Crohn DiseasePhase 2HolidayNCT03476317
Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
A Phase 2 study testing Vancomycin, Neomycin and Ciprofloxacin in people with Crohn Disease, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Crohn Disease
- What is being tested?
- Vancomycin, Neomycin and Ciprofloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jul 2018to 31 Dec 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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.
- 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.
Who cannot join
- 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
Show all 14Show fewer
- Current use of antibiotics
- Starting or increasing the dose of an IBD related medication within 4 weeks of screening
- Group 2
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19146
About this study
Official title: An Open-Label Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
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.
Read the 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.
- Conditions
- Crohn Disease
- Being tested
- Vancomycin, Neomycin, Ciprofloxacin, Polyethylene Glycol 3350, Fluconazole
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VancomycinDrug
Also called Vancocin
Oral suspension 4 times daily (Day 1-14)
NeomycinDrug
Also called Neo-Fradin
Oral three times daily (Days 1-3)
CiprofloxacinDrug
Also called Cipro
Oral twice daily (Days 4-14)
Polyethylene Glycol 3350Drug
Also called Miralax
Dissolved in Gatorade on day 2
FluconazoleDrug
Also called Diflucan
Orally once daily (Day 1-14)
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline, Day 15
Secondary outcomes (2)
Change in C-reactive Protein (CRP)
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.
Measured: Baseline, Day 15
Safety and Tolerability of the Treatment Regimen Based on Medication Side Effects and/or Adverse Events
Measured: 105 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2018
- Study start12 Jul 2018
- Primary completion31 Dec 2020
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Lindsey Albenberg, DO, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03476317
- Sponsor's protocol ID
- 17-014343
- Other IDs
- 5K23DK109136-02
- Acronym
- Holiday
- Status last verified
- Feb 2022
- First submitted
- 8 Jan 2018
- Last updated
- 9 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Pilot Study of Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
- ClinicalTrials.gov ID
- NCT03476317
- Acronym / sponsor ID
- Holiday / 17-014343
- Conditions
- Crohn Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- University of Pennsylvania, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 12 Jul 2018 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 26 Mar 2018 (actual)
- Results
- Posted 9 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1-Fluconazole | Experimental | Drug: Vancomycin, Drug: Neomycin, Drug: Ciprofloxacin, Drug: Polyethylene Glycol 3350, Drug: FluconazoleVancomycin 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). |
| Group 1-Placebo | Placebo comparator | Drug: Vancomycin, Drug: Neomycin, Drug: Ciprofloxacin, Drug: Polyethylene Glycol 3350Vancomycin 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. |
| 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. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VancomycinAlso: VancocinOral suspension 4 times daily (Day 1-14) | Drug | Group 1-Fluconazole, Group 1-Placebo |
| NeomycinAlso: Neo-FradinOral three times daily (Days 1-3) | Drug | Group 1-Fluconazole, Group 1-Placebo |
| CiprofloxacinAlso: CiproOral twice daily (Days 4-14) | Drug | Group 1-Fluconazole, Group 1-Placebo |
| Polyethylene Glycol 3350Also: MiralaxDissolved in Gatorade on day 2 | Drug | Group 1-Fluconazole, Group 1-Placebo |
| FluconazoleAlso: DiflucanOrally once daily (Day 1-14) | Drug | Group 1-Fluconazole |
Primary outcome
Change in FCP in Group 2 Participants
Time frame: change from baseline to day 12
Change in fecal calprotectin between stool samples collected at baseline and day 12 after procedure in Group 2 participants.
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.
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.
2 secondary outcomes
Change in C-reactive Protein (CRP)
Time frame: Baseline, Day 15
Safety and Tolerability of the Treatment Regimen Based on Medication Side Effects and/or Adverse Events
Time frame: 105 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lindsey Albenberg, DO principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vancomycin, Neomycin and Ciprofloxacin in people with Crohn Disease, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in FCP in Group 2 Participants (time frame: change from baseline to day 12). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2022.