Back to resultsAntimicrobial Therapy for Ulcerative Colitis (UC) (UC)
Primary Purpose
Ulcerative Colitis
Status
Terminated
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
amoxicillin, metronidazole and doxycycline
amoxicillin and doxycyclin
Sponsored by
About this trial
This is an interventional treatment trial for Ulcerative Colitis focused on measuring Ulcerative Colitis
Eligibility Criteria
Inclusion Criteria:
- Established diagnosis of UC, disease confined to the large intestine, involving the rectosigmoid for at least 3 months.
- Weight >30 kg
- Mild to Moderate active disease, SCCAI of ≥5 and ≤ 10, 10 ≤ PUCAI ≤4.
- Refractory to mesalamine 6 weeks, or steroids > 14 days, or immunomodulator 12 weeks or biologics at least 12 weeks therapy.
Exclusion Criteria:
- Start of a new biologic in the previous 12 weeks.
- Proctitis
- Evidence for Clostridium difficile infection.
- Any proven current infection such as CMV, positive stool culture or parasite.
- Current Extra intestinal manifestation of UC such as active arthritis or PSC.
- Immune deficiency (other than drug induced).
- Current use of a calcineurin inhibitor
- Pregnancy.
- Suspected toxic megacolon, guarding on palpation, or signs of peritoneal inflammation
- Patients with other IBD unrelated disease such as autoimmune disorders, renal failure, fever or current infection (UTI, strep throat, pneumonia, etc), prior or current neoplasia
- Fever >38
- Participation in another clinical interventional trial
- An active malignant disease or a prior malignancy during the previous 5 years (excluding skin BCC).
- Anticipation for antibiotic use within the study period (such as for elective surgery or dental treatment).
- Acute severe UC in the past 3 months.
- Presence of a pouch or pouchitis.
Sites / Locations
- The E.Wolfson Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Group 1 -Amoxycillin Doxycyclin and metronidazole
Group 2 -Amoxycillin and Doxycyclin
Arm Description
triple therapy with amoxicillin, metronidazole and tetracycline twice daily, for 2 weeks.
double therapy with Amoxycillin and Doxycyclin twice daily, for 2 weeks.
Outcomes
Primary Outcome Measures
Efficacy - Clinical Response in group 1 and 2 or Clinical Remission
Response defined as a 3 point drop in SCCAI / 20 point drop in PUCAI or drop in less than 3/20 point but entering clinical remission, defined as a SCCAI score<5 / PUCAI score<10.
Remission defined as SCCAI score<5 / PUCAI score<10.
SCCAI - simple clinical colitis activity index. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher.
PUCAI - pediatric Ulcerative colitis activity index. The calculated score ranges from 0 to 85, where active disease is a score of 10 or higher.
Secondary Outcome Measures
Efficacy - Clinical Response in group 1 and 2
Mean/median SCCAI / PUCAI
SCCAI - simple clinical colitis activity index. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher.
PUCAI - pediatric Ulcerative colitis activity index. The calculated score ranges from 0 to 85, where active disease is a score of 10 or higher.
EFFICACY - Remission
SCCAI score<5 / PUCAI score<10.
SCCAI - simple clinical colitis activity index. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher.
PUCAI - pediatric Ulcerative colitis activity index. The calculated score ranges from 0 to 85, where active disease is a score of 10 or higher.
EFFICACY - PGA
Physicians Global Assessment
Values:
Normal, not at all ill
Borderline ill
Mildly ill
Moderately ill
Markedly ill
Severely ill
Among the most extremely ill patients
EFFICACY - Corticosteroid free remission
Remission defined as SCCAI score<5 / PUCAI score<10.
SCCAI - simple clinical colitis activity index. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher.
PUCAI - pediatric Ulcerative colitis activity index. The calculated score ranges from 0 to 85, where active disease is a score of 10 or higher.
EFFICACY - Corticosteroid free remission
Remission defined as SCCAI score<5 / PUCAI score<10.
SCCAI - simple clinical colitis activity index. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher.
PUCAI - pediatric Ulcerative colitis activity index. The calculated score ranges from 0 to 85, where active disease is a score of 10 or higher.
