Crohn's DiseasePhase 4EENCDNCT03833596
Exclusive Enteral Nutrition and Corticosteroids Therapy in Crohn's Disease (EENCD)
A Phase 4 study testing Prednisone and Exclusive Enteral Nutrition in people with Crohn's Disease, run by McMaster University at 1 site in Canada.
Trial summary
This study evaluates the effect of Exclusive Enteral Nutrition (EEN) in addition to different regimes of corticosteroid (CS) therapy (Prednisone) compared to CS alone in adults participants with active Crohn's Disease, on symptoms and inflammation after 6 weeks of treatment. 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?
- Prednisone and Exclusive Enteral Nutrition
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteCanada
- Study dates
- 25 Oct 2018to 1 Nov 2019
- Phase
- Phase 4
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed CD for at least 6 months
- Clinically active disease (CDAI >220 or Harvey-Bradshaw Index (HBI) >6) or active by endoscopy.
- Biochemical evidence of disease activity (CRP >5 and/or fecal calprotectin >250)
Who cannot join
- Currently using EEN
- Condition that would preclude the use of EEN, such as Intestinal obstruction, perforation, toxic megacolon, massive gastrointestinal bleeding, abdominal abscess, or stricturing disease
- Previous intestinal resection with a remnant bowel of less than 180 cm
- Treatment with Prednisone in the last 30 days
- New start or change in dose of azathioprine, 6-mercaptopurine, cyclosporine, other immunosuppressant or biologics in the last 90 days. Doses of these medications must also remain unchanged for the duration of the study
- New start or change in dose of 5-aminosalicylic acid (ASA) in the last 30 days. 5ASA dose must remain unchanged for the duration of the study
Show all 9Show fewer
- Use of Antibiotics or Probiotics in the last 30 days
- Pregnant or Lactating
- Any serious illness which could interfere with study procedures or results
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Synergistic Effect of Exclusive Enteral Nutrition Formula in Addition to Corticosteroids Therapy to Induce Clinical Remission in Patients With Crohn's Disease: a Pilot Study Involving a Multidimensional Assessment of Potential Mechanisms
This study evaluates the effect of Exclusive Enteral Nutrition (EEN) in addition to different regimes of corticosteroid (CS) therapy (Prednisone) compared to CS alone in adults participants with active Crohn's Disease, on symptoms and inflammation after 6 weeks of treatment. Participants will be randomized to three treatment arms: standard CS, standard CS with EEN, short course CS with EEN. Participants will be assessed through questionnaires for gut symptoms, quality of life, mood changes and dietary patterns and potential mechanisms will be investigated by collecting stool samples for characterization of gut bacterial profiles, collection of blood to determine inflammatory markers and evaluation of gut motility before and after treatment. The investigators hypothesize that six weeks of EEN with CS will be more effective than CS alone in inducing clinical remission in patients with active CD, as well as leading to beneficial changes in the composition and/or metabolic activity of the intestinal microbiota, gastrointestinal transit and inflammatory burden. Furthermore, six weeks of EEN in addition to a short course of CS will have similar efficacy than EEN with standard course of CS and reduced number of adverse events.
Read the detailed description
Crohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by diarrhea, abdominal pain and bleeding. There are several treatment options but the most-widely used for acute therapy are corticosteroids (CS), however, CS are often associated with severe side effects. The administration of a formula for exclusive feeding (EEN) is well-established as an alternative to CS in children with Crohn's disease (CD). EEN has been proposed to reduce inflammation in the gut. However, this intervention is not routinely used in adults, in part because of uncertainty regarding the magnitude of the benefit of EEN reported in previous studies. Although few studies have examined the effects of EEN in adult patients with active CD, the potentially synergistic effects of adding EEN to the conventional CS was not explored. Furthermore, it is also possible that the addition of EEN allows to decrease the duration of CS therapy; however, this was not investigated before.
