Ulcerative colitis (UC) is difficult to treat and standard therapy does not always induce remissi... more Ulcerative colitis (UC) is difficult to treat and standard therapy does not always induce remission. Fecal microbial transplantation (FMT) is an alternative approach that induced remission in in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled, randomized trial. We performed a parallel study of patients with active UC without infectious diarrhea. Participants were examined by flexible sigmoidoscopy when the study began and then were randomly assigned to groups that received FMT (50 ml, via enema, from healthy anonymous donors; n=38) or placebo (50 ml water enema; n=37) once weekly for 6 weeks. Patients, clinicians, and investigators were blinded to the groups. The primary outcome was remission of UC, defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0, at week 7. Patients provided stool samples when the study began and during each week of FMT for microbiome analysis. The trial was stopped early for futility by the da...
Canadian journal of gastroenterology = Journal canadien de gastroenterologie, 2006
To determine the test characteristics and the optimal cut-off point for the (13)C urea breath tes... more To determine the test characteristics and the optimal cut-off point for the (13)C urea breath test ((13)C UBT) in a Canadian community laboratory setting. Of 2232 patients (mean age +/- SD: 51+/-21 years, 56% female) who completed a (13)C UBT, 1209 were tested to evaluate the primary diagnosis of (Helicobacter pylori) infection and 1023 were tested for confirmation of eradication following treatment. Cluster analysis was performed on the (13)C UBT data to determine the optimal cut-off point and the risk of false-positive and false-negative results. Additionally, 176 patients underwent endoscopic biopsy to allow validation of the sensitivity and specificity of the (13)C UBT against histology and microbiology using the calculated cut-off point. The calculated cut-off points were 3.09 delta/1000 for the whole study population (n=2232), 3.09 delta/1000 for the diagnosis group (n=1209) and 2.88 delta/1000 for the post-treatment group (n=1023). When replacing the calculated cut-off points...
Canadian journal of gastroenterology = Journal canadien de gastroenterologie, 2006
To determine whether a shortened (13)C urea breath test ((13)C UBT) (breath collection time of 10... more To determine whether a shortened (13)C urea breath test ((13)C UBT) (breath collection time of 10 min) is as reliable as the standard assay (30 min). Two hundred ninety-seven patients (mean +/- SD: 53+/-16 years, 57% female) completed a (13)C UBT. Breath samples were obtained at baseline and at 5 min intervals up to 30 min. Sixty-seven patients also underwent endoscopic biopsy. Cluster analysis was performed on the (13)C UBT data to determine the optimal cut-off point at each time interval. Sensitivity and specificity of the (13)C UBT at all intervals compared with histology and culture and against the standard 30 min interval were determined. The calculated optimal cut-off points for each time interval (T), expressed as delta over baseline (delta/1000), were 3.29 delta/1000 at T(5), 3.15 delta/1000 at T(10), 3.42 delta/1000 at T(15), 3.17 delta/1000 at T(20), 2.99 delta/1000 at T(25) and 2.82 delta/1000 at T(30). Except at T(5), the risk of false-positive and false-negative test re...
Background: Celiac disease (CeD) is a genetic autoimmune condition affecting 1% of the western po... more Background: Celiac disease (CeD) is a genetic autoimmune condition affecting 1% of the western population. Triggered by the ingestion of gluten, CeD is managed by a Gluten-Free diet (GFD), however recurrent symptoms due to inadvertent exposure and non-adherence to GFD are common and found in up to 71.8% of individuals with CeD. Symptoms can significantly impact quality of life and the disease is associated with an increased risk of gastrointestinal (GI) cancers and T-cell lymphoma. Tight junctions (TJ) control paracellular permeability, increased in CeD, caused in part, by an inflammatory immune response subsequent to paracellular transport of gluten peptides into the intestinal lamina propria through epithelial TJs. Larazotide acetate is a first-in-class oral peptide that prevents TJ opening and reduces gluten uptake, inhibiting gluten and cytokine-induced intestinal permeability and inflammation in vivo. The aim of the study was to investigate the efficacy of Larazotide acetate to improve signs and symptoms in individuals with CeD while on a GFD. Methods: In this outpatient, randomized, parallel, double-blind, placebo-controlled, multicenter study, conducted in 74 sites in North America, 342 CeD patients on a GFD for ≥12 months were randomized to receive placebo or Larazotide acetate 0.5, 1, or 2 mg three times daily (TID). The 20-week study had a 4-week placebo run-in, 12-week treatment phase, and 4-week placebo run-out. The primary outcome was the average on-treatment score in the Celiac Disease Gastrointestinal Symptom Rating Scale (CeD GSRS) domains of Diarrhea, Indigestion, and Abdominal pain. Results: The primary endpoint of symptom reduction was met at the 0.5 mg dose of Larazotide acetate compared with placebo in both Modified Intention To Treat (MITT) (ANCOVA p=0.022, MMRM p=0.005) and Per Protocol (PP) analysis (ANCOVA p=0.007, MMRM p=0.001) ). The 0.5 mg dose showed favorable outcomes for CeD Patient Reported Outcome (CeD PRO) GI domain, decrease in CeD PRO Symptomatic days (MITT ANCOVA 0.017) , an increase in Symptom-Free days (MITT ANCOVA p=0.034) and a decrease in Non-GI symptoms (MITT ANCOVA p=0.010). No increases in anti-tTG (IgA and IgG) titers were observed at any dose of Larazotide acetate. Safety of Larazotide acetate was comparable to placebo. Conclusion: Larazotide acetate 0.5 mg reduced GI and non-GI symptoms, while reducing the number of Symptomatic days. The safety and tolerability profile of Larazotide acetate was comparable to placebo. This study represents the first large therapeutic trial in CeD to meet its primary endpoint of reducing signs and symptoms and is the first successful trial of a novel class of agents targeting TJ regulation. Larazotide acetate 0.5 mg has the potential to be the first pharmacologic CeD treatment and warrants further investigation in Phase III clinical trials.
