Prospective Dietary Therapy Using Crohn's Disease Exclusion Diet for Ileal Pouch Anal Anastomosis Patients

Pouchitis Clinical Trial

Official title:

Prospective Dietary Therapy Using Crohn's Disease Exclusion Diet ("CDED") for Ileal Pouch Anal Anastomosis ("IPAA") Patients With Endoscopic Deterioration or Clinically Suspected Pouchitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04327219
• Other study ID #: TASMC-0637-19-CTIL
• Status: Recruiting
• Phase: N/A
• Start date: April 1, 2020
• Est. completion date: April 1, 2023

Study information

• Verified date: January 2022
• Source: Tel-Aviv Sourasky Medical Center
• Contact: Nitsan Maharshak, Dr.
• Phone: +972527360384
• Email: nitsanm[@]tlvmc.gov.il
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with ulcerative colitis (UC) who require surgery. Inflammation of the ileal pouch (pouchitis) occurs in up to 60% of pouch patients.

Although, pouchitis patients are former UC patients, the disease occurs in the small intestine, similarly to Crohn's disease (CD). Further, the disease can be clinically similar to CD, involving the proximal gastro-intestinal tract and causing strictures, fistula, or perianal disease.

The Crohn's Disease Exclusion Diet (CDED) reduces exposure to all the components identified in rodent models as well as two components that are highly suspect but have not been investigated in models. The diet also provides dietary components that may favor species (especially SCFA producers) which appear to be deficient in CD.

The investigator therefore aims to examine the microbial, mucosal and immunological changes of the pouch during one year post IPAA, and examine the impact of the CDED on disease activity and dysbiosis in a cohort of adults suffering from active pouchitis.

Description:

Hypothesis (es) and Aims:

1. The investigator aims to evaluate the natural development of the pouch microenvironment among post-IPAA patients over one year of follow-up, and associate dietary intake with shaping the pouch microbiome composition, metabolic activity, proteolytic activity and with development of pouchitis.

The investigator hypothesizes that the different dietary pattern of post-IPAA patients will be associated with different pouch microenvironments, and with the development of pouchitis.

2. The investigator aims to measure the effect of the CDED on shaping the pouch microenvironment among post-IPAA patients over one year of follow-up, compared with a control standard diet. The investigator further aims to assess if the CDED is an effective mean of prevention of pouchitis in post-IPAA patients.

The investigator hypothesizes that adherence to the CDED post-IPAA will positively effect the pouch microbiome composition, metabolic activity and proteolytic activity, and be an efficient means to maintain surgical remission in pouch patients, compared with a control standard diet.

3. The investigator aims to evaluate the effect of the CDED on acute pouchitis activity compared with a control-standard diet.

The investigator hypothesizes that the CDED will induce clinical, biological and endoscopic remission in pouchitis patients, and that remission will be maintained through 24 weeks. Results are expected to show superiority over a standard diet for clinical remission in pouchitis patients.

4. The investigator aims to examine whether changes in circadian rhythm are associated with improvement in clinical and biological disease activity.

Study plan:

1. POST IPAA SURGERY PATIENTS:

1.1 Twenty patients, at 0-3 months post ileostomy closure will be enrolled for the study. Patients will be randomized to receive the CDED or standard diet at a ratio of 1:1. Patients will undergo 5 clinic visits for dietary education and guidance at baseline, weeks 3, 6, 12 and 24 in which they would be closely monitored for dietary adherence, physician assessment of disease ativity, patient reported outcomes (PROMS) and quality of life. Patient followup under the CDED maintenance phase, including data collection will continue every 8 weeks up to 52 weeks.

1.2 Pouchoscopy will be performed at baseline (unless preformed within 2 months of inclusion), week 12, week 24 and week 52, to assess pouchitis activity and to retrieve mucosal samples for histology, mucosal adherent bacteria assessment, and RNA extraction 1.3 Screening: At baseline, inclusion and exclusion criteria will be evaluated, informed consent obtained and participants asked to provide stool, urine and blood samples, undergo anthropometric evaluation, and fill in lifestyle, quality of life and nutritional questionnaires.

