Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03476317
Recruitment Status : Active, not recruiting
First Posted : March 26, 2018
Last Update Posted : April 14, 2020
Sponsor:
Collaborators:
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Brief Summary:
The purpose of this study is 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) or indeterminate colitis (IBDU) that is refractory to conventional, immunosuppressive therapy. In addition, the study will determine the effect of PEG lavage alone on fecal calprotectin and gut microbiota in patients who are undergoing a PEG lavage for clinical care.

Condition or disease Intervention/treatment Phase
Crohn Disease Drug: Vancomycin Drug: Neomycin Drug: Ciprofloxacin Drug: Polyethylene Glycol 3350 Drug: Fluconazole Phase 2

Detailed Description:

Investigators will evaluate the efficacy of a novel treatment regimen, employing non-immunosuppressive medications, in the management of refractory CD or IBDU. Refractory patients include those patients who have experienced loss of responsiveness (LOR) or primary nonresponse to an immunomodulator or a biologic. Investigators will treat participants with a combination of gut microbiota-targeted therapies to restore a healthy gut microbiome composition. Investigators believe that this strategy will both treat the gut inflammation associated with inflammatory bowel disease (IBD) as well as salvage response to immune suppressive therapies.

Investigators will also evaluate the effect of PEG lavage alone on fecal calprotectin and gut microbiota. Participants in this arm, will be undergoing a PEG lavage in preparation for a endoscopy for clinical care. They will be asked to provide stool samples, prior to and after their PEG lavage. Participants will not be receiving any investigational treatments.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Open-Label Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
Actual Study Start Date : July 12, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Arm Intervention/treatment
Experimental: Group 1-Fluconazole
Vancomycin oral suspension four times daily (Day 1-14), plus neomycin orally three times daily (Days 1-3), plus ciprofloxacin orally twice daily (Day 4-14), plus Polyethylene Glycol 3350 (Miralax) dissolved in Gatorade on day 2, plus fluconazole orally once daily (Day 1-14).
Drug: Vancomycin
Oral suspension 4 times daily (Day 1-14)
Other Name: Vancocin

Drug: Neomycin
Oral three times daily (Days 1-3)
Other Name: Neo-Fradin

Drug: Ciprofloxacin
Oral twice daily (Days 4-14)
Other Name: Cipro

Drug: Polyethylene Glycol 3350
Dissolved in Gatorade on day 2
Other Name: Miralax

Drug: Fluconazole
Orally once daily (Day 1-14)
Other Name: Diflucan

Placebo Comparator: Group 1-Placebo
Vancomycin oral suspension four times daily (Day 1-14), plus neomycin orally three times daily (Days 1-3), plus ciprofloxacin orally twice daily (Day 4-14), plus Polyethylene Glycol 3350 (Miralax) dissolved in Gatorade on day 2, plus placebo.
Drug: Vancomycin
Oral suspension 4 times daily (Day 1-14)
Other Name: Vancocin

Drug: Neomycin
Oral three times daily (Days 1-3)
Other Name: Neo-Fradin

Drug: Ciprofloxacin
Oral twice daily (Days 4-14)
Other Name: Cipro

Drug: Polyethylene Glycol 3350
Dissolved in Gatorade on day 2
Other Name: Miralax

No Intervention: Group 2



Primary Outcome Measures :
  1. Change in disease activity by Pediatric Crohn's Disease Activity Index [ Time Frame: Baseline, Day 15 ]
    The primary endpoint will be the change in disease activity, as measured by Pediatric Crohn's Disease Activity Index (PCDAI) 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 Pediatric Crohn's Disease Activity Index is a clinical score which takes into account general well being, degree of abdominal pain, number of liquid stools per day, abdominal physical examination, and Crohn's disease complications.

  2. Change in disease activity by fecal calprotectin (FCP) [ Time Frame: Baseline, Day 15 ]
    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 :
  1. Change in C-reactive Protein (CRP) [ Time Frame: Baseline, Day 15 ]
    A secondary outcome measure will be the change in C-reactive protein between the enrollment visit and day 15. The C-reactive protein is a blood test which measures systemic inflammation.

  2. Safety and tolerability of the treatment regimen based on medication side effects and/or adverse events [ Time Frame: 105 days ]
  3. Change in FCP in Group 2 participants [ Time Frame: Baseline, Day 5 after procedure, and Day 12 after procedure in Group 2 participants ]
    A secondary outcome measure will be the change in fecal calprotectin between stool samples collected at baseline, Day 5 after procedure and Day 12 after procedure in Group 2 participants.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Group 1

Inclusion Criteria:

  • Males or females 6-18 years of age
  • Current weight >10 kg (or 22 lb)
  • Ability to swallow pills
  • Normal kidney function
  • Normal Aspartate transaminase (AST), Alanine transaminase (ALT), and alkaline phosphatase
  • Active CD or IBDU defined as PCDAI ≥ 30
  • C-Reactive Protein (CRP) ≥ 15mg/L (or 1.5mg/dL) or fecal calprotectin (FCP)>350mcg/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 allergy or intolerance to aminoglycosides or any of the medications used in this study
  • Current use of one or more of the following medications: 5-fluorouracil, digoxin, anticoagulants, theophylline, phenytoin, probenecid, duloxetine, clozapine, sildenafil, hydrochlorothiazide, cyclosporine, hypoglycemics, terfenadine, tacrolimus, rifabutin, midazolam, and voriconazole
  • Known diagnosis of diabetes mellitus
  • Known or suspected structuring disease producing obstructive symptoms
  • Active Clostridium difficile infection
  • Prolonged QTc interval as seen on enrollment EKG
  • Current use of antibiotics
  • Starting or increasing the dose of an IBD related medication within 4 weeks of screening

Group 2

Inclusion Criteria

  • Males or females 10 years of age and older.
  • Patients undergoing a clinical GI endoscopy due to suspicion for active intestinal inflammation determined by physician global assessment (PGA).
  • Undergoing a bowel preparation as part of clinical care.
  • Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria

  • Antibiotic use within the past 30 days.
  • Current presence of an ostomy bag.
  • Patients undergoing a non- polyethylene glycol 3350 cleanout.
  • Unwillingness to provide informed consent.
  • Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03476317


Locations
Layout table for location information
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19146
Sponsors and Collaborators
Children's Hospital of Philadelphia
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Layout table for investigator information
Principal Investigator: Lindsay Albenberg, DO Children's Hospital of Philadelphia
Layout table for additonal information
Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT03476317    
Other Study ID Numbers: 17-014343
5K23DK109136-02 ( U.S. NIH Grant/Contract )
First Posted: March 26, 2018    Key Record Dates
Last Update Posted: April 14, 2020
Last Verified: April 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Vancomycin
Ciprofloxacin
Neomycin
Fluconazole
Polyethylene glycol 3350
Anti-Bacterial Agents
Anti-Infective Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antifungal Agents
14-alpha Demethylase Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Laxatives
Gastrointestinal Agents