Antimicrobial Therapy for Ulcerative Colitis (UC)

Wolfson Medical Center (WMC)

Status and phase: Terminated; Phase 2

Conditions: Ulcerative Colitis

Treatments: Drug: amoxicillin, metronidazole and doxycycline; Drug: amoxicillin and doxycyclin

Study type: Interventional

Funder types: Other

Identifiers

NCT03986996

AntimicrobialUC

Details and patient eligibility

About

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)

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 13 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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20 participants in 2 patient groups

Group 1 -Amoxycillin Doxycyclin and metronidazole

Active Comparator group

Description:

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

Treatment:

Drug: amoxicillin, metronidazole and doxycycline

Group 2 -Amoxycillin and Doxycyclin

Experimental group

Description:

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

Treatment:

Drug: amoxicillin and doxycyclin