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

NCT03476317 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 17-0143435K23DK109136-02
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Crohn Disease

Outcome Measures

Primary Outcomes (3)

• Change in FCP in Group 2 Participants

  Change in fecal calprotectin between stool samples collected at baseline and day 12 after procedure in Group 2 participants.

  change from baseline to day 12

• Change in Disease Activity by Pediatric Crohn's Disease Activity Index

  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.

  Baseline, Day 15

• 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.

  Baseline, Day 15

Secondary Outcomes (2)

• Change in C-reactive Protein (CRP)

  Baseline, Day 15

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

  105 days

Study Arms (3)

Group 1-Fluconazole

EXPERIMENTAL

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

Group 1-Placebo

PLACEBO COMPARATOR

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; Drug: Neomycin; Drug: Ciprofloxacin; Drug: Polyethylene Glycol 3350

Group 2

NO INTERVENTION

Collect stool samples for calprotectin in patients undergoing colonoscopy for clinical care to evaluate effect of bowel lavage alone on calprotectin.

Interventions

Vancomycin DRUG

Oral suspension 4 times daily (Day 1-14)

Also known as: Vancocin

Group 1-Fluconazole; Group 1-Placebo

Neomycin DRUG

Oral three times daily (Days 1-3)

Also known as: Neo-Fradin

Group 1-Fluconazole; Group 1-Placebo

Ciprofloxacin DRUG

Oral twice daily (Days 4-14)

Also known as: Cipro

Group 1-Fluconazole; Group 1-Placebo

Polyethylene Glycol 3350 DRUG

Dissolved in Gatorade on day 2

Also known as: Miralax

Group 1-Fluconazole; Group 1-Placebo

Fluconazole DRUG

Orally once daily (Day 1-14)

Also known as: Diflucan

Group 1-Fluconazole

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.
• Antibiotic use within the past 30 days.
• Current presence of an ostomy bag.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• University of Pennsylvania: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19146, United States

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

Vancomycin; Neomycin; Ciprofloxacin; polyethylene glycol 3350; Fluconazole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Aminoglycosides; Glycosides; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Group 1 study was not completed.

Results Point of Contact

• Title: Lindsey Albenberg, DO
• Organization: Children's Hospital of Philadelphia

albenbergl@chop.edu

267-426-0139

Study Officials

• Lindsey Albenberg, DO

  Children's Hospital of Philadelphia

  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: SPONSOR

Study Record Dates

• First Submitted: January 8, 2018
• First Posted: March 26, 2018
• Study Start: July 12, 2018
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: February 9, 2022
• Results First Posted: February 9, 2022

Record last verified: 2022-02

Locations

US (1)