Crohn's DiseasePhase 2HolidayNCT02765256
Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
A Phase 2 study testing Fluconazole, Vancomycin and Neomycin in people with Crohn's Disease, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- Fluconazole, Vancomycin and Neomycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2016to Dec 2018
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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
- Being tested
- Fluconazole, Vancomycin, Neomycin, Ciprofloxacin, Polyethylene Glycol 3350
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluconazoleDrug
Also called Diflucan
400mg orally once daily (Day 1-14)
VancomycinDrug
Also called Vancocin
500mg oral suspension 4 times daily (Day 1-14)
NeomycinDrug
Also called Neo-Fradin
neomycin 1000 mg orally three times daily (Days 1-3)
CiprofloxacinDrug
Also called Cipro
ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350Drug
Also called Miralax
238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
PromethazineDrug
Also called Phenergan
PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Fluconazole placeboDrug
Once daily
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: Vancomycin; Drug: Neomycin; Drug: Ciprofloxacin; Drug: Polyethylene Glycol 3350; Drug: Promethazine; Drug: Fluconazole placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: enrollment visit (baseline) and 15 days
Secondary outcomes (2)
The Change in High-sensitivity C-reactive Protein (hsCRP)
A secondary outcome measure will be the change in high-sensitivity C-reactive protein between the enrollment visit and day 15. The high-sensitivity C-reactive protein is a blood test which measures systemic inflammation.
Measured: enrollment visit (baseline) and 15 days
Safety and Tolerability of the Treatment Regimen Based on Medication Side Effects and/or Adverse Events (AEs).
Number of Medication Side Effects and/or Adverse Events (AEs)
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 posted6 May 2016 (estimated)
- Study startAug 2016
- Primary completionDec 2018
- Study completionDec 2018
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's DiseaseStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe 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
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital of Philadelphia, Crohn's and Colitis Foundation
- Responsible party
- Principal investigator, Lindsey Albenberg, University of Pennsylvania
- Investigators
- Lindsey Albenberg, DO, Principal investigator, University of PennsylvaniaJames D Lewis, MD, MSCE, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02765256
- Sponsor's protocol ID
- 823635
- Acronym
- Holiday
- Status last verified
- Feb 2024
- First submitted
- 2 May 2016
- Last updated
- 6 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease
- ClinicalTrials.gov ID
- NCT02765256
- Acronym / sponsor ID
- Holiday / 823635
- Conditions
- Crohn's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Children's Hospital of Philadelphia, Crohn's and Colitis Foundation
- Study start
- Aug 2016
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 6 May 2016 (estimated)
- Results
- Posted 8 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluconazole | Experimental | Drug: Fluconazole, Drug: Vancomycin, Drug: Neomycin, Drug: Ciprofloxacin, Drug: Polyethylene Glycol 3350, Drug: PromethazineVancomycin 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). |
| Placebo | Placebo comparator | Drug: Vancomycin, Drug: Neomycin, Drug: Ciprofloxacin, Drug: Polyethylene Glycol 3350, Drug: Promethazine, Drug: Fluconazole placeboVancomycin 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- 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
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 |
|---|---|---|
| FluconazoleAlso: Diflucan400mg orally once daily (Day 1-14) | Drug | Fluconazole |
| VancomycinAlso: Vancocin500mg oral suspension 4 times daily (Day 1-14) | Drug | Fluconazole, Placebo |
| NeomycinAlso: Neo-Fradinneomycin 1000 mg orally three times daily (Days 1-3) | Drug | Fluconazole, Placebo |
| CiprofloxacinAlso: Ciprociprofloxacin 750 mg orally twice daily (Day 4-14) | Drug | Fluconazole, Placebo |
| Polyethylene Glycol 3350Also: Miralax238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2 | Drug | Fluconazole, Placebo |
| PromethazineAlso: PhenerganPRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3). | Drug | Fluconazole, Placebo |
| Fluconazole placeboOnce daily | Drug | Placebo |
Primary outcome
Change in Disease Activity by Harvey Bradshaw Index
Time frame: enrollment visit (baseline) and 15 days
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
Change in Disease Activity by Fecal Calprotectin (FCP)
Time frame: enrollment visit (baseline) and 15 days
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
The Change in High-sensitivity C-reactive Protein (hsCRP)
Time frame: enrollment visit (baseline) and 15 days
Safety and Tolerability of the Treatment Regimen Based on Medication Side Effects and/or Adverse Events (AEs).
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 6 Feb 2024.
- 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
University of Pennsylvania
James D Lewis, MD, MSCE principal investigator
University of Pennsylvania
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 Fluconazole, Vancomycin and Neomycin in people with Crohn's Disease, run by University of Pennsylvania 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 7 inclusion and 9 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 6 Feb 2024. 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 8 Feb 2021). 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 Disease Activity by Harvey Bradshaw Index (time frame: enrollment visit (baseline) and 15 days). The study lists 2 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 6 Feb 2024.