The investigators propose that an oral formula may help decrease gut inflammation and improve nutritional status through modulation of gut bacteria. The investigators will therefore evaluate the effect of exclusive formula feeding therapy in addition to different regimes of CS therapy compared to CS alone in adult patients with active CD, on symptoms and inflammation after 6 weeks of treatment. Participants will be randomized to three treatment arms: standard CS, standard CS with EEN, short course CS with EEN. The investigators will collect information through questionnaires that assess gut symptoms, quality of life, mood changes and dietary patterns. To investigate potential mechanisms, the investigators will collect stool samples to characterize gut bacterial profiles, blood to determine inflammatory markers and evaluate gut movements (motility) before, and after the treatment. The investigators hope that the results will lead to better understanding of the beneficial effect of exclusive formula feeding in addition to CS as a more efficacious alternative than CS alone, and to understand the mechanisms of this therapy.
- Conditions
- Crohn's Disease
- Being tested
- Prednisone, Exclusive Enteral Nutrition
- Keywords
- Corticosteroids, Exclusive Enteral Nutrition
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoneDrug
All 3 arms will receive Prednisone - 2 will be standard course treatment, 1 will be short course and rapidly-tapered
Exclusive Enteral NutritionDietary supplement
Also called Modulen (Nestlé)
2 arms will receive EEN, in concurrence with either regular-course or short course and rapidly-tapered CS.
| Study group | Role | What they receive |
|---|---|---|
| Standard course CS with Regular Food | Active comparator | 40 mg a day of oral Prednisone for 2 weeks with subsequent taper of daily dose by 5 mg per week. Receives: Drug: Prednisone |
| Standard course CS with EEN | Experimental | 40 mg a day of oral Prednisone for 2 weeks and taper of daily dose by 5 mg per week and Exclusive Enteral Nutrition for 6 weeks. Receives: Drug: Prednisone; Dietary Supplement: Exclusive Enteral Nutrition |
| Short course CS with EEN | Experimental | 40 mg a day of oral Prednisone for 3 days and taper of daily dose by 5 mg every 3 days and Exclusive Enteral Nutrition for 6 weeks. Receives: Drug: Prednisone; Dietary Supplement: Exclusive Enteral Nutrition |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of 6 weeks of EEN and CS in inducing remission (Crohn's Disease Activity Index - CDAI<150) in adult patients with active CD (CDAI>220 and either CRP>5 or fecal calprotectin >250mg/l)
Assess the efficacy of 6 weeks of EEN and CS in inducing remission (Crohn's Disease Activity Index (CDAI)<150) compared to treatment with CS alone in adult patients with active CD (CDAI>220 and either CRP>5 or fecal calprotectin >250mg/l)
Measured: 2 years
Secondary outcomes (9)
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing clinical disease improvement
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing clinical disease improvement (drop in Crohns Disease Activity Index - CDAI>70)
Measured: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in improving quality of life
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in improving quality of life (Short Inflammatory Bowel Disease Questionnaire (SIBDQ)) Total score ranges from 10 to 70 (higher values indicate better outcome). Subscales are divided into systemic (score range 2 to 14), social (score range 2 to 14), bowel (score range 3 to 21) and emotional (score range 3 to 21)
Measured: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing biochemical remission
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing biochemical remission (normalization of either serum CRP (CRP<5) and/or fecal calprotectin (less than 250mg/l)
Measured: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in normalizing colonic transit
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in normalizing colonic transit (SHAPE) among those with altered transit at baseline. Participants will take one capsule containing 24 markers and have an X-Ray done on day 5. If >20% markers (6 markers or more) are retained it is considered delayed transit.
Measured: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing anxiety and/or depression scores
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing anxiety and/or depression scores (decrease >2 points in Hospital Anxiety and Depression Scale. Total score ranges from 0 to 42, lower values indicating better outcome. Subscale HAD-A (anxiety) and HAD-D (depression) range from 0 to 21.
