Antimicrobial Therapy for Ulcerative Colitis (UC) (UC)

May 29, 2022 updated by: Prof. Arie Levine, Wolfson Medical Center

Antimicrobial Therapy for Ulcerative Colitis : Evaluation of Two Antibiotic Combinations for Refractory Ulcerative Colitis

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)

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Holon, Israel, 58100
        • The E.Wolfson Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group 1 -Amoxycillin Doxycyclin and metronidazole
triple therapy with amoxicillin, metronidazole and tetracycline twice daily, for 2 weeks.
Drug: 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
Other Names:
  • Amoxy, Flagyl, Doxylin
Experimental: Group 2 -Amoxycillin and Doxycyclin
double therapy with Amoxycillin and Doxycyclin twice daily, for 2 weeks.
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
Other Names:
  • Amoxy, Doxylin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy - Clinical Response in group 1 and 2 or Clinical Remission
Time Frame: Week 3

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.
Week 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy - Clinical Response in group 1 and 2
Time Frame: Week 6

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.
Week 6
EFFICACY - Remission
Time Frame: Week 6

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.
Week 6
EFFICACY - PGA
Time Frame: Week 6

Physicians Global Assessment

Values:

  1. Normal, not at all ill
  2. Borderline ill
  3. Mildly ill
  4. Moderately ill
  5. Markedly ill
  6. Severely ill
  7. Among the most extremely ill patients
Week 6
EFFICACY - Corticosteroid free remission
Time Frame: Week 6

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.
Week 6
EFFICACY - Corticosteroid free remission
Time Frame: Week 12

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.
Week 12
EFFICACY - Decrease in endoscopic disease activity
Time Frame: Week 12
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
Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wolfson Medical Center

Investigators

  • Principal Investigator: Dror Weiner, MD, Wolfson Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 25, 2019

Primary Completion (Actual)

May 29, 2022

Study Completion (Actual)

May 30, 2022

Study Registration Dates

First Submitted

June 4, 2019

First Submitted That Met QC Criteria

June 13, 2019

First Posted (Actual)

June 14, 2019

Study Record Updates

Last Update Posted (Actual)

June 1, 2022

Last Update Submitted That Met QC Criteria

May 29, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AntimicrobialUC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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