EFFICACY - Decrease in endoscopic disease activity
Decrease in endoscopic disease activity mesured with the Simple Endoscopic Score for Crohn's Disease (SES-CD). The calculated score ranges from 0 to 60
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03986996
Brief Title
Antimicrobial Therapy for Ulcerative Colitis (UC)
Acronym
UC
Official Title
Antimicrobial Therapy for Ulcerative Colitis : Evaluation of Two Antibiotic Combinations for Refractory Ulcerative Colitis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
There is no feasibility to conduct the study
Study Start Date
July 25, 2019 (Actual)
Primary Completion Date
May 29, 2022 (Actual)
Study Completion Date
May 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Wolfson Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The Aim of this randoized controlled pilot study is to find a better treatment strategy for active UC based on the recent knowledge regarding the microbiota in UC and the beneficial or detrimental effects of antibiotics in restoring gut health and reducing inflammation. This study is designed to determine whether therapy with two antibiotics during a flare - amoxicillin and doxycillin, will be better than the current published antibiotic treatment combination using these antibiotics with metronidazole ( as the latter which may degrade beneficial species without adding benefit towards reducing pathobionts)
Detailed Description
Recent studies suggest that UC is associated with alterations of the microbiota. Further support for targeting the microbiota includes several studies demonstrating that antibiotics might be helpful for severe refractory colitis. Antibiotics may work by reducing pathobionts, by causing niche expansion of beneficial bacteria , and may harm if they do not reduce pathobionts or reduce beneficial commensals Recently, a triple antibiotic therapy with amoxicillin, metronidazole and tetracycline was developed for UC. However, a recent study on the effect of 11 different oral antibiotics on gut bacteria found that seven of them including metronidazole might cause lbacterial translocation . Anaerobes are critical for butyrate production. .
Based on these recent studies, it would appear that tetracycline and amoxicillin are more likely to cause the beneficial effect, while metronidazole might actually be detrimental. Thus by removing metronidazole the investigators might actually have a better effect both for efficacy and safety.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis
Keywords
Ulcerative Colitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
2 groups with 1:1 randomization
Masking
Investigator
Masking Description
The investigator will be blinded to the study group
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1 -Amoxycillin Doxycyclin and metronidazole
Arm Type
Active Comparator
Arm Description
triple therapy with amoxicillin, metronidazole and tetracycline twice daily, for 2 weeks.
Arm Title
Group 2 -Amoxycillin and Doxycyclin
Arm Type
Experimental
Arm Description
double therapy with Amoxycillin and Doxycyclin twice daily, for 2 weeks.
Intervention Type
Drug
Intervention Name(s)
amoxicillin, metronidazole and doxycycline
Other Intervention Name(s)
Amoxy, Flagyl, Doxylin
Intervention Description
antibiotics: Patient weight 30-50 kg Patient weight > 50 kg Tetracycline 50 mg X 2 Day X 2 weeks 100 mg X 2 Day X 2 weeks Amoxicillin 750 mg X 2 Day X 2 weeks 750 mg X 2 Day X 2 weeks Metronidazole 250 mg X 2 Day X 2 weeks 375 mg X 2 Day X 2 weeks
Intervention Type
Drug
Intervention Name(s)
amoxicillin and doxycyclin
Other Intervention Name(s)
Amoxy, Doxylin
Intervention Description
antibiotics: Patient weight 30-50 kg Patient weight > 50 kg Tetracycline 50 mg X 2 Day X 2 weeks 100 mg X 2 Day X 2 weeks Amoxicillin 750 mg X 2 Day X 2 weeks 750 mg X 2 Day X 2 weeks
Primary Outcome Measure Information:
Title
Efficacy - Clinical Response in group 1 and 2 or Clinical Remission
Description
Response defined as a 3 point drop in SCCAI / 20 point drop in PUCAI or drop in less than 3/20 point but entering clinical remission, defined as a SCCAI score<5 / PUCAI score<10.
Remission defined as SCCAI score<5 / PUCAI score<10.
SCCAI - simple clinical colitis activity index. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher.
PUCAI - pediatric Ulcerative colitis activity index. The calculated score ranges from 0 to 85, where active disease is a score of 10 or higher.
Time Frame
Week 3
Secondary Outcome Measure Information:
Title
Efficacy - Clinical Response in group 1 and 2
Description
Mean/median SCCAI / PUCAI
SCCAI - simple clinical colitis activity index. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher.
PUCAI - pediatric Ulcerative colitis activity index. The calculated score ranges from 0 to 85, where active disease is a score of 10 or higher.
Time Frame
Week 6
Title
EFFICACY - Remission
Description
SCCAI score<5 / PUCAI score<10.
