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

University of Pennsylvania

Status and phase: Completed; Phase 2

Conditions: Crohn's Disease

Treatments: Drug: Neomycin; Drug: Promethazine; Drug: Fluconazole placebo; Drug: Polyethylene Glycol 3350; Drug: Ciprofloxacin; Drug: Fluconazole; Drug: Vancomycin

Study type: Interventional

Funder types: Other

Identifiers

NCT02765256

823635

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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8 participants in 2 patient groups, including a placebo group

Fluconazole

Experimental group

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).

Treatment:

Drug: Vancomycin

Drug: Polyethylene Glycol 3350

Drug: Ciprofloxacin

Drug: Fluconazole

Drug: Promethazine

Drug: Neomycin

Placebo

Placebo Comparator group

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).

Treatment:

Drug: Fluconazole placebo

Drug: Vancomycin

Drug: Polyethylene Glycol 3350

Drug: Ciprofloxacin

Drug: Promethazine

Drug: Neomycin