Ulcerative Colitis (UC)NCT02217722
Use of the Ulcerative Colitis Diet for Induction of Remission
A study testing Ulcerative Colitis Diet and Antibiotic cocktail in people with Ulcerative Colitis (UC), run by Prof. Arie Levine at 1 site in Israel.
Trial summary
The goal of the study is to evaluate the use of Ulcerative Colitis Diet for Induction of Remission. The investigators have postulated that we developed could be beneficial for patients with Ulcerative Colitis. To date, no study has explored this possibility. Read more about this study
- Who is it for?
- Ages 5 to 18 years
- Conditions the study is for
- Ulcerative Colitis (UC)
- What is being tested?
- Ulcerative Colitis Diet and Antibiotic cocktail
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteIsrael
- Study dates
- Oct 2014to Feb 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 5 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Informed consent
- Established diagnosis of UC disease.
- Age: 5 - 18 years ( inclusive)
- Mild to moderate active disease, 10 ≤ PUCAI ≤45.
- Stable medication (IMM/ 5ASA) use for the past 6 weeks.
- For patients who received antibiotic treatment: age 10-18 (inclusive).
Who cannot join
- Any proven infection such as positive stool culture, parasite or C.difficile.
- Use of Antibiotics
- Use of steroids in the previous two weeks only
- Patients that are refractory to full dose steroids ( 1 mg/kg/day)
- Past acute severe UC.
- Current Extra intestinal manifestation of UC.
Show all 9Show fewer
- Pregnancy.
- A subset of patients who are on steroids and relapse during steroids treatment ≤0.5 mg/kg with mild to moderate disease activity will act as a second subset for this exploratory study.
- -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open Label Non Randomized Pilot Study: Use of the Ulcerative Colitis Diet for Induction of Remission.
The goal of the study is to evaluate the use of Ulcerative Colitis Diet for Induction of Remission. The investigators have postulated that we developed could be beneficial for patients with Ulcerative Colitis. To date, no study has explored this possibility.
Read the detailed description
Background:
Recent research has shown that dietary components may lead to impaired intestinal innate immunity due to alterations in the microbiome, mucous layer, intestinal permeability or change in bacterial adherence and translocation. Pfeffer Gik et al (Dig Dis, 2014) compiled a list of food components and additives that impair the intestinal epitheliums ability to contain bacteria to the lumen, and consequently increase intestinal permeability which, in turn, increases the uptake of luminal antigens and microbial factors. The list includes Gliadin, Saturated fat milks, emulsifiers such as Carboxymethylcellulose, Polysorbate 80 and Sodium Caprate )Levine A, Wine E, 2013). In Crohn's disease, intervention with EEN or a Crohn's disease exclusion diet have shown high rates of remission in mild- moderate CD patients. The CDED led to remission in 70% of patients, primarily with patients with early mild to moderate disease (Sigall-Boneh R et al, 2014).
Unlike CD, none of these studies have systematically examined the relationship between normal diet intake and relapses in UC. Devotka et al demonstrated that a bloom in sulphide reducing bacteria increased colitis in IL10-/- mice. This was due to increased Bilophila Wadsworthia which is sulphide dependent (Brown k et al, 2012). Studies have shown that the rate of butyrate utilization in normal specimens was almost double than that found in UC Specimens. Moreover, high fiber diet can affect the microbial composition (Pitcher MCL et al, Gut, 2000) and regulatory T cells in the colon (Singh N et al, 2014).
Until recently, UC was not considered to be a bacteria mediated disease. However, our increased understanding of UC indicates that bacteria might have a role in pathogenesis or severity of the disease. The strongest evidence comes from Japanese studies in patients with moderate to severe colitis, which demonstrated that triple therapy with penicillin , tetracycline and metronidazole led to remission in steroid refractory patients in 60% of patients, and this was reproduced in a follow up randomized controlled trial which showed a 70% remission rate (UEGW Amsterdam 2012, Ohkusa T et al 2005 ). On the other hand a previous trial had shown 44% response and only (Ohkusa T et al 2010). A recent retrospective study in Israel showed a 65% response and 50% remission rate in patients with severe refractory colitis. Thus it is unclear at present if antibiotics are useful only in severe colitis , or if this reflects heterogeneity among studies.
Diet and antibiotics are the two proven treatments that may alter the microbiota clinically. Theoretically, controlling the microbiota by diet or antibiotics may allow for control of the disease without immune suppression , and this has yet to be evaluated.