SCCAI - simple clinical colitis activity index. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher.
PUCAI - pediatric Ulcerative colitis activity index. The calculated score ranges from 0 to 85, where active disease is a score of 10 or higher.
Time Frame
Week 6
Title
EFFICACY - PGA
Description
Physicians Global Assessment
Values:
Normal, not at all ill
Borderline ill
Mildly ill
Moderately ill
Markedly ill
Severely ill
Among the most extremely ill patients
Time Frame
Week 6
Title
EFFICACY - Corticosteroid free remission
Description
Remission defined as SCCAI score<5 / PUCAI score<10.
SCCAI - simple clinical colitis activity index. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher.
PUCAI - pediatric Ulcerative colitis activity index. The calculated score ranges from 0 to 85, where active disease is a score of 10 or higher.
Time Frame
Week 6
Title
EFFICACY - Corticosteroid free remission
Description
Remission defined as SCCAI score<5 / PUCAI score<10.
SCCAI - simple clinical colitis activity index. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher.
PUCAI - pediatric Ulcerative colitis activity index. The calculated score ranges from 0 to 85, where active disease is a score of 10 or higher.
Time Frame
Week 12
Title
EFFICACY - Decrease in endoscopic disease activity
Description
Decrease in endoscopic disease activity mesured with the Simple Endoscopic Score for Crohn's Disease (SES-CD). The calculated score ranges from 0 to 60
Time Frame
Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Established diagnosis of UC, disease confined to the large intestine, involving the rectosigmoid for at least 3 months.
Weight >30 kg
Mild to Moderate active disease, SCCAI of ≥5 and ≤ 10, 10 ≤ PUCAI ≤4.
Refractory to mesalamine 6 weeks, or steroids > 14 days, or immunomodulator 12 weeks or biologics at least 12 weeks therapy.
Exclusion Criteria:
Start of a new biologic in the previous 12 weeks.
Proctitis
Evidence for Clostridium difficile infection.
Any proven current infection such as CMV, positive stool culture or parasite.
Current Extra intestinal manifestation of UC such as active arthritis or PSC.
Immune deficiency (other than drug induced).
Current use of a calcineurin inhibitor
Pregnancy.
Suspected toxic megacolon, guarding on palpation, or signs of peritoneal inflammation
Patients with other IBD unrelated disease such as autoimmune disorders, renal failure, fever or current infection (UTI, strep throat, pneumonia, etc), prior or current neoplasia
Fever >38
Participation in another clinical interventional trial
An active malignant disease or a prior malignancy during the previous 5 years (excluding skin BCC).
Anticipation for antibiotic use within the study period (such as for elective surgery or dental treatment).
Acute severe UC in the past 3 months.
Presence of a pouch or pouchitis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dror Weiner, MD
Organizational Affiliation
Wolfson Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
The E.Wolfson Medical Center
City
Holon
ZIP/Postal Code
58100
Country
Israel
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23128233
Citation
Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Buning C, Cohain A, Cichon S, D'Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H; International IBD Genetics Consortium (IIBDGC); Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature. 2012 Nov 1;491(7422):119-24. doi: 10.1038/nature11582.
Results Reference
background
PubMed Identifier
22907164
Citation
Manichanh C, Borruel N, Casellas F, Guarner F. The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol. 2012 Oct;9(10):599-608. doi: 10.1038/nrgastro.2012.152. Epub 2012 Aug 21.
Results Reference
background
PubMed Identifier
21073731
Citation
Noor SO, Ridgway K, Scovell L, Kemsley EK, Lund EK, Jamieson C, Johnson IT, Narbad A. Ulcerative colitis and irritable bowel patients exhibit distinct abnormalities of the gut microbiota. BMC Gastroenterol. 2010 Nov 12;10:134. doi: 10.1186/1471-230X-10-134.
Results Reference
background
PubMed Identifier
24583479
Citation
Davenport M, Poles J, Leung JM, Wolff MJ, Abidi WM, Ullman T, Mayer L, Cho I, Loke P. Metabolic alterations to the mucosal microbiota in inflammatory bowel disease. Inflamm Bowel Dis. 2014 Apr;20(4):723-31. doi: 10.1097/MIB.0000000000000011.
Results Reference
background
PubMed Identifier
24336217
Citation
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11.
