EVALUATION OF A DIET AND ANTIBIOTICS TARGETING THE MICROBIOTA FOR TREATMENT OF MILD TO MODETARE ACTIVE PEDIARTIC ULCERATIVE COLITIS: AN OPEN LABEL PILOT STUDY

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S38-S38
Author(s):  
Chen Sarbagili-Shabat ◽  
Lindsey Albenberg ◽  
Johan Van Limbergen ◽  
Dror Weiner ◽  
Michal Yaakov ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Pilot Study ◽  
Dietary Intervention ◽  
Activity Index ◽  
Fecal Calprotectin ◽  
Dietary Therapy ◽  
The Novel ◽  
Open Label ◽  
Intention To Treat ◽  
Stable Maintenance

Abstract Background Newer strategies that target the microbiome may offer an alternative therapeutic approach for Ulcerative Colitis (UC). We developed a novel diet that targets changes in the microbiome and barrier function that have been reported in UC. The goal of the current study was to evaluate the efficacy of two sequential induction of remission strategies that target the microbiota: the novel diet termed the ulcerative colitis diet (UCD) and an antibiotics cocktail combination in dietary non responders. Methods This was a prospective, single arm, open label, pilot study in patients aged 8–19, with a pediatric UC activity index (PUCAI) scores >10 and ≤45 on stable maintenance therapy (5ASA or thiopurines). PUCAI score was assessed at week 3 and 6. Patients failing to enter remission or intolerant to dietary therapy could receive an open label 14-day course of Amoxycillin, Metronidazole and Doxycycline (AMD), and had PUCAI scored at day 21. Response was defined a decline in PUCAI ≥ 10 points, remission as PUCAI< 10. The primary endpoint was intention to treat (ITT) remission at week 6 with diet as the sole intervention. Results Twenty-three children mean age of 15.1±2.9 years were enrolled. Two patients (1 responder, 1 remission) withdrew by 3 weeks, four required additional therapy by week 3, all were considered failures by ITT. Mean PUCAI decreased at week 3 and 6 from 34.5±9.8 to 21.7±14.9 and 17.6±17.2 respectively (P=0.005, P=0.001) at ITT analysis including all patients. Sixteen out of twenty-three patients (69.6%) responded by week 6. Ten of twenty-three (43.5%) achieved remission by week 6, and nine (39.1%) had clinical remission at week 6. The median fecal calprotectin (FC) level decreased in patients (n=5) who achieved remission from 630 (IQR, 332–1586) μg/g at week 0 to 230 (75–1298) μg/g at week 6. Eight patients received treatment with antibiotics after failing diet, 4/8 (50.0%) subsequently entered remission. Conclusion A dietary intervention called the UC Diet appears to be effective for induction of remission in children with mild to moderate UC. Sequential use of diet, followed by antibiotic therapy in dietary non responders, needs further evaluation as a microbiome directed steroid sparing therapy in patient’s refractory to 5ASA and thiopurines.

scholarly journals A Novel UC Exclusion Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A Prospective Open-Label Pilot Study

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3736
Author(s):  
Chen Sarbagili-Shabat ◽  
Lindsey Albenberg ◽  
Johan Van Limbergen ◽  
Naomi Pressman ◽  
Anthony Otley ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Pilot Study ◽  
Clinical Remission ◽  
Activity Index ◽  
Pilot Trial ◽  
Fecal Calprotectin ◽  
Open Label ◽  
Intention To Treat ◽  
Exclusion Diet ◽  
Stable Maintenance

Background: As the microbiome plays an important role in instigating inflammation in ulcerative colitis (UC), strategies targeting the microbiome may offer an alternative therapeutic approach. The goal of the pilot trial was to evaluate the potential efficacy and feasibility of a novel UC exclusion diet (UCED) for clinical remission, as well as the potential of sequential antibiotics for diet-refractory patients to achieve remission without steroids. Methods: This was a prospective, single-arm, multicenter, open-label pilot study in patients aged 8–19, with pediatric UC activity index (PUCAI) scores >10 on stable maintenance therapy. Patients failing to enter remission (PUCAI < 10) on the diet could receive a 14-day course of amoxycillin, metronidazole and doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention-to-treat (ITT) remission at week 6, with UCED as the only intervention. Results: Twenty-four UCED treatment courses were given to 23 eligible children (mean age: 15.3 ± 2.9 years). The median PUCAI decreased from 35 (30–40) at baseline to 12.5 (5–30) at week 6 (p = 0.001). Clinical remission with UCED alone was achieved in 9/24 (37.5%). The median fecal calprotectin declined from 818 (630.0–1880.0) μg/g at baseline to 592.0 (140.7–1555.0) μg/g at week 6 (p > 0.05). Eight patients received treatment with antibiotics after failing on the diet; 4/8 (50.0%) subsequently entered remission 3 weeks later. Conclusion: The UCED appears to be effective and feasible for the induction of remission in children with mild to moderate UC. The sequential use of UCED followed by antibiotic therapy needs to be evaluated as a microbiome-targeted, steroid-sparing strategy.