Based on our previous success in improving remission and decreasing inflammation with a novel dietary intervention in Crohn's disease, and based on these previously mentioned studies, we have postulated that a diet could be beneficial for patients with Ulcerative Colitis. We further hypothesize that patients failing diet might respond to antibiotic therapy If patients respond to the diet this would have an immediate impact and be the first evidence for a specific diet that works in UC. If the diet fails and the antibiotics succeed, this would be the first evidence for the effect of oral antibiotics in mild disease .
- Conditions
- Ulcerative Colitis (UC)
- Being tested
- Ulcerative Colitis Diet, Antibiotic cocktail
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ulcerative Colitis DietOther
we have postulated that a diet that increases butyrate through fiber exposure, reduces intestinal sulfur exposure, and increases vitamin D levels could be beneficial for patients with Ulcerative Colitis. To date, no study has explored this possibility.
Antibiotic cocktailDrug
Also called Doxycyclin, amoxicillin and metronidazole
We have postulating that antibiotic therapy can alter the microbiota clinically. Controlling the microbiota by antibiotics may allow for control of the disease without immune suppression
| Study group | Role | What they receive |
|---|---|---|
| Ulcerative Colitis Diet counseling | Experimental | Patients will receive a structured novel diet termed the UCD for 6 weeks. . patients that completed induction phase with remission(PUCAI<10) will be asked if they are willing to adhere to the UCD for an additional 20 weeks. Receives: Other: Ulcerative Colitis Diet |
| Antibiotic Treatment | Experimental | Patients failing to enter or maintain remission by 6 weeks, or with worsening disease at any time after week 2 will be considered failures on an intention to treat basis. Eligible patients at this time at aged 10 or above may receive a 14 day antibiotic course with Doxycycline, amoxicillin and metronidazole.In addition to the description above children who refused to UCD or with low adherence to UCD may be enrolled directly to this arm. Receives: Drug: Antibiotic cocktail |
What is being measured
The primary outcome is the main question the study is designed to answer.
Remission rate, defined as a PUCAI less than 10 at week 6.
Measured: week 6
Secondary outcomes (2)
Change in Mean PUCAI week 6.
Measured: week 6
Change in mean Calprotectin week 6
Measured: week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2014 (estimated)
- Study startOct 2014
- Primary completionDec 2015
- Study completionFeb 2016
Why it stopped: We have submitted a multi center study, with the same nutritional therapy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative Colitis (UC)Studies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prof. Arie Levine
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Prof. Arie Levine, Wolfson Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02217722
- Sponsor's protocol ID
- 0096-14-WOMC
- Status last verified
- Aug 2016
- First submitted
- 20 Jul 2014
- Last updated
- 11 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Non Randomized Pilot Study: Use of the Ulcerative Colitis Diet for Induction of Remission.
- ClinicalTrials.gov ID
- NCT02217722
- Acronym / sponsor ID
- 0096-14-WOMC
- Conditions
- Ulcerative Colitis (UC)
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: We have submitted a multi center study, with the same nutritional therapy
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Prof. Arie LevineOther government
- Study start
- Oct 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 15 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of the study is to evaluate the use of Ulcerative Colitis Diet for Induction of Remission. The investigators have postulated that we developed could be beneficial for patients with Ulcerative Colitis. To date, no study has explored this possibility.
Detailed description
Background:
Recent research has shown that dietary components may lead to impaired intestinal innate immunity due to alterations in the microbiome, mucous layer, intestinal permeability or change in bacterial adherence and translocation. Pfeffer Gik et al (Dig Dis, 2014) compiled a list of food components and additives that impair the intestinal epitheliums ability to contain bacteria to the lumen, and consequently increase intestinal permeability which, in turn, increases the uptake of luminal antigens and microbial factors. The list includes Gliadin, Saturated fat milks, emulsifiers such as Carboxymethylcellulose, Polysorbate 80 and Sodium Caprate )Levine A, Wine E, 2013). In Crohn's disease, intervention with EEN or a Crohn's disease exclusion diet have shown high rates of remission in mild- moderate CD patients. The CDED led to remission in 70% of patients, primarily with patients with early mild to moderate disease (Sigall-Boneh R et al, 2014).
Unlike CD, none of these studies have systematically examined the relationship between normal diet intake and relapses in UC. Devotka et al demonstrated that a bloom in sulphide reducing bacteria increased colitis in IL10-/- mice. This was due to increased Bilophila Wadsworthia which is sulphide dependent (Brown k et al, 2012). Studies have shown that the rate of butyrate utilization in normal specimens was almost double than that found in UC Specimens. Moreover, high fiber diet can affect the microbial composition (Pitcher MCL et al, Gut, 2000) and regulatory T cells in the colon (Singh N et al, 2014).
