Clinical trial NCT03476317: Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
Official title: An Open-Label Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Crohn Disease
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2018-03-26
Enrollment: 10
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Change in FCP in Group 2 Participants
timeFrame: change from baseline to day 12
measure: Change in Disease Activity by Pediatric Crohn's Disease Activity Index
timeFrame: Baseline, Day 15
measure: Change in Disease Activity by Fecal Calprotectin (FCP)
timeFrame: Baseline, Day 15
Secondary outcomes:
measure: Change in C-reactive Protein (CRP)
timeFrame: Baseline, Day 15
measure: Safety and Tolerability of the Treatment Regimen Based on Medication Side Effects and/or Adverse Events
timeFrame: 105 days
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Lindsey Albenberg, DO
role: PRINCIPAL_INVESTIGATOR
References: