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Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease (Holiday)

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ClinicalTrials.gov Identifier: NCT03476317
Recruitment Status : Recruiting
First Posted : March 26, 2018
Last Update Posted : September 14, 2018
Sponsor:
Collaborators:
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Brief Summary:
The purpose of this study is to determine the effect of a novel gut microbiota-targeted therapeutic regimen (bowel lavage and antibiotics with or without an antifungal) in the management of active Crohn's Disease (CD) that is refractory to conventional, immunosuppressive therapy.

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Vancomycin Drug: Neomycin Drug: Ciprofloxacin Drug: Polyethylene Glycol 3350 Drug: Fluconazole Phase 2

Detailed Description:
Investigators will evaluate the efficacy of a novel treatment regimen, employing non-immunosuppressive medications, in the management of refractory CD. Refractory patients include those patients who have experienced loss of responsiveness (LOR) or primary nonresponse to an immunomodulator or a biologic. Investigators will treat participants with a combination of gut microbiota-targeted therapies to restore a healthy gut microbiome composition. Investigators believe that this strategy will both treat the gut inflammation associated with inflammatory bowel disease (IBD) as well as salvage response to immune suppressive therapies.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Open-Label Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
Actual Study Start Date : July 12, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease
Drug Information available for: Fluconazole

Arm Intervention/treatment
Experimental: Fluconazole
Vancomycin oral suspension four times daily (Day 1-14), plus neomycin orally three times daily (Days 1-3), plus ciprofloxacin orally twice daily (Day 4-14), plus Polyethylene Glycol 3350 (Miralax) dissolved in Gatorade on day 2, plus fluconazole orally once daily (Day 1-14).
Drug: Vancomycin
Oral suspension 4 times daily (Day 1-14)
Other Name: Vancocin

Drug: Neomycin
Oral three times daily (Days 1-3)
Other Name: Neo-Fradin

Drug: Ciprofloxacin
Oral twice daily (Days 4-14)
Other Name: Cipro

Drug: Polyethylene Glycol 3350
Dissolved in Gatorade on day 2
Other Name: Miralax

Drug: Fluconazole
Orally once daily (Day 1-14)
Other Name: Diflucan

Placebo Comparator: Placebo
Vancomycin oral suspension four times daily (Day 1-14), plus neomycin orally three times daily (Days 1-3), plus ciprofloxacin orally twice daily (Day 4-14), plus Polyethylene Glycol 3350 (Miralax) dissolved in Gatorade on day 2, plus placebo.
Drug: Vancomycin
Oral suspension 4 times daily (Day 1-14)
Other Name: Vancocin

Drug: Neomycin
Oral three times daily (Days 1-3)
Other Name: Neo-Fradin

Drug: Ciprofloxacin
Oral twice daily (Days 4-14)
Other Name: Cipro

Drug: Polyethylene Glycol 3350
Dissolved in Gatorade on day 2
Other Name: Miralax




Primary Outcome Measures :
  1. Change in disease activity by Pediatric Crohn's Disease Activity Index [ Time Frame: 15 days ]
    The primary endpoint will be the change in disease activity, as measured by Pediatric Crohn's Disease Activity Index (PCDAI) score, between the enrollment visit and Day 15. All participants who withdraw for any reason prior to day 15 will be considered treatment failures. The Pediatric Crohn's Disease Activity Index is a clinical score which takes into account general well being, degree of abdominal pain, number of liquid stools per day, abdominal physical examination, and Crohn's disease complications.

  2. Change in disease activity by fecal calprotectin (FCP) [ Time Frame: 15 days ]
    The second primary outcome measure will be the change in disease activity, as measured by fecal calprotectin, between the enrollment visit and day 15. The fecal calprotectin is a stool test which measures intestinal inflammation.


Secondary Outcome Measures :
  1. Change in C-reactive Protein (CRP) [ Time Frame: 15 days ]
    A secondary outcome measure will be the change in C-reactive protein between the enrollment visit and day 15. The C-reactive protein is a blood test which measures systemic inflammation.

  2. Safety and tolerability of the treatment regimen based on medication side effects and/or adverse events [ Time Frame: 105 days ]


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Ages Eligible for Study:   6 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females 6-18 years of age
  • Current weight >10 kg (or 22 lb)
  • Ability to swallow pills
  • Normal kidney function
  • Normal Aspartate transaminase (AST), Alanine transaminase (ALT), and alkaline phosphatase
  • Active CD defined as PCDAI ≥ 30
  • C-Reactive Protein (CRP) ≥ 15mg/L (or 1.5mg/dL) or fecal calprotectin (FCP)>350mcg/g (within one month of enrollment)
  • Have been treated with one of the following therapies for at least 8 weeks with primary nonresponse or an initial response, followed by loss of response [LOR] (self-reported worsening of symptoms for ≥ 7 days): azathioprine, 6-mercaptopurine, methotrexate, adalimumab, certolizumab, golimumab, infliximab, natalizumab, vedolizumab, or ustekinumab **These medications must have been administered at standard, therapeutic dosages.

Exclusion Criteria:

  • Known allergy or intolerance to aminoglycosides or any of the medications used in this study
  • Current use of one or more of the following medications: 5-fluorouracil, digoxin, anticoagulants, theophylline, phenytoin, probenecid, duloxetine, clozapine, sildenafil, hydrochlorothiazide, cyclosporine, hypoglycemics, terfenadine, tacrolimus, rifabutin, midazolam, and voriconazole
  • Known diagnosis of diabetes mellitus
  • Known or suspected structuring disease producing obstructive symptoms
  • Active Clostridium difficile infection
  • Prolonged QTc interval as seen on enrollment EKG
  • Current use of antibiotics
  • Starting or increasing the dose of an IBD related medication within 4 weeks of screening

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): NCT03476317


Contacts
Contact: Sarah Dozil 267-426-8414 DOZILS@email.chop.edu
Contact: IBDResearch IBDResearch@email.chop.edu

Locations
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19146
Contact: Lindsey G Aldenberg, MD    215-590-7801    ALBENBERGL@email.chop.edu   
Contact: Sarah Dozil    267-426-8414    DOZILS@email.chop.edu   
Sponsors and Collaborators
Children's Hospital of Philadelphia
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Lindsay Albenberg, DO Children's Hospital of Philadelphia

Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT03476317     History of Changes
Other Study ID Numbers: 17-014343
5K23DK109136-02 ( U.S. NIH Grant/Contract )
First Posted: March 26, 2018    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Vancomycin
Ciprofloxacin
Neomycin
Fluconazole
Polyethylene glycol 3350
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antifungal Agents
14-alpha Demethylase Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Laxatives
Gastrointestinal Agents