Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Antimicrobial Therapy for Ulcerative Colitis (UC) (UC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03986996
Recruitment Status : Recruiting
First Posted : June 14, 2019
Last Update Posted : April 23, 2021
Sponsor:
Information provided by (Responsible Party):
Prof. Arie Levine, Wolfson Medical Center

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)

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: amoxicillin, metronidazole and doxycycline Drug: amoxicillin and doxycyclin Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 2 groups with 1:1 randomization
Masking: Single (Investigator)
Masking Description: The investigator will be blinded to the study group
Primary Purpose: Treatment
Official Title: Antimicrobial Therapy for Ulcerative Colitis : Evaluation of Two Antibiotic Combinations for Refractory Ulcerative Colitis
Actual Study Start Date : July 25, 2019
Estimated Primary Completion Date : July 30, 2021
Estimated Study Completion Date : July 30, 2022


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 Name: 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 Name: Amoxy, Doxylin




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.


  2. 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.


  3. 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

  4. 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.


  5. 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.


  6. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   13 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03986996


Contacts
Layout table for location contacts
Contact: Michal Yaakov, Ph.D 972-3-5028878 MICHALY@wmc.gov.il

Locations
Layout table for location information
Israel
The E.Wolfson Medical Center Recruiting
Holon, Israel, 58100
Contact: Arie Levine, MD    +972-3-5028878    alevine@wolfson.health.gov.il   
Contact: Michal yaakov, PHD    972-35028878    MICHALY@WMC.GOV.IL   
Principal Investigator: Arie Levine, MD         
Sponsors and Collaborators
Wolfson Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Dror Weiner, MD Wolfson Medical Center
Publications:
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, Büning 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.

Layout table for additonal information
Responsible Party: Prof. Arie Levine, Director, Pediatric Gastroenterology and Nutrition Unit, Wolfson Medical Center
ClinicalTrials.gov Identifier: NCT03986996    
Other Study ID Numbers: AntimicrobialUC
First Posted: June 14, 2019    Key Record Dates
Last Update Posted: April 23, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Keywords provided by Prof. Arie Levine, Wolfson Medical Center:
Ulcerative Colitis
Additional relevant MeSH terms:
Layout table for MeSH terms
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Amoxicillin
Metronidazole
Doxycycline
Anti-Bacterial Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Antimalarials