Baseline pouchoscopy will include validation of endoscopic inclusion criteria and sampling of intestinal tissue.

Patients will be randomized to undergo the CDED or receive a standard diet personally tailored for patient's nutritional needs and symptoms by a trained dietitian.

1.4 Follow-up Patients will be evaluated for a disease activity index (mPDAI), CBC, CRP, calprotectin, albumin and weight at each of the visits (baseline, week 3, week 6, week 12, week 24 and week 52). Biological samples will be analyzed and preserved for future analysis at -80 at each visit.

Dietary compliance will be assessed by a modified MARS questionnaire at each visit and by dieticians using a 3 days food diary at four time points (week 3 , 6, 12 and 24), and two telephone calls one week after each change at weeks 1 and 7.

All patients will undergo a pouchoscopy at the end of 12 and 24 weeks of the diet for evaluation of disease activity and tissue sample collection.

After week 24, patients who do not respond to treatment at either arm, will be defined as treatment failures. Those who do respond and who achieve steroid free clinical remission, will be instructed to continue with the maintenance diet until week 52 of the study followup.

2. study plan: 2.1 Fourty two adults with a diagnosis of acute exacerbation of pouchitis will be included in the study. Participants will be randomized to receive the CDED or standard diet at a ratio of 1:1. Patients will undergo 5 clinic visits for dietary education and guidance at baseline, weeks 3, 6, 12 ans 24 in which they would be closely monitored for dietary adherence, physician assessment of disease activity, patient reported outcomes (PROMS) and quality of life.

After 6 weeks of CDED phase 1, patients will be clinically evaluated to define clinical response as reduction in clinical PDAI>1 point. Patients receiving the standard diet who do not achieve clinical remission at week 6 will be able to be re-allocated to the CDED arm per protocol. Patients who do achieve remission will continue with their tailored diet until week 24.

Pouchoscopy will be performed at baseline (unless preformed within 2 months of inclusion), week 12 and week 24 to assess pouchitis activity and to retrieve mucosal samples for histology, mucosal adherent bacteria assessment, and RNA extraction 2.2 Follow-up: Patients will be evaluated for a disease activity index (mPDAI), CBC, CRP, calprotectin, albumin and weight at each of 5 visits (baseline, week 3, week 6, week 12, and week 24). Biological samples will be analyzed and preserved for future analysis at -80 at each visit.

Dietary compliance will be assessed by a modified MARS questionnaire at each visit and by dieticians using a 3 days food diary at four time points (week 3 , 6, 12 and 24), and two telephone calls one week after each change at weeks 1 and 7.

All patients will undergo a pouchoscopy at the end of 12 and 24 weeks of the diet for evaluation of disease activity and tissue sample collection.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: April 1, 2023
• Est. primary completion date: April 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Post-IPAA for ulcerative colitis =3 months post-opp OR post -IPAA for UC 1.1 Active pouchitis defined as: 1.1.1 =5 points modified Pouch disease activity index (mPDAI), and one of the following: 1.1.2 Pouchoscopy demonstrating lesions in the ileum/jejunum/afferent pouch loop of the pouch, clinical PDAI>2 points 1.1.3 MR/CTEnterography with evidence of inflammation of the pouch 1.1.4 Fecal calprotectin>250 µg/gr

2. Lack of obstructive symptomes for 8 weeks

3. Stable medications and doses:

3.1 Immunomodulatory and biologics at least 8 weeks 3.2 Mesalamine at least 4 weeks 3.3 Medical cannabis at least 2 weeks 3.4 Budesonide dependent allowed if patients are active and budesonide dose is =6 mg, VIVOMIX probiotics allowed). Use of Antibiotics / Budