Antimicrobial Therapy for Ulcerative Colitis (UC)

NCT ID: NCT03986996

Last Updated: 2022-06-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-25

Study Completion Date

2022-05-30

Brief Summary

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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

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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.

Conditions

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Ulcerative Colitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

2 groups with 1:1 randomization
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators
The investigator will be blinded to the study group

Study Groups

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Group 1 -Amoxycillin Doxycyclin and metronidazole

triple therapy with amoxicillin, metronidazole and tetracycline twice daily, for 2 weeks.

Group Type ACTIVE_COMPARATOR

amoxicillin, metronidazole and doxycycline

Intervention Type DRUG

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

Group 2 -Amoxycillin and Doxycyclin

double therapy with Amoxycillin and Doxycyclin twice daily, for 2 weeks.

Group Type EXPERIMENTAL

amoxicillin and doxycyclin

Intervention Type DRUG

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

Interventions

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amoxicillin, metronidazole and doxycycline

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

amoxicillin and doxycyclin

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

Intervention Type DRUG

Other Intervention Names

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Amoxy, Flagyl, Doxylin Amoxy, Doxylin

Eligibility Criteria

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Inclusion Criteria

1. Established diagnosis of UC, disease confined to the large intestine, involving the rectosigmoid for at least 3 months.
2. Weight \>30 kg
3. Mild to Moderate active disease, SCCAI of ≥5 and ≤ 10, 10 ≤ PUCAI ≤4.
4. Refractory to mesalamine 6 weeks, or steroids \> 14 days, or immunomodulator 12 weeks or biologics at least 12 weeks therapy.

Exclusion Criteria

1. Start of a new biologic in the previous 12 weeks.
2. Proctitis
3. Evidence for Clostridium difficile infection.
4. Any proven current infection such as CMV, positive stool culture or parasite.
5. Current Extra intestinal manifestation of UC such as active arthritis or PSC.
6. Immune deficiency (other than drug induced).
7. Current use of a calcineurin inhibitor
8. Pregnancy.
9. Suspected toxic megacolon, guarding on palpation, or signs of peritoneal inflammation
10. 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
11. Fever \>38
12. Participation in another clinical interventional trial
13. An active malignant disease or a prior malignancy during the previous 5 years (excluding skin BCC).
14. Anticipation for antibiotic use within the study period (such as for elective surgery or dental treatment).
15. Acute severe UC in the past 3 months.
16. Presence of a pouch or pouchitis.
Minimum Eligible Age

13 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Wolfson Medical Center

OTHER_GOV

Sponsor Role lead

Responsible Party

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Prof. Arie Levine

Director, Pediatric Gastroenterology and Nutrition Unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dror Weiner, MD

Role: PRINCIPAL_INVESTIGATOR

Wolfson Medical Center

Locations

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The E.Wolfson Medical Center

Holon, , Israel

Site Status

Countries

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Israel

References

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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.

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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.

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Reference Type BACKGROUND
PMID: 22434643 (View on PubMed)

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.

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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.

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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.

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Other Identifiers

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AntimicrobialUC

Identifier Type: -

Identifier Source: org_study_id

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