scholarly journals P492 The UC Diet and Antibiotics for Treatment of Mild to Moderate Pediatric Ulcerative Colitis: A prospective open label pilot study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S476-S477
Author(s):  
C Sarbagili Shabat ◽  
L Albenberg ◽  
J Van Limbergen ◽  
A Otley ◽  
M Yaakov ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Pilot Study ◽  
Clinical Remission ◽  
Activity Index ◽  
Pilot Trial ◽  
Open Label ◽  
Intention To Treat ◽  
Alternative Therapeutic Approach ◽  
Stable Maintenance ◽  
Steroid Sparing

Abstract Background Strategies that target the microbiome may offer an alternative therapeutic approach for Ulcerative Colitis (UC). The goal of the pilot trial was to evaluate the efficacy of a novel microbe-directed UC diet (UCD) for clinical remission, as well as use of antibiotics for dietary refractory patients as an alternative strategy for remission. Methods This was a prospective, single arm, open label, pilot study in patients aged 8–19, with a pediatric UC activity index (PUCAI) scores &gt;10 on stable maintenance therapy. Patients failing to enter remission (PUCAI&lt;10) on diet could receive a 14-day course of Amoxycillin, Metronidazole and Doxycycline (AMD), and were re-assessed on day 21. The primary endpoint was intention to treat (ITT) remission at week 6 with UCD. Results Twenty-four UCD treatment courses were given to 23 eligible children (mean age 15.3±2.9 years). Median PUCAI decreased from baseline 35 (30–40) to 12.5 (5–27.5) week 6 (P=0.001). Clinical remission with UCD alone was achieved in 9/24 (37.5%). Median calprotectin declined from baseline 818 (630.0–1880.0) to 592.0 (140.7–902.4) week 6. Eight patients received treatment with antibiotics after failing diet, 4/8 (50.0%) subsequently entered remission 3 weeks later. Conclusion The UC Diet appears to be effective for induction of remission in children with mild to moderate UC suggesting that diet could play a role in the disease. Sequential use of UCD followed by antibiotic therapy needs to be evaluated as a microbiome targeted steroid sparing strategy.

Multidonor FMT capsules improve symptoms and decrease fecal calprotectin in ulcerative colitis patients while treated – an open-label pilot study

2019 ◽  
Vol 54 (3) ◽  
pp. 289-296 ◽  
Author(s):  
F. Cold ◽  
P. D. Browne ◽  
S. Günther ◽  
S. I. Halkjaer ◽  
A. M. Petersen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Pilot Study ◽  
Fecal Calprotectin ◽  
Open Label

scholarly journals Efficacy of 5-Aminosalicylic Acid Enemas in the Treatment of Distal Ulcerative Colitis

1990 ◽  
Vol 4 (7) ◽  
pp. 468-471 ◽  
Author(s):  
MG Robinson ◽  
DL Decktor
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
First Episode ◽  
High Dose ◽  
Aminosalicylic Acid ◽  
Open Label ◽  
Distal Ulcerative Colitis ◽  
The Mean

The efficacy of 4 g 5-aminosalicylic acid (5-ASA, mesalamine) enemas was assessed in 666 patients with distal ulcerative colitis. Patients were enrolled in an open-label compassionate use program. One 4 g 5-ASA enema was administered each night for a period of four weeks and the disease activity index was assessed at baseline and on days 14 and 28. On days 14 and 28, 78.0% and 88.1% of patients, respectively, demonstrated an improvement in disease activity index. The mean decline in disease activity index on day 14 was 40.7% (P=0.0001) and on day 28 it was 55.4% (P=0.0001). Efficacy was similar whether the disease was confined to or extended beyond 30 cm from the anus. There was no difference in efficacy in patients suffering their first episode of disease compared to patients suffering subsequent attacks. In conclusion, high dose 5-ASA enemas are a highly effective treatment for distal ulcerative colitis.

scholarly journals Prebiotic Galactooligosaccharide Supplementation in Adults with Ulcerative Colitis: Exploring the Impact on Peripheral Blood Gene Expression, Gut Microbiota, and Clinical Symptoms

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3598
Author(s):  
Bridgette Wilson ◽  
Özge Eyice ◽  
Ioannis Koumoutsos ◽  
Miranda C. Lomer ◽  
Peter M. Irving ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Rating Scale ◽  
Activity Index ◽  
Fecal Calprotectin ◽  
Controlled Study ◽  
Gas Liquid Chromatography ◽  
Clinical Scores ◽  
Gastrointestinal Symptom Rating Scale ◽  
The Impact

