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

NCT ID: NCT02765256

Last Updated: 2024-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2018-12-31

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.

Conditions

Crohn's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Fluconazole

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).

Group Type: EXPERIMENTAL

Fluconazole

Intervention Type: DRUG

400mg orally once daily (Day 1-14)

Vancomycin

Intervention Type: DRUG

500mg oral suspension 4 times daily (Day 1-14)

Neomycin

Intervention Type: DRUG

neomycin 1000 mg orally three times daily (Days 1-3)

Ciprofloxacin

Intervention Type: DRUG

ciprofloxacin 750 mg orally twice daily (Day 4-14)

Polyethylene Glycol 3350

Intervention Type: DRUG

238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2

Promethazine

Intervention Type: DRUG

PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).

Placebo

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).

Group Type: PLACEBO_COMPARATOR

Vancomycin

Intervention Type: DRUG

500mg oral suspension 4 times daily (Day 1-14)

Neomycin

Intervention Type: DRUG

neomycin 1000 mg orally three times daily (Days 1-3)

Ciprofloxacin

Intervention Type: DRUG

ciprofloxacin 750 mg orally twice daily (Day 4-14)

Polyethylene Glycol 3350

Intervention Type: DRUG

238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2

Promethazine

Intervention Type: DRUG

PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).

Fluconazole placebo

Intervention Type: DRUG

Once daily

Interventions

Fluconazole

400mg orally once daily (Day 1-14)

Intervention Type: DRUG

Vancomycin

500mg oral suspension 4 times daily (Day 1-14)

Intervention Type: DRUG

Neomycin

neomycin 1000 mg orally three times daily (Days 1-3)

Intervention Type: DRUG

Ciprofloxacin

ciprofloxacin 750 mg orally twice daily (Day 4-14)

Intervention Type: DRUG

Polyethylene Glycol 3350

238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2

Intervention Type: DRUG

Promethazine

PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).

Intervention Type: DRUG

Fluconazole placebo

Once daily

Intervention Type: DRUG

Other Intervention Names

Diflucan; Vancocin; Neo-Fradin; Cipro; Miralax; Phenergan

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

Crohn's and Colitis Foundation

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Lindsey Albenberg

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lindsey Albenberg, DO

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

James D Lewis, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

823635

Identifier Type: -

Identifier Source: org_study_id