Matches in SemOpenAlex for { <https://semopenalex.org/work/W4236020781> ?p ?o ?g. }
Showing items 1 to 82 of
82
with 100 items per page.
- W4236020781 endingPage "S6" @default.
- W4236020781 startingPage "S5" @default.
- W4236020781 abstract "Abstract Background Emerging evidence has demonstrated that protein misfolding in the endoplasmic reticulum (ER), i.e., ER stress, plays fundamental roles in IBD development in humans. Patients with active Crohn’s disease and ulcerative colitis exhibit signs of ER stress in their ileal and/or colonic epithelium. Human genetic studies of IBD have identified primary genetic abnormalities in several genes that encode proteins associated with ER stress. We recently reported that oral delivery of tauroursodeoxycholic acid (TUDCA), a naturally occurring bile salt proven to reduce ER stress both in vitro and in vivo, dramatically decreases the clinical, histological and biochemical signs of inflammation in four different IBD mouse models through reducing ER stress in colonic epithelial cells. Aim Based on this, our aim was to test the efficacy and safety of TUDCA in an open label, Phase I trial for patients with symptomatic ulcerative colitis. Methods TUDCA was administered at 2000 mg divided TID for 6 weeks. Baseline and 6 week colonoscopy/flexible sigmoidoscopy with biopsy was performed. Outcome measures include safety, tolerability, Mayo score, and change in markers of ER stress from colon biopsies. Results To date, complete data is available on 9 of a planned 12 patients. TUDCA was well tolerated and safe with no Grade 3 or greater CTCAE adverse events and no Serious Adverse Events. A significant reduction of 4.6 points on the complete Mayo score was observed from baseline to week 6 (Avg. 8.6 ± 2.5 → 4.00 ± 2.7, P=0.004) with 100% of patients seeing a decrease. Clinical remission, clinical response and mucosal healing were observed in 22%, 67% and 56% respectively. Fecal calprotectin decreased in 67% of patients. As diarrhea can be a side effect of TUDCA treatment at these doses, we also assessed the Partial Mayo Score at two weeks after completion of the trial (8 weeks from baseline). At this time point the Partial Mayo Score significantly decreased by 3.8 points (Avg. 6.2 ± 2.1 → 2.4 ± 1.9, P=0.004) with 67% achieving clinical response and 56% remission. The Robarts Histopathology Index decreased in 8 of 9 patients with a mean reduction of 2.67 points (Avg. 6.4 ± 3.2 → 3.8 ± 2.9, P=0.003). Total serum bile acid profiles changed, but not significantly so, from Wk0 to Wk6. ER stress markers Bip, eIF2a and p-eIF2a were increased in inflamed colon tissue and were lowered post TUDCA treatment in a subset of patients. Conclusions Preliminary results from a Phase I clinical trial demonstrate that the dietary supplement TUDCA is safe, well tolerated and is associated with significant clinical improvement in a majority of patients with moderate to severely active ulcerative colitis. Mucosal healing and reductions in markers of ER stress were observed in a subset of patients. Study completion and analysis of gene expression and microbiome are underway." @default.
- W4236020781 created "2022-05-12" @default.
- W4236020781 creator A5009302642 @default.
- W4236020781 creator A5010181925 @default.
- W4236020781 creator A5015378855 @default.
- W4236020781 creator A5023095216 @default.
- W4236020781 creator A5027160505 @default.
- W4236020781 creator A5030317845 @default.
- W4236020781 creator A5047477696 @default.
- W4236020781 creator A5084080590 @default.
- W4236020781 creator A5090691804 @default.
- W4236020781 date "2021-01-01" @default.
- W4236020781 modified "2023-09-26" @default.
- W4236020781 title "A TRANSLATIONAL PHASE I STUDY OF TAUROURSODEOXYCHOLIC ACID (TUDCA) TO REDUCE SYMPTOMS AND ER STRESS IN ACTIVE ULCERATIVE COLITIS" @default.
- W4236020781 doi "https://doi.org/10.1093/ibd/izaa347.013" @default.