EGD-Colonoscopy sequence group (G-I) or Colonoscopy-EGD sequence group (G-II) by computer generat... more EGD-Colonoscopy sequence group (G-I) or Colonoscopy-EGD sequence group (G-II) by computer generated list. One endoscopist performed both EGD and colonoscopy of all patients. EGD was recorded on videotapes and the quality of EGD was assessed by three endoscopist all blinded to patient data by means of scoring about 18 assessment items that each represented a step of EGD (score 1: excellent -score 6: very poor). Colonoscopic insertion time to cecum, total time and prolonged insertion time (>10 minutes) were analyzed as well. In addition, the patients filled in questionnaires that asked subjective strenuous scale (0: not strenuous -100: worst), and preference for sequence of both EGD and colonoscopy. Results: Patients in the two groups (40:40) were well matched with respect to demo-
... W1029 Information Needs of Digestive Disease Patients: the Patient Education Needs Survey (PE... more ... W1029 Information Needs of Digestive Disease Patients: the Patient Education Needs Survey (PENS). Marroon Thabane ,; Usha Chauhan ,; Melanie A. Wolfe ,; Theresa Harper ,; NooriAkhtar-Danesh ,; Marko Simunovic ,; John K. Marshall ,; David Armstrong. PDF. ...
Ulcerative colitis (UC) is difficult to treat and standard therapy does not always induce remissi... more Ulcerative colitis (UC) is difficult to treat and standard therapy does not always induce remission. Fecal microbial transplantation (FMT) is an alternative approach that induced remission in in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled, randomized trial. We performed a parallel study of patients with active UC without infectious diarrhea. Participants were examined by flexible sigmoidoscopy when the study began and then were randomly assigned to groups that received FMT (50 ml, via enema, from healthy anonymous donors; n=38) or placebo (50 ml water enema; n=37) once weekly for 6 weeks. Patients, clinicians, and investigators were blinded to the groups. The primary outcome was remission of UC, defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0, at week 7. Patients provided stool samples when the study began and during each week of FMT for microbiome analysis. The trial was stopped early for futility by the da...
Canadian journal of gastroenterology = Journal canadien de gastroenterologie, 2006
To determine the test characteristics and the optimal cut-off point for the (13)C urea breath tes... more To determine the test characteristics and the optimal cut-off point for the (13)C urea breath test ((13)C UBT) in a Canadian community laboratory setting. Of 2232 patients (mean age +/- SD: 51+/-21 years, 56% female) who completed a (13)C UBT, 1209 were tested to evaluate the primary diagnosis of (Helicobacter pylori) infection and 1023 were tested for confirmation of eradication following treatment. Cluster analysis was performed on the (13)C UBT data to determine the optimal cut-off point and the risk of false-positive and false-negative results. Additionally, 176 patients underwent endoscopic biopsy to allow validation of the sensitivity and specificity of the (13)C UBT against histology and microbiology using the calculated cut-off point. The calculated cut-off points were 3.09 delta/1000 for the whole study population (n=2232), 3.09 delta/1000 for the diagnosis group (n=1209) and 2.88 delta/1000 for the post-treatment group (n=1023). When replacing the calculated cut-off points...
