion: 18-80 years of age, ≥1 relapse with
bleeding during previous 12 months with a disease activity Mayo Clinical Score ≤2, treatment
with mesalazine ≤4,0 g daily. Exklusion: >80 years of age, no registered bleeding during
recent 12 months, on-going steroid treatment, immunosuppressives, biologics or adhesion
inhibitors, antibiotics or other clinical trial. behandling med probiotika. Disease
monitoring will be done with:
Time to disease relapse with macroscopic bleeding and Mayo score ≥5, blood chemistry and CRP,
lipopolysaccharides and gut permeability, fecal calprotectin, and short health scale at 4
weeks, 26 weeks and 52 weeks.
Research question To study whether dietary supplementation with L. reuteri ATCC PTA 4659
(Lr4659) is safe and can reduce the relapse rate and have a positive effect in patients with
ulcerative colitis (UC).
Lr4659 is a naturally occurring strain of human origin. It is a typical member of the L.
reuteri species, with typical sugar fermentation patterns, reuterin production and growth
characteristics. Identification using 16SrRNA gene analysis shows that it has 99% similarity
with the type strain of L. reuteri thus confirming that it belongs to this well-known and
well-studied species that is considered safe for human consumption. In vitro studies indicate
that this strain has strong tolerance to acid environments, as do many other L. reuteri
strains and that it has the unusual ability to interfere with TNFalpha mediated propagation
of inflammatory responses in human macrophages.
Treatment with the probiotic bacterium L. reuteri has been shown to prevent dextran sodium
sulfate (DSS)-induced colitis in rats. During DSS-induced colitis, the number of bacteria in
the inner firmly-adherent mucus layer increased and bacterial composition of the two layers
no longer differed. However, L. reuteri decreased the bacterial translocation from the
intestine to mesenteric lymph nodes during DSS treatment, which might be an important part of
the mechanisms by which L. reuteri ameliorates DSS-induced colitis in rats.
Study design This is a double-blind randomized clinical trial. Randomization will be done to
either mesalazine plus Lr4659, or to mesalazine plus placebo for a continuous treatment until
new bleeding episode or a maximum of 52 weeks.
Forty patients with UC in remission, medicated with <4 g mesalazine and aged over 18 years
will be recruited. After written consent to the study the subjects in whom the eligibility
criteria are confirmed the subjects will be randomized to receive either 2 daily doses of
Lr4659 (n=15) or the corresponding placebo. The total length of study treatment is 52 weeks.
Concomitant treatment During the period of the study, the subjects will refrain from
ingestion of any kind of probiotic or bacterial preparation.
The objective is to determine whether dietary supplementation with Lr4659 is able to: Prolong
time in remission and Time from last bleeding episode until re-bleeding, Time from start of
study treatment until re-bleeding, Reduce Mayo score reduction by at least 50%, Reduce
f-calprotectin, Reduce recovered sucralose in the sucralose gut permeability test, Reduce
zonulin expression from gut mucosa, Impact microflora composition
Study Product and Dosage Lr4659, consisting of L. reuteri ATCC PTA 4659 will be delivered at
a dose of 5x108 colony forming units (CFU) as a powder in capsules. One dose is to be taken
in the morning and one in the evening yielding a total daily dose of 1x109 CFU/day. Placebo
capsules are identical to Lr4659 except for the active ingredient. The study products will be
taken daily throughout the entire 52-week study-period.
Inclusion criteria for study: UC confirmed by biopsy, Mayo full score < 2, Total or
left-sided UC, Stable diagnose of UC >1 year, History of more than 1 yearly recurrence,
Current remission period exceeding 2 months, 18-80 years of age, Baseline 5-ASA ≤4g daily,
Mentally fit to participate, Informed consent obtained Exclusion criteria: Crohn's disease,
Ulcerative proctitis, Infective colitis, Liver disease, Current use of probiotics, Current
medication acetylsalicylic acid (ASA), non-steroidal antiinflammatory drugs (NSAID),
corticosteroids, anticoagulants, serotonin-selective re-uptake inhibitors (SSRI),
serotonin-noradrenaline re-uptake inhibitors (SNRI), azathioprine (AZA), 6-mercaptopurin
(6-MP), thioguanin (TG), anti-TNF-alpha biologicals, Participation in other clinical trials
Analyses Evaluation of the clinical Mayo score will be done by ocular inspection and
immediate recording in the CRF.
C-reactive protein (CRP) will be locally analysed according to clinical routine by Department
of clinical chemistry, Uppsala University Hospital.
Fecal calprotectin will be analysed according to local routines (Bühlmann, Schönenbuch,
Switzerland) by Department of clinical chemistry, Uppsala University Hospital).
"Gut" permeability focuses on colonic permeability as studied with recovery of different
sugar components in the urine. 24-hour urine will be analysed by an in-house high performance
liquid chromatography (HPLC) method by GastroLab, Uppsala University Hospital.
Fecal microbiology, alfa-diversity, beta-diversity
Expected findings: Prolonged interval to next flare of UC with rectal bleeding. Reduced
calprotectin and CRP levels.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT05466890 -
Phase 2a To Evaluate PL-8177 in Subjects With Active Ulcerative Colitis (UC)
|
Phase 2 | |
| Recruiting |
NCT05680883 -
Local and Systemic Immunoprofiling of Patients Diagnosed With Ulcerative Colitis
|
||
| Not yet recruiting |
NCT04276740 -
MARVEL: Mitochondrial Anti-oxidant Therapy to Resolve Inflammation in Ulcerative Colitis
|
Phase 2 | |
| Not yet recruiting |
NCT04926103 -
Screening Donors, Fecal Microbiota Transplant Program in Ulcerative Colitis
|
N/A | |
| Recruiting |
NCT05998213 -
Transfer of Feces in Ulcerative Colitis 2
|
Phase 2 |