Results Reference
background
PubMed Identifier
25037189
Citation
James SL, Christophersen CT, Bird AR, Conlon MA, Rosella O, Gibson PR, Muir JG. Abnormal fibre usage in UC in remission. Gut. 2015 Apr;64(4):562-70. doi: 10.1136/gutjnl-2014-307198. Epub 2014 Jul 18.
Results Reference
background
PubMed Identifier
23941288
Citation
Khalil NA, Walton GE, Gibson GR, Tuohy KM, Andrews SC. In vitro batch cultures of gut microbiota from healthy and ulcerative colitis (UC) subjects suggest that sulphate-reducing bacteria levels are raised in UC and by a protein-rich diet. Int J Food Sci Nutr. 2014 Feb;65(1):79-88. doi: 10.3109/09637486.2013.825700. Epub 2013 Aug 13.
Results Reference
background
PubMed Identifier
22434643
Citation
De Preter V, Arijs I, Windey K, Vanhove W, Vermeire S, Schuit F, Rutgeerts P, Verbeke K. Decreased mucosal sulfide detoxification is related to an impaired butyrate oxidation in ulcerative colitis. Inflamm Bowel Dis. 2012 Dec;18(12):2371-80. doi: 10.1002/ibd.22949. Epub 2012 Mar 20.
Results Reference
background
PubMed Identifier
15361498
Citation
Jowett SL, Seal CJ, Pearce MS, Phillips E, Gregory W, Barton JR, Welfare MR. Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study. Gut. 2004 Oct;53(10):1479-84. doi: 10.1136/gut.2003.024828.
Results Reference
background
PubMed Identifier
10601057
Citation
Pitcher MC, Beatty ER, Cummings JH. The contribution of sulphate reducing bacteria and 5-aminosalicylic acid to faecal sulphide in patients with ulcerative colitis. Gut. 2000 Jan;46(1):64-72. doi: 10.1136/gut.46.1.64.
Results Reference
background
PubMed Identifier
16334443
Citation
Ohkusa T, Nomura T, Terai T, Miwa H, Kobayashi O, Hojo M, Takei Y, Ogihara T, Hirai S, Okayasu I, Sato N. Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up. Scand J Gastroenterol. 2005 Nov;40(11):1334-42. doi: 10.1080/00365520510023648.
Results Reference
background
PubMed Identifier
20216533
Citation
Ohkusa T, Kato K, Terao S, Chiba T, Mabe K, Murakami K, Mizokami Y, Sugiyama T, Yanaka A, Takeuchi Y, Yamato S, Yokoyama T, Okayasu I, Watanabe S, Tajiri H, Sato N; Japan UC Antibiotic Therapy Study Group. Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial. Am J Gastroenterol. 2010 Aug;105(8):1820-9. doi: 10.1038/ajg.2010.84. Epub 2010 Mar 9.
Results Reference
background
PubMed Identifier
24958064
Citation
Turner D, Levine A, Kolho KL, Shaoul R, Ledder O. Combination of oral antibiotics may be effective in severe pediatric ulcerative colitis: a preliminary report. J Crohns Colitis. 2014 Nov;8(11):1464-70. doi: 10.1016/j.crohns.2014.05.010. Epub 2014 Jun 20.
Results Reference
background
PubMed Identifier
21266816
Citation
Terao S, Yamashiro K, Tamura I, Hirano T, Ohkusa T, Kato K. Antibiotic combination therapy for steroid withdrawal in steroid-dependent ulcerative colitis. Digestion. 2011;83(3):198-203. doi: 10.1159/000321811. Epub 2011 Jan 21.
Results Reference
background
PubMed Identifier
24628398
Citation
Kato K, Ohkusa T, Terao S, Chiba T, Murakami K, Yanaka A, Uehara T, Ishii Y, Soma M, Tajiri H. Adjunct antibiotic combination therapy for steroid-refractory or -dependent ulcerative colitis: an open-label multicentre study. Aliment Pharmacol Ther. 2014 May;39(9):949-56. doi: 10.1111/apt.12688. Epub 2014 Mar 13.
Results Reference
background
PubMed Identifier
26045138
Citation
Knoop KA, McDonald KG, Kulkarni DH, Newberry RD. Antibiotics promote inflammation through the translocation of native commensal colonic bacteria. Gut. 2016 Jul;65(7):1100-9. doi: 10.1136/gutjnl-2014-309059. Epub 2015 Jun 4.
Results Reference
background
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Antimicrobial Therapy for Ulcerative Colitis (UC)
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