Antimicrobial Therapy for Ulcerative Colitis (UC)

NCT03986996 | Terminated Phase 2

• 1 other identifier: AntimicrobialUC
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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)

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 3

Secondary Outcomes (6)

• Efficacy - Clinical Response in group 1 and 2

  Week 6

• EFFICACY - Remission

  Week 6

• EFFICACY - PGA

  Week 6

• EFFICACY - Corticosteroid free remission

  Week 6

• EFFICACY - Corticosteroid free remission

  Week 12

Study Arms (2)

Group 1 -Amoxycillin Doxycyclin and metronidazole

ACTIVE COMPARATOR

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

Drug: amoxicillin, metronidazole and doxycycline

Group 2 -Amoxycillin and Doxycyclin

EXPERIMENTAL

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

Drug: amoxicillin and doxycyclin

Interventions

amoxicillin, metronidazole and doxycycline 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

Also known as: Amoxy, Flagyl, Doxylin

Group 1 -Amoxycillin Doxycyclin and metronidazole

amoxicillin and doxycyclin 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

Also known as: Amoxy, Doxylin

Group 2 -Amoxycillin and Doxycyclin

Eligibility Criteria

• Age: 13 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wolfson Medical Center: lead

Study Sites (1)

The E.Wolfson Medical Center

Holon, 58100, Israel

Location

Related Publications (16)

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  PMID: 22907164 BACKGROUND

• 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.

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• 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.

  PMID: 24336217 BACKGROUND

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  PMID: 25037189 BACKGROUND

• 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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• 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.

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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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MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Amoxicillin; Metronidazole; Doxycycline

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Dror Weiner, MD

  Wolfson Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The investigator will be blinded to the study group
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Pediatric Gastroenterology and Nutrition Unit

Model Details: 2 groups with 1:1 randomization

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 14, 2019
• Study Start: July 25, 2019
• Primary Completion: May 29, 2022
• Study Completion: May 30, 2022
• Last Updated: June 1, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)