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

Primary Purpose

Crohn Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Vancomycin
Neomycin
Ciprofloxacin
Polyethylene Glycol 3350
Fluconazole
Sponsored by
Children's Hospital of Philadelphia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Crohn Disease

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Group 1

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.

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

Inclusion Criteria

  • 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

  • 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.

Sites / Locations

  • Children's Hospital of Philadelphia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

No Intervention

Arm Label

Group 1-Fluconazole

Group 1-Placebo

Group 2

Arm Description

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).

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.

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

Outcomes

Primary Outcome Measures

Change in FCP in Group 2 Participants
Change in fecal calprotectin between stool samples collected at baseline and day 12 after procedure in Group 2 participants.
Change in Disease Activity by Pediatric Crohn's Disease Activity Index
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.
Change in Disease Activity by Fecal Calprotectin (FCP)
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

Change in C-reactive Protein (CRP)
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.
Safety and Tolerability of the Treatment Regimen Based on Medication Side Effects and/or Adverse Events

Full Information

First Posted
January 8, 2018
Last Updated
February 8, 2022
Sponsor
Children's Hospital of Philadelphia
Collaborators
University of Pennsylvania, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT03476317
Brief Title
Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
Acronym
Holiday
Official Title
An Open-Label Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
July 12, 2018 (Actual)
Primary Completion Date
December 31, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital of Philadelphia
Collaborators
University of Pennsylvania, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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) 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1-Fluconazole
Arm Type
Experimental
Arm Description
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).
Arm Title
Group 1-Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Group 2
Arm Type
No Intervention
Arm Description
Collect stool samples for calprotectin in patients undergoing colonoscopy for clinical care to evaluate effect of bowel lavage alone on calprotectin.
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Other Intervention Name(s)
Vancocin
Intervention Description
Oral suspension 4 times daily (Day 1-14)
Intervention Type
Drug
Intervention Name(s)
Neomycin
Other Intervention Name(s)
Neo-Fradin
Intervention Description
Oral three times daily (Days 1-3)
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin
Other Intervention Name(s)
Cipro
Intervention Description
Oral twice daily (Days 4-14)
Intervention Type
Drug
Intervention Name(s)
Polyethylene Glycol 3350
Other Intervention Name(s)
Miralax
Intervention Description
Dissolved in Gatorade on day 2
Intervention Type
Drug
Intervention Name(s)
Fluconazole
Other Intervention Name(s)
Diflucan
Intervention Description
Orally once daily (Day 1-14)
Primary Outcome Measure Information:
Title
Change in FCP in Group 2 Participants
Description
Change in fecal calprotectin between stool samples collected at baseline and day 12 after procedure in Group 2 participants.
Time Frame
change from baseline to day 12
Title
Change in Disease Activity by Pediatric Crohn's Disease Activity Index
Description
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.
Time Frame
Baseline, Day 15
Title
Change in Disease Activity by Fecal Calprotectin (FCP)
Description
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.
Time Frame
Baseline, Day 15
Secondary Outcome Measure Information:
Title
Change in C-reactive Protein (CRP)
Description
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.
Time Frame
Baseline, Day 15
Title
Safety and Tolerability of the Treatment Regimen Based on Medication Side Effects and/or Adverse Events
Time Frame
105 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Group 1 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. 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 Inclusion Criteria 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lindsey Albenberg, DO
Organizational Affiliation
Children's Hospital of Philadelphia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19146
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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