Trial Outcomes & Findings for Fundamental Modification of the Gut Microbiota in the Treatment of Refractory Crohn's Disease (NCT NCT02765256)
NCT ID: NCT02765256
Last Updated: 2024-02-06
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
8 participants
Primary outcome timeframe
enrollment visit (baseline) and 15 days
Results posted on
2024-02-06
Participant Flow
Participant milestones
| Measure |
Fluconazole
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).
Fluconazole: 400mg orally once daily (Day 1-14)
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
|
Placebo
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).
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Fluconazole placebo: Once daily
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
4
|
|
Overall Study
COMPLETED
|
4
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Fluconazole
n=4 Participants
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).
Fluconazole: 400mg orally once daily (Day 1-14)
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
|
Placebo
n=4 Participants
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).
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Fluconazole placebo: Once daily
|
Total
n=8 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
44 years
n=4 Participants
|
32.5 years
n=4 Participants
|
39.5 years
n=8 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=4 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=4 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=8 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
4 participants
n=4 Participants
|
4 participants
n=4 Participants
|
8 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: enrollment visit (baseline) and 15 daysThe 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
Outcome measures
| Measure |
Fluconazole
n=4 Participants
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).
Fluconazole: 400mg orally once daily (Day 1-14)
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
|
Placebo
n=4 Participants
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).
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Fluconazole placebo: Once daily
|
|---|---|---|
|
Change in Disease Activity by Harvey Bradshaw Index
|
-5 score on a scale
Interval -7.0 to 0.0
|
-3 score on a scale
Interval -8.0 to -2.0
|
PRIMARY outcome
Timeframe: enrollment visit (baseline) and 15 daysThe 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.
Outcome measures
| Measure |
Fluconazole
n=4 Participants
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).
Fluconazole: 400mg orally once daily (Day 1-14)
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
|
Placebo
n=4 Participants
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).
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Fluconazole placebo: Once daily
|
|---|---|---|
|
Change in Disease Activity by Fecal Calprotectin (FCP)
|
-16.5 mcg/g
Interval -116.48 to 94.0
|
-380.5 mcg/g
Interval -1234.0 to -1.0
|
SECONDARY outcome
Timeframe: enrollment visit (baseline) and 15 daysA 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.
Outcome measures
| Measure |
Fluconazole
n=4 Participants
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).
Fluconazole: 400mg orally once daily (Day 1-14)
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
|
Placebo
n=4 Participants
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).
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Fluconazole placebo: Once daily
|
|---|---|---|
|
The Change in High-sensitivity C-reactive Protein (hsCRP)
|
4.1 mg/dL
Interval 1.1 to 8.3
|
-2 mg/dL
Interval -2.9 to 1.6
|
SECONDARY outcome
Timeframe: 105 daysNumber of Medication Side Effects and/or Adverse Events (AEs)
Outcome measures
| Measure |
Fluconazole
n=4 Participants
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).
Fluconazole: 400mg orally once daily (Day 1-14)
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
|
Placebo
n=4 Participants
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).
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Fluconazole placebo: Once daily
|
|---|---|---|
|
Safety and Tolerability of the Treatment Regimen Based on Medication Side Effects and/or Adverse Events (AEs).
|
31 Events
|
12 Events
|
Adverse Events
Fluconazole
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Fluconazole
n=4 participants at risk
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).
Fluconazole: 400mg orally once daily (Day 1-14)
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
|
Placebo
n=4 participants at risk
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).
Vancomycin: 500mg oral suspension 4 times daily (Day 1-14)
Neomycin: neomycin 1000 mg orally three times daily (Days 1-3)
Ciprofloxacin: ciprofloxacin 750 mg orally twice daily (Day 4-14)
Polyethylene Glycol 3350: 238 g dissolved in 64 ounces of Gatorade or Crystal Lite on day 2
Promethazine: PRN (as needed) Promethazine 12.5mg up to every four hours (Days 1-3).
Fluconazole placebo: Once daily
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
100.0%
4/4 • Number of events 4 • 105 days
|
50.0%
2/4 • Number of events 2 • 105 days
|
|
Gastrointestinal disorders
Vomiting
|
25.0%
1/4 • Number of events 1 • 105 days
|
0.00%
0/4 • 105 days
|
|
Gastrointestinal disorders
Increased abdominal pain
|
75.0%
3/4 • Number of events 3 • 105 days
|
0.00%
0/4 • 105 days
|
|
Gastrointestinal disorders
Increased diarrhea
|
75.0%
3/4 • Number of events 3 • 105 days
|
75.0%
3/4 • Number of events 3 • 105 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
25.0%
1/4 • Number of events 1 • 105 days
|
0.00%
0/4 • 105 days
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/4 • 105 days
|
25.0%
1/4 • Number of events 1 • 105 days
|
|
Gastrointestinal disorders
Perianal irritation
|
0.00%
0/4 • 105 days
|
25.0%
1/4 • Number of events 1 • 105 days
|
|
Skin and subcutaneous tissue disorders
Flushing
|
25.0%
1/4 • Number of events 1 • 105 days
|
0.00%
0/4 • 105 days
|
|
Gastrointestinal disorders
Decreased appetite
|
25.0%
1/4 • Number of events 1 • 105 days
|
0.00%
0/4 • 105 days
|
|
Eye disorders
Eye irritation
|
0.00%
0/4 • 105 days
|
25.0%
1/4 • Number of events 1 • 105 days
|
|
Gastrointestinal disorders
Defecation urgency
|
0.00%
0/4 • 105 days
|
25.0%
1/4 • Number of events 1 • 105 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place