Until recently, UC was not considered to be a bacteria mediated disease. However, our increased understanding of UC indicates that bacteria might have a role in pathogenesis or severity of the disease. The strongest evidence comes from Japanese studies in patients with moderate to severe colitis, which demonstrated that triple therapy with penicillin , tetracycline and metronidazole led to remission in steroid refractory patients in 60% of patients, and this was reproduced in a follow up randomized controlled trial which showed a 70% remission rate (UEGW Amsterdam 2012, Ohkusa T et al 2005 ). On the other hand a previous trial had shown 44% response and only (Ohkusa T et al 2010). A recent retrospective study in Israel showed a 65% response and 50% remission rate in patients with severe refractory colitis. Thus it is unclear at present if antibiotics are useful only in severe colitis , or if this reflects heterogeneity among studies.
Diet and antibiotics are the two proven treatments that may alter the microbiota clinically. Theoretically, controlling the microbiota by diet or antibiotics may allow for control of the disease without immune suppression , and this has yet to be evaluated.
Based on our previous success in improving remission and decreasing inflammation with a novel dietary intervention in Crohn's disease, and based on these previously mentioned studies, we have postulated that a diet could be beneficial for patients with Ulcerative Colitis. We further hypothesize that patients failing diet might respond to antibiotic therapy If patients respond to the diet this would have an immediate impact and be the first evidence for a specific diet that works in UC. If the diet fails and the antibiotics succeed, this would be the first evidence for the effect of oral antibiotics in mild disease .
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ulcerative Colitis Diet counseling | Experimental | Other: Ulcerative Colitis DietPatients will receive a structured novel diet termed the UCD for 6 weeks. . patients that completed induction phase with remission(PUCAI<10) will be asked if they are willing to adhere to the UCD for an additional 20 weeks. |
| Antibiotic Treatment | Experimental | Drug: Antibiotic cocktailPatients failing to enter or maintain remission by 6 weeks, or with worsening disease at any time after week 2 will be considered failures on an intention to treat basis. Eligible patients at this time at aged 10 or above may receive a 14 day antibiotic course with Doxycycline, amoxicillin and metronidazole.In addition to the description above children who refused to UCD or with low adherence to UCD may be enrolled directly to this arm. |
Who may qualify
- Ages
- 5 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Informed consent
- Established diagnosis of UC disease.
- Age: 5 - 18 years ( inclusive)
- Mild to moderate active disease, 10 ≤ PUCAI ≤45.
- Stable medication (IMM/ 5ASA) use for the past 6 weeks.
Key exclusion criteria (9 listed)
- Any proven infection such as positive stool culture, parasite or C.difficile.
- Use of Antibiotics
- Use of steroids in the previous two weeks only
- Patients that are refractory to full dose steroids ( 1 mg/kg/day)
- Past acute severe UC.
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 |
|---|---|---|
| Ulcerative Colitis Dietwe have postulated that a diet that increases butyrate through fiber exposure, reduces intestinal sulfur exposure, and increases vitamin D levels could be beneficial for patients with Ulcerative Colitis. To date, no study has explored this possibility. | Other | Ulcerative Colitis Diet counseling |
| Antibiotic cocktailAlso: Doxycyclin, amoxicillin and metronidazoleWe have postulating that antibiotic therapy can alter the microbiota clinically. Controlling the microbiota by antibiotics may allow for control of the disease without immune suppression | Drug | Antibiotic Treatment |
Primary outcome
Remission rate, defined as a PUCAI less than 10 at week 6.
Time frame: week 6
2 secondary outcomes
Change in Mean PUCAI week 6.
Time frame: week 6
Change in mean Calprotectin week 6
Time frame: week 6
Results and safety
The study was stopped early (reason given: We have submitted a multi center study, with the same nutritional therapy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2016.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ulcerative Colitis Diet and Antibiotic cocktail in people with Ulcerative Colitis (UC), run by Prof. Arie Levine at 1 site in Israel.
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 6 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: stopped early, as of the sponsor's last update on 11 Aug 2016. 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 Israel. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: We have submitted a multi center study, with the same nutritional therapy). Results are not available in the source record.
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?
Remission rate, defined as a PUCAI less than 10 at week 6. (time frame: week 6). 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 11 Aug 2016.