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

Crohn's Disease Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02765256
• Other study ID #: 823635
• Status: Completed
• Phase: Phase 2
• Start date: August 2016
• Est. completion date: December 2018

Study information

• Verified date: February 2024
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Crohn's Disease

Intervention

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

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
University of Pennsylvania	Children's Hospital of Philadelphia, Crohn's and Colitis Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	enrollment visit (baseline) and 15 days
Primary	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.	enrollment visit (baseline) and 15 days
Secondary	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.	enrollment visit (baseline) and 15 days
Secondary	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)	105 days