Prebiotics may promote immune homeostasis and reduce sub-clinical inflammation in humans. This study investigated the effect of prebiotic galactooligosaccharide (GOS) supplementation in colonic inflammation. Seventeen patients with active ulcerative colitis (UC) consumed 2.8 g/d GOS for 6 weeks. At baseline and 6 weeks, gene expression (microarray), fecal calprotectin (ELISA), microbiota (16S rRNA), short-chain fatty acids (SCFAs; gas-liquid chromatography), and clinical outcomes (simple clinical colitis activity index (SCCAI), gastrointestinal symptom rating scale (GSRS), and Bristol stool form scale (BSFS)) were measured. Following prebiotics, clinical scores (SCCAI), fecal calprotectin, SCFAs, and pH were unchanged. Five genes were upregulated and two downregulated. Normal stool proportion (BSFS) increased (49% vs. 70%, p = 0.024), and the incidence (46% vs. 23%, p = 0.016) and severity (0.7 vs. 0.5, p = 0.048) of loose stool (GSRS), along with urgency (SCCAI) scores (1.0 vs. 0.5, p = 0.011), were reduced. In patients with a baseline SCCAI ≤2, prebiotics increased the relative abundance of Bifidobacterium from 1.65% (1.97) to 3.99% (5.37) (p = 0.046) and Christensenellaceae from 0.13% (0.33) to 0.31% (0.76) (p = 0.043). Prebiotics did not lower clinical scores or inflammation but normalized stools. Bifidobacterium and Christensenellaceae proportions only increased in patients with less active diseases, indicating that the prebiotic effect may depend on disease activity. A controlled study is required to validate these observations.

Novel Leucocyte/Thrombocyte Apheresis for Induction of Steroid-Free Remission in Ulcerative Colitis: A Controlled Randomized Pilot Study

2019 ◽  
Vol 13 (7) ◽  
pp. 949-953 ◽  
Author(s):  
Wolfgang Kruis ◽  
Phuong Nguyen ◽  
Julia Morgenstern ◽  
Wolfgang Ramlow ◽  
Axel Dignaß ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Pilot Study ◽  
Clinical Remission ◽  
Activity Index ◽  
Disease Activity Index ◽  
Oral Prednisolone ◽  
Serious Adverse Events ◽  
Symptomatic Infection ◽  
Reactive Protein ◽  
Group A

Abstract Background and Aims In active ulcerative colitis [UC] refractory to mesalazine, escalation to either steroids or immunosuppression is common practice. The efficacy and safety of alternative escalation therapy with a novel leukocyte apheresis device were studied. Methods This was a prospective, randomized, controlled multicentre pilot study comparing leukocyte apheresis with prednisolone in refractory UC (disease activity index [DAI] ≥ 4 and ≤8). Group A received weekly apheresis over five consecutive weeks. Group P received oral prednisolone 40 mg/day tapered to 0 mg at week 6. The primary end point was steroid-free clinical remission [DAI ≤ 2] at week 12. Clinical response was also analysed. Results Twenty-four patients were enrolled, 13 of whom were randomized into group A and 11 into group P. Clinical remission off steroids at week 12 was achieved in 3/12 patients [25.0%] with apheresis and 2/10 [20.0%] with prednisolone [p = 1.0]. The response rate after 12 weeks was 75.0% in group A and 50.0% in group P. Mean DAI scores improved in both treatment groups [p = 0.008]. C-reactive protein decreased from 6.0 ± 5.3 to 3.8 ± 3.7 mg/L at 12 weeks in group A and increased from 5.2 ± 6.0 to 6.3 ± 7.9 mg/mL in group P. Both treatments were well tolerated. No unexpected serious adverse events were seen in group A. In group P one symptomatic infection with Clostridium difficile occurred. Conclusions In patients with active UC refractory to mesalazine a novel leukocyte apheresis showed promising results. A comparison with prednisolone revealed similar therapeutic effectivity and excellent safety, providing the chance to escalate without systemic steroids.