Measured: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in increasing body weight and improving nutritional status
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in increasing body weight and improving nutritional status (increased levels of micronutrients: vitamin A, vitamin B12, 25-hydroxy vitamin D, chromium, copper and zinc)
Measured: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing number of adverse events
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing number of adverse events
Measured: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing changes in microbiota composition
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing changes in microbiota composition (change in alpha diversity by 16S sequencing Illumina)
Measured: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing indirect markers of mucosal integrity
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing indirect markers of mucosal integrity (IFABP2)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2019
- Study start25 Oct 2018
- Primary completion1 Nov 2019
- Study completion1 Nov 2019
Why it stopped: Low recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized control trial with three arms of treatment: EEN plus standard or short course of CS versus CS alone.
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Société des Produits Nestlé (SPN)
- Responsible party
- Principal investigator, Maria Ines Pinto Sanchez, McMaster University
- Investigators
- Maria I Pinto-Sanchez, MD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03833596
- Sponsor's protocol ID
- EEN in Crohn
- Acronym
- EENCD
- Status last verified
- Feb 2019
- First submitted
- 21 Dec 2018
- Last updated
- 2 Sep 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Synergistic Effect of Exclusive Enteral Nutrition Formula in Addition to Corticosteroids Therapy to Induce Clinical Remission in Patients With Crohn's Disease: a Pilot Study Involving a Multidimensional Assessment of Potential Mechanisms
- ClinicalTrials.gov ID
- NCT03833596
- Acronym / sponsor ID
- EENCD / EEN in Crohn
- Conditions
- Crohn's Disease
- Keywords
- Corticosteroids, Exclusive Enteral Nutrition
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Société des Produits Nestlé (SPN)
- Study start
- 25 Oct 2018 (actual)
- Primary completion
- 1 Nov 2019 (actual)
- Study completion
- 1 Nov 2019 (actual)
- First posted
- 7 Feb 2019 (actual)
- 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.
This study evaluates the effect of Exclusive Enteral Nutrition (EEN) in addition to different regimes of corticosteroid (CS) therapy (Prednisone) compared to CS alone in adults participants with active Crohn's Disease, on symptoms and inflammation after 6 weeks of treatment. Participants will be randomized to three treatment arms: standard CS, standard CS with EEN, short course CS with EEN. Participants will be assessed through questionnaires for gut symptoms, quality of life, mood changes and dietary patterns and potential mechanisms will be investigated by collecting stool samples for characterization of gut bacterial profiles, collection of blood to determine inflammatory markers and evaluation of gut motility before and after treatment. The investigators hypothesize that six weeks of EEN with CS will be more effective than CS alone in inducing clinical remission in patients with active CD, as well as leading to beneficial changes in the composition and/or metabolic activity of the intestinal microbiota, gastrointestinal transit and inflammatory burden. Furthermore, six weeks of EEN in addition to a short course of CS will have similar efficacy than EEN with standard course of CS and reduced number of adverse events.
Detailed description
Crohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by diarrhea, abdominal pain and bleeding. There are several treatment options but the most-widely used for acute therapy are corticosteroids (CS), however, CS are often associated with severe side effects. The administration of a formula for exclusive feeding (EEN) is well-established as an alternative to CS in children with Crohn's disease (CD). EEN has been proposed to reduce inflammation in the gut. However, this intervention is not routinely used in adults, in part because of uncertainty regarding the magnitude of the benefit of EEN reported in previous studies. Although few studies have examined the effects of EEN in adult patients with active CD, the potentially synergistic effects of adding EEN to the conventional CS was not explored. Furthermore, it is also possible that the addition of EEN allows to decrease the duration of CS therapy; however, this was not investigated before.
The investigators propose that an oral formula may help decrease gut inflammation and improve nutritional status through modulation of gut bacteria. The investigators will therefore evaluate the effect of exclusive formula feeding therapy in addition to different regimes of CS therapy compared to CS alone in adult patients with active CD, on symptoms and inflammation after 6 weeks of treatment. Participants will be randomized to three treatment arms: standard CS, standard CS with EEN, short course CS with EEN. The investigators will collect information through questionnaires that assess gut symptoms, quality of life, mood changes and dietary patterns. To investigate potential mechanisms, the investigators will collect stool samples to characterize gut bacterial profiles, blood to determine inflammatory markers and evaluate gut movements (motility) before, and after the treatment. The investigators hope that the results will lead to better understanding of the beneficial effect of exclusive formula feeding in addition to CS as a more efficacious alternative than CS alone, and to understand the mechanisms of this therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Randomized control trial with three arms of treatment: EEN plus standard or short course of CS versus CS alone.
