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

Primary Purpose

Crohn's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fluconazole
Vancomycin
Neomycin
Ciprofloxacin
Polyethylene Glycol 3350
Promethazine
Fluconazole placebo
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Crohn's Disease

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participant is capable of giving informed consent
  • Males or females 18-75 years of age
  • Normal kidney function (defined by normal serum creatinine [male: <1.27 mg/dL; female: <1.03 mg/dL])
  • Normal aspartate aminotransferase [AST] (<41 U/L), alanine aminotransferase [ALT] (<63 U/L), and alkaline phosphatase (<126 U/L)
  • Active CD defined as HBI ≥ 7
  • CRP > 5 mg/dL or hs-CRP > 10mg/L (or 1mg/dL) or fecal calprotectin (FCP) > - - 350 mcg/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 or suspected stricturing disease producing obstructive symptoms
  • Active Clostridium difficile infection
  • Unwillingness to provide informed consent
  • Allergy or intolerance to the medications used in this study
  • History of kidney disease
  • History of liver disease
  • Pregnant or lactating females
  • Baseline QTc interval on EKG > 430 in males or > 450 in females
  • Participants who, in the opinion of the investigator, may be non-compliant with study schedules or procedures

Sites / Locations

  • University of Pennsylvania

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Fluconazole

Placebo

Arm Description

Vancomycin 500 mg oral suspension four times daily (Day 1-14), plus neomycin 1000 mg orally three times daily (Days 1-3), plus ciprofloxacin 750 mg orally twice daily (Day 4-14), plus Polyethylene Glycol 3350 (Miralax) 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2, plus fluconazole 400 mg orally once daily (Day 1-14). PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).

Vancomycin 500 mg oral suspension four times daily (Day 1-14), plus neomycin 1000 mg orally three times daily (Days 1-3), plus ciprofloxacin 750 mg orally twice daily (Day 4-14), plus Polyethylene Glycol 3350 (Miralax) 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2, plus placebo for fluconazole. PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).

Outcomes

Primary Outcome Measures

Change in Disease Activity by Harvey Bradshaw Index
The primary endpoint will be the change in disease activity, as measured by Harvey-Bradshaw Index (HBI) 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 HBI is a clinical score where points are given for each category below plus number of liquid bowel movements in previous day. A score of 3 or lower is considered remission. A score of 8 or higher is considered severe disease. General Well Being Very well 0 points Slightly below par 1 point Poor 2 points Very poor 3 points Terrible 4 points Abdominal Pain None 0 points Mild 1 point Moderate 2 points Severe 3 points Abdominal Mass None 0 points Dubious 1 point Definite 2 points Definite and tender 3 points Complications None 0 points Arthralgias +1 point Uveitis +1 point Erythema Nodosum + 1 point Aphthous ulcers +1 point Pyoderma Gangrenosum + 1 point Anal fissure + 1 point New fistula + 1
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

The Change in High-sensitivity C-reactive Protein (hsCRP)
A secondary outcome measure will be the change in high-sensitivity C-reactive protein between the enrollment visit and day 15. The high-sensitivity 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 (AEs).
Number of Medication Side Effects and/or Adverse Events (AEs)

Full Information

First Posted
May 2, 2016
Last Updated
February 4, 2021
Sponsor
University of Pennsylvania
Collaborators
Children's Hospital of Philadelphia, Crohn's and Colitis Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT02765256
Brief Title
Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
Acronym
Holiday
Official Title
Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
August 2016 (undefined)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania
Collaborators
Children's Hospital of Philadelphia, Crohn's and Colitis Foundation

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Fluconazole
Arm Type
Experimental
Arm Description
Vancomycin 500 mg oral suspension four times daily (Day 1-14), plus neomycin 1000 mg orally three times daily (Days 1-3), plus ciprofloxacin 750 mg orally twice daily (Day 4-14), plus Polyethylene Glycol 3350 (Miralax) 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2, plus fluconazole 400 mg orally once daily (Day 1-14). PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Vancomycin 500 mg oral suspension four times daily (Day 1-14), plus neomycin 1000 mg orally three times daily (Days 1-3), plus ciprofloxacin 750 mg orally twice daily (Day 4-14), plus Polyethylene Glycol 3350 (Miralax) 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2, plus placebo for fluconazole. PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Intervention Type
Drug
Intervention Name(s)
Fluconazole
Other Intervention Name(s)
Diflucan
Intervention Description
400mg orally once daily (Day 1-14)
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Other Intervention Name(s)
Vancocin
Intervention Description
500mg oral suspension 4 times daily (Day 1-14)
Intervention Type
Drug
Intervention Name(s)
Neomycin
Other Intervention Name(s)
Neo-Fradin
Intervention Description
neomycin 1000 mg orally three times daily (Days 1-3)
Intervention Type
Drug
Intervention Name(s)
Ciprofloxacin
Other Intervention Name(s)
Cipro
Intervention Description
ciprofloxacin 750 mg orally twice daily (Day 4-14)
Intervention Type
Drug
Intervention Name(s)
Polyethylene Glycol 3350
Other Intervention Name(s)
Miralax
Intervention Description
238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Intervention Type
Drug
Intervention Name(s)
Promethazine
Other Intervention Name(s)
Phenergan
Intervention Description
PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Intervention Type
Drug
Intervention Name(s)
Fluconazole placebo
Intervention Description
Once daily
Primary Outcome Measure Information:
Title
Change in Disease Activity by Harvey Bradshaw Index
Description
The primary endpoint will be the change in disease activity, as measured by Harvey-Bradshaw Index (HBI) 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 HBI is a clinical score where points are given for each category below plus number of liquid bowel movements in previous day. A score of 3 or lower is considered remission. A score of 8 or higher is considered severe disease. General Well Being Very well 0 points Slightly below par 1 point Poor 2 points Very poor 3 points Terrible 4 points Abdominal Pain None 0 points Mild 1 point Moderate 2 points Severe 3 points Abdominal Mass None 0 points Dubious 1 point Definite 2 points Definite and tender 3 points Complications None 0 points Arthralgias +1 point Uveitis +1 point Erythema Nodosum + 1 point Aphthous ulcers +1 point Pyoderma Gangrenosum + 1 point Anal fissure + 1 point New fistula + 1
Time Frame
enrollment visit (baseline) and 15 days
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
enrollment visit (baseline) and 15 days
Secondary Outcome Measure Information:
Title
The Change in High-sensitivity C-reactive Protein (hsCRP)
Description
A secondary outcome measure will be the change in high-sensitivity C-reactive protein between the enrollment visit and day 15. The high-sensitivity C-reactive protein is a blood test which measures systemic inflammation.
Time Frame
enrollment visit (baseline) and 15 days
Title
Safety and Tolerability of the Treatment Regimen Based on Medication Side Effects and/or Adverse Events (AEs).
Description
Number of Medication Side Effects and/or Adverse Events (AEs)
Time Frame
105 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participant is capable of giving informed consent Males or females 18-75 years of age Normal kidney function (defined by normal serum creatinine [male: <1.27 mg/dL; female: <1.03 mg/dL]) Normal aspartate aminotransferase [AST] (<41 U/L), alanine aminotransferase [ALT] (<63 U/L), and alkaline phosphatase (<126 U/L) Active CD defined as HBI ≥ 7 CRP > 5 mg/dL or hs-CRP > 10mg/L (or 1mg/dL) or fecal calprotectin (FCP) > - - 350 mcg/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 or suspected stricturing disease producing obstructive symptoms Active Clostridium difficile infection Unwillingness to provide informed consent Allergy or intolerance to the medications used in this study History of kidney disease History of liver disease Pregnant or lactating females Baseline QTc interval on EKG > 430 in males or > 450 in females Participants 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
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
James D Lewis, MD, MSCE
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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