Su1928 EVALUATING ASSOCIATION BETWEEN FECAL CALPROTECTIN AND ENDOSCOPIC OUTCOMES IN ULCERATIVE COLITIS USING THE HICKORY OPEN-LABEL INDUCTION COHORT

2020 ◽  
Vol 158 (6) ◽  
pp. S-706
Author(s):  
Walter Reinisch ◽  
Bouchra El Azzouzi ◽  
Regan Li ◽  
Stuart Lacey ◽  
Marco Daperno ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Calprotectin ◽  
Open Label

scholarly journals P416 Results of the first paediatric randomised controlled trial of faecal microbiota transplant for ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S379-S380
Author(s):  
N Pai ◽  
J Popov ◽  
L Hill ◽  
E Hartung ◽  
K Grzywacz ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Healthy Donor ◽  
Activity Index ◽  
Case Reports ◽  
Case Series ◽  
Faecal Microbiota ◽  
Open Label ◽  
Randomised Controlled

Abstract Background The role of faecal microbiota transplant (FMT) for the treatment of ulcerative colitis (UC) has been reported across 4 randomised-controlled trials (RCT) in adults. Promising data have emerged from small, open-label paediatric case series and case reports but a proper blinded, placebo-controlled RCT has not been described in children. We report results from the first multicentre RCT of FMT in paediatric UC patients, conducted over 36 months in Ontario and Quebec, Canada. Methods We enrolled 25 children, ages 4–17 years old with active UC across two tertiary IBD clinics. Patients had active inflammation and remained on stable doses of medication at entry. Blinded participants received enemas containing healthy donor stool (active) or normal saline (placebo), 2×/week for 6 weeks. Faecal calprotectin (fCal), C-reactive protein (CRP), and paediatric ulcerative colitis activity index (PUCAI) scores were compared between groups during intervention, and at four follow-up time points over 30 weeks. Donor and recipient stools were measured for 16s rRNA and metagenomics analyses. Results In intention-to-treat (ITT) analysis, FMT (n = 13) at 6 weeks was more likely to improve clinical response (OR 9.3, 95% CI [0.7, 122.6]), CRP (OR 4.7, 95% CI [0.8, 28.4]), and fCal (OR 13.3, 95% CI [1.1, 166.4]) from baseline compared with placebo (n = 12). FMT at 30 weeks was also more likely than placebo to improve clinical response, CRP, and fCal (Table 1). In ITT analysis of the open-label arm (n = 7), FMT at 6 weeks and 30 weeks decreased CRP (−42.9%, −28.6%), fCal (−28.6%, −42.9%), and PUCAI score (−14.3%, −42.9%) from baseline. Conclusion Serial FMT enemas containing healthy donor microbiota led to greater improvements in serum and stool inflammatory markers, and rates of clinical response, in paediatric patients with active UC compared with placebo. These improvements largely persisted beyond 6 months after final FMT treatment. This study offers the strongest preliminary evidence, from a blinded, placebo-controlled multicentre RCT for the role of FMT in the management of paediatric UC.

scholarly journals A Phase 2a, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of IBD98-M Delayed-Release Capsules to Induce Remission in Patients with Active and Mild to Moderate Ulcerative Colitis

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 523 ◽  
Author(s):  
Gionata Fiorino ◽  
Giacomo Carlo Sturniolo ◽  
Fabrizio Bossa ◽  
Andrea Cassinotti ◽  
Antonio Di Sabatino ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Activity Index ◽  
Controlled Trial ◽  
Disease Activity Index ◽  
Fecal Calprotectin ◽  
Summary Score ◽  
Double Blind ◽  
Release Formulation ◽  
Delayed Release

IBD98-M is a delayed-release formulation of mesalamine (mesalazine) and SH with a potential therapeutic role in ulcerative colitis (UC). A total of 51 patients with a modified Ulcerative Colitis Disease Activity Index (UCDAI) score of ≥4 and ≤10, and a modified UCDAI endoscopy subscore ≥1 were randomized for 6 weeks of double-blind treatment with IBD98 0.8 g/day or IBD 1.2 g/day or placebo. The efficacy and safety of IBD98-M in mild to moderate active UC were primarily evaluated. At week 6, 1 (5.9%), 2 (12.5%), and 2 (11.1%) patients receiving IBD98-M 0.8 g, IBD98-M 1.2 g, and placebo, respectively, (p > 0.999) achieved clinical remission. Higher clinical response was seen in IBD98-M 1.2 g (31.3%) versus placebo (16.7%) and endoscopic improvement in IBD98-M 0.8 g (29.4%) versus placebo (22.2%) was seen. Fecal calprotectin levels were reduced in IBD98-M groups versus placebo (p > 0.05). IBD98-M patients achieved significant improvement in physical health summary score component of the SF-36 (p = 0.01 and p = 0.03 respectively) compared to placebo. IBD98-M did not meet the primary end point but had higher clinical response (1.2 g/day) and endoscopic improvement (0.8 g/day) compared to placebo. The safety result shown that IBD98-M treatment was safe and well tolerated in this patient population. No new safety signals or unexpected safety findings were observed during the study. Further trials with different stratification and longer follow-up may be needed to evaluate the efficacy.

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