Canadian journal of gastroenterology = Journal canadien de gastroenterologie, 2006
To determine whether a shortened (13)C urea breath test ((13)C UBT) (breath collection time of 10... more To determine whether a shortened (13)C urea breath test ((13)C UBT) (breath collection time of 10 min) is as reliable as the standard assay (30 min). Two hundred ninety-seven patients (mean +/- SD: 53+/-16 years, 57% female) completed a (13)C UBT. Breath samples were obtained at baseline and at 5 min intervals up to 30 min. Sixty-seven patients also underwent endoscopic biopsy. Cluster analysis was performed on the (13)C UBT data to determine the optimal cut-off point at each time interval. Sensitivity and specificity of the (13)C UBT at all intervals compared with histology and culture and against the standard 30 min interval were determined. The calculated optimal cut-off points for each time interval (T), expressed as delta over baseline (delta/1000), were 3.29 delta/1000 at T(5), 3.15 delta/1000 at T(10), 3.42 delta/1000 at T(15), 3.17 delta/1000 at T(20), 2.99 delta/1000 at T(25) and 2.82 delta/1000 at T(30). Except at T(5), the risk of false-positive and false-negative test re...
Background: Celiac disease (CeD) is a genetic autoimmune condition affecting 1% of the western po... more Background: Celiac disease (CeD) is a genetic autoimmune condition affecting 1% of the western population. Triggered by the ingestion of gluten, CeD is managed by a Gluten-Free diet (GFD), however recurrent symptoms due to inadvertent exposure and non-adherence to GFD are common and found in up to 71.8% of individuals with CeD. Symptoms can significantly impact quality of life and the disease is associated with an increased risk of gastrointestinal (GI) cancers and T-cell lymphoma. Tight junctions (TJ) control paracellular permeability, increased in CeD, caused in part, by an inflammatory immune response subsequent to paracellular transport of gluten peptides into the intestinal lamina propria through epithelial TJs. Larazotide acetate is a first-in-class oral peptide that prevents TJ opening and reduces gluten uptake, inhibiting gluten and cytokine-induced intestinal permeability and inflammation in vivo. The aim of the study was to investigate the efficacy of Larazotide acetate to improve signs and symptoms in individuals with CeD while on a GFD. Methods: In this outpatient, randomized, parallel, double-blind, placebo-controlled, multicenter study, conducted in 74 sites in North America, 342 CeD patients on a GFD for ≥12 months were randomized to receive placebo or Larazotide acetate 0.5, 1, or 2 mg three times daily (TID). The 20-week study had a 4-week placebo run-in, 12-week treatment phase, and 4-week placebo run-out. The primary outcome was the average on-treatment score in the Celiac Disease Gastrointestinal Symptom Rating Scale (CeD GSRS) domains of Diarrhea, Indigestion, and Abdominal pain. Results: The primary endpoint of symptom reduction was met at the 0.5 mg dose of Larazotide acetate compared with placebo in both Modified Intention To Treat (MITT) (ANCOVA p=0.022, MMRM p=0.005) and Per Protocol (PP) analysis (ANCOVA p=0.007, MMRM p=0.001) ). The 0.5 mg dose showed favorable outcomes for CeD Patient Reported Outcome (CeD PRO) GI domain, decrease in CeD PRO Symptomatic days (MITT ANCOVA 0.017) , an increase in Symptom-Free days (MITT ANCOVA p=0.034) and a decrease in Non-GI symptoms (MITT ANCOVA p=0.010). No increases in anti-tTG (IgA and IgG) titers were observed at any dose of Larazotide acetate. Safety of Larazotide acetate was comparable to placebo. Conclusion: Larazotide acetate 0.5 mg reduced GI and non-GI symptoms, while reducing the number of Symptomatic days. The safety and tolerability profile of Larazotide acetate was comparable to placebo. This study represents the first large therapeutic trial in CeD to meet its primary endpoint of reducing signs and symptoms and is the first successful trial of a novel class of agents targeting TJ regulation. Larazotide acetate 0.5 mg has the potential to be the first pharmacologic CeD treatment and warrants further investigation in Phase III clinical trials.
EGD-Colonoscopy sequence group (G-I) or Colonoscopy-EGD sequence group (G-II) by computer generat... more EGD-Colonoscopy sequence group (G-I) or Colonoscopy-EGD sequence group (G-II) by computer generated list. One endoscopist performed both EGD and colonoscopy of all patients. EGD was recorded on videotapes and the quality of EGD was assessed by three endoscopist all blinded to patient data by means of scoring about 18 assessment items that each represented a step of EGD (score 1: excellent -score 6: very poor). Colonoscopic insertion time to cecum, total time and prolonged insertion time (>10 minutes) were analyzed as well. In addition, the patients filled in questionnaires that asked subjective strenuous scale (0: not strenuous -100: worst), and preference for sequence of both EGD and colonoscopy. Results: Patients in the two groups (40:40) were well matched with respect to demo-
... W1029 Information Needs of Digestive Disease Patients: the Patient Education Needs Survey (PE... more ... W1029 Information Needs of Digestive Disease Patients: the Patient Education Needs Survey (PENS). Marroon Thabane ,; Usha Chauhan ,; Melanie A. Wolfe ,; Theresa Harper ,; NooriAkhtar-Danesh ,; Marko Simunovic ,; John K. Marshall ,; David Armstrong. PDF. ...
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