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

NCT ID: NCT03476317

Last Updated: 2022-02-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-12

Study Completion Date

2020-12-31

Brief Summary

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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) or indeterminate colitis (IBDU) that is refractory to conventional, immunosuppressive therapy. In addition, the study will determine the effect of PEG lavage alone on fecal calprotectin and gut microbiota in patients who are undergoing a PEG lavage for clinical care.

Detailed Description

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Investigators will evaluate the efficacy of a novel treatment regimen, employing non-immunosuppressive medications, in the management of refractory CD or IBDU. 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.

Investigators will also evaluate the effect of PEG lavage alone on fecal calprotectin and gut microbiota. Participants in this arm, will be undergoing a PEG lavage in preparation for a endoscopy for clinical care. They will be asked to provide stool samples, prior to and after their PEG lavage. Participants will not be receiving any investigational treatments.

Conditions

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Crohn Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group 1-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).

Group Type EXPERIMENTAL

Vancomycin

Intervention Type DRUG

Oral suspension 4 times daily (Day 1-14)

Neomycin

Intervention Type DRUG

Oral three times daily (Days 1-3)

Ciprofloxacin

Intervention Type DRUG

Oral twice daily (Days 4-14)

Polyethylene Glycol 3350

Intervention Type DRUG

Dissolved in Gatorade on day 2

Fluconazole

Intervention Type DRUG

Orally once daily (Day 1-14)

Group 1-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.

Group Type PLACEBO_COMPARATOR

Vancomycin

Intervention Type DRUG

Oral suspension 4 times daily (Day 1-14)

Neomycin

Intervention Type DRUG

Oral three times daily (Days 1-3)

Ciprofloxacin

Intervention Type DRUG

Oral twice daily (Days 4-14)

Polyethylene Glycol 3350

Intervention Type DRUG

Dissolved in Gatorade on day 2

Group 2

Collect stool samples for calprotectin in patients undergoing colonoscopy for clinical care to evaluate effect of bowel lavage alone on calprotectin.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Vancomycin

Oral suspension 4 times daily (Day 1-14)

Intervention Type DRUG

Neomycin

Oral three times daily (Days 1-3)

Intervention Type DRUG

Ciprofloxacin

Oral twice daily (Days 4-14)

Intervention Type DRUG

Polyethylene Glycol 3350

Dissolved in Gatorade on day 2

Intervention Type DRUG

Fluconazole

Orally once daily (Day 1-14)

Intervention Type DRUG

Other Intervention Names

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Vancocin Neo-Fradin Cipro Miralax Diflucan

Eligibility Criteria

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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 or IBDU 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.


* Males or females 10 years of age and older.
* Patients undergoing a clinical GI endoscopy due to suspicion for active intestinal inflammation determined by physician global assessment (PGA).
* Undergoing a bowel preparation as part of clinical care.
* Parental/guardian permission (informed consent) and if appropriate, child assent.

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

Group 2


* Antibiotic use within the past 30 days.
* Current presence of an ostomy bag.
* Patients undergoing a non- polyethylene glycol 3350 cleanout.
* Unwillingness to provide informed consent.
* Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
Minimum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Pennsylvania

OTHER

Sponsor Role collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lindsey Albenberg, DO

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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5K23DK109136-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

17-014343

Identifier Type: -

Identifier Source: org_study_id

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