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

NCT02765256 | Completed Phase 2 Results

• 1 other identifier: 823635
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• The Change in High-sensitivity C-reactive Protein (hsCRP)

  enrollment visit (baseline) and 15 days

• Safety and Tolerability of the Treatment Regimen Based on Medication Side Effects and/or Adverse Events (AEs).

  105 days

Study Arms (2)

Fluconazole

EXPERIMENTAL

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).

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

Placebo

PLACEBO COMPARATOR

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).

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

Interventions

Fluconazole DRUG

400mg orally once daily (Day 1-14)

Also known as: Diflucan

Fluconazole

Vancomycin DRUG

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

Also known as: Vancocin

Fluconazole; Placebo

Neomycin DRUG

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

Also known as: Neo-Fradin

Fluconazole; Placebo

Ciprofloxacin DRUG

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

Also known as: Cipro

Fluconazole; Placebo

Polyethylene Glycol 3350 DRUG

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

Also known as: Miralax

Fluconazole; Placebo

Promethazine DRUG

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

Also known as: Phenergan

Fluconazole; Placebo

Fluconazole placebo DRUG

Once daily

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• Children's Hospital of Philadelphia: collaborator
• Crohn's and Colitis Foundation: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

Fluconazole; Vancomycin; Neomycin; Ciprofloxacin; polyethylene glycol 3350; Promethazine

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Aminoglycosides; Glycosides; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Propylamines; Amines; Organic Chemicals; Phenothiazines; Sulfur Compounds; Heterocyclic Compounds, 3-Ring

Limitations and Caveats

Recruitment was difficult due to intensive methods with large number of/frequent study visits required. Small sample size is a major limitation.

Results Point of Contact

• Title: Lindsey Albenberg, DO
• Organization: University of Pennsylvania

albenbergl@email.chop.edu

267-426-0139

Study Officials

• Lindsey Albenberg, DO

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• James D Lewis, MD, MSCE

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: May 2, 2016
• First Posted: May 6, 2016
• Study Start: August 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: February 6, 2024
• Results First Posted: February 8, 2021

Record last verified: 2024-02

Locations

US (1)