| Arm | Type | Receives |
|---|---|---|
| Standard course CS with Regular Food | Active comparator | Drug: Prednisone40 mg a day of oral Prednisone for 2 weeks with subsequent taper of daily dose by 5 mg per week. |
| Standard course CS with EEN | Experimental | Drug: Prednisone, Dietary Supplement: Exclusive Enteral Nutrition40 mg a day of oral Prednisone for 2 weeks and taper of daily dose by 5 mg per week and Exclusive Enteral Nutrition for 6 weeks. |
| Short course CS with EEN | Experimental | Drug: Prednisone, Dietary Supplement: Exclusive Enteral Nutrition40 mg a day of oral Prednisone for 3 days and taper of daily dose by 5 mg every 3 days and Exclusive Enteral Nutrition for 6 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Confirmed CD for at least 6 months
- Clinically active disease (CDAI >220 or Harvey-Bradshaw Index (HBI) >6) or active by endoscopy.
- Biochemical evidence of disease activity (CRP >5 and/or fecal calprotectin >250)
Key exclusion criteria (9 listed)
- Currently using EEN
- Condition that would preclude the use of EEN, such as Intestinal obstruction, perforation, toxic megacolon, massive gastrointestinal bleeding, abdominal abscess, or stricturing disease
- Previous intestinal resection with a remnant bowel of less than 180 cm
- Treatment with Prednisone in the last 30 days
- New start or change in dose of azathioprine, 6-mercaptopurine, cyclosporine, other immunosuppressant or biologics in the last 90 days. Doses of these medications must also remain unchanged for the duration of the study
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 |
|---|---|---|
| PrednisoneAll 3 arms will receive Prednisone - 2 will be standard course treatment, 1 will be short course and rapidly-tapered | Drug | Short course CS with EEN, Standard course CS with EEN, Standard course CS with Regular Food |
| Exclusive Enteral NutritionAlso: Modulen (Nestlé)2 arms will receive EEN, in concurrence with either regular-course or short course and rapidly-tapered CS. | Dietary supplement | Short course CS with EEN, Standard course CS with EEN |
Primary outcome
Efficacy of 6 weeks of EEN and CS in inducing remission (Crohn's Disease Activity Index - CDAI<150) in adult patients with active CD (CDAI>220 and either CRP>5 or fecal calprotectin >250mg/l)
Time frame: 2 years
Assess the efficacy of 6 weeks of EEN and CS in inducing remission (Crohn's Disease Activity Index (CDAI)<150) compared to treatment with CS alone in adult patients with active CD (CDAI>220 and either CRP>5 or fecal calprotectin >250mg/l)
9 secondary outcomes
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing clinical disease improvement
Time frame: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in improving quality of life
Time frame: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing biochemical remission
Time frame: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in normalizing colonic transit
Time frame: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing anxiety and/or depression scores
Time frame: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in increasing body weight and improving nutritional status
Time frame: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing number of adverse events
Time frame: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in inducing changes in microbiota composition
Time frame: 2 years
Determine the beneficial effect of 6 weeks of EEN and CS as compared to CS alone in decreasing indirect markers of mucosal integrity
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Low recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2020.
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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.
Maria I Pinto-Sanchez, MD principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Prednisone and Exclusive Enteral Nutrition in people with Crohn's Disease, run by McMaster University at 1 site in Canada.
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 3 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 2 Sep 2020. 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 Canada. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Low recruitment). 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?
Efficacy of 6 weeks of EEN and CS in inducing remission (Crohn's Disease Activity Index - CDAI<150) in adult patients with active CD (CDAI>220 and either CRP>5 or fecal calprotectin >250mg/l) (time frame: 2 years). 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 2 Sep 2020.