- W4236020781 hasPublicationYear "2021" @default.
- W4236020781 type Work @default.
- W4236020781 citedByCount "0" @default.
- W4236020781 crossrefType "journal-article" @default.
- W4236020781 hasAuthorship W4236020781A5009302642 @default.
- W4236020781 hasAuthorship W4236020781A5010181925 @default.
- W4236020781 hasAuthorship W4236020781A5015378855 @default.
- W4236020781 hasAuthorship W4236020781A5023095216 @default.
- W4236020781 hasAuthorship W4236020781A5027160505 @default.
- W4236020781 hasAuthorship W4236020781A5030317845 @default.
- W4236020781 hasAuthorship W4236020781A5047477696 @default.
- W4236020781 hasAuthorship W4236020781A5084080590 @default.
- W4236020781 hasAuthorship W4236020781A5090691804 @default.
- W4236020781 hasConcept C121608353 @default.
- W4236020781 hasConcept C126322002 @default.
- W4236020781 hasConcept C139447449 @default.
- W4236020781 hasConcept C158617107 @default.
- W4236020781 hasConcept C197934379 @default.
- W4236020781 hasConcept C2775862500 @default.
- W4236020781 hasConcept C2777422422 @default.
- W4236020781 hasConcept C2778260677 @default.
- W4236020781 hasConcept C2778375690 @default.
- W4236020781 hasConcept C2778435480 @default.
- W4236020781 hasConcept C2779134260 @default.
- W4236020781 hasConcept C2780479503 @default.
- W4236020781 hasConcept C526805850 @default.
- W4236020781 hasConcept C55493867 @default.
- W4236020781 hasConcept C71924100 @default.
- W4236020781 hasConcept C86803240 @default.
- W4236020781 hasConcept C90924648 @default.
- W4236020781 hasConceptScore W4236020781C121608353 @default.
- W4236020781 hasConceptScore W4236020781C126322002 @default.
- W4236020781 hasConceptScore W4236020781C139447449 @default.
- W4236020781 hasConceptScore W4236020781C158617107 @default.
- W4236020781 hasConceptScore W4236020781C197934379 @default.
- W4236020781 hasConceptScore W4236020781C2775862500 @default.
- W4236020781 hasConceptScore W4236020781C2777422422 @default.
- W4236020781 hasConceptScore W4236020781C2778260677 @default.
- W4236020781 hasConceptScore W4236020781C2778375690 @default.
- W4236020781 hasConceptScore W4236020781C2778435480 @default.
- W4236020781 hasConceptScore W4236020781C2779134260 @default.
- W4236020781 hasConceptScore W4236020781C2780479503 @default.
- W4236020781 hasConceptScore W4236020781C526805850 @default.
- W4236020781 hasConceptScore W4236020781C55493867 @default.
- W4236020781 hasConceptScore W4236020781C71924100 @default.
- W4236020781 hasConceptScore W4236020781C86803240 @default.
- W4236020781 hasConceptScore W4236020781C90924648 @default.
- W4236020781 hasIssue "Supplement_1" @default.
- W4236020781 hasLocation W42360207811 @default.
- W4236020781 hasOpenAccess W4236020781 @default.
- W4236020781 hasPrimaryLocation W42360207811 @default.
- W4236020781 hasRelatedWork W1975032444 @default.
- W4236020781 hasRelatedWork W2049047934 @default.
- W4236020781 hasRelatedWork W2090292636 @default.
- W4236020781 hasRelatedWork W2105447106 @default.
- W4236020781 hasRelatedWork W2326791703 @default.
- W4236020781 hasRelatedWork W2765902450 @default.
- W4236020781 hasRelatedWork W2922011006 @default.
- W4236020781 hasRelatedWork W2963825579 @default.
- W4236020781 hasRelatedWork W2999446179 @default.
- W4236020781 hasRelatedWork W74726072 @default.
- W4236020781 hasVolume "27" @default.
- W4236020781 isParatext "false" @default.
- W4236020781 isRetracted "false" @default.
- W4236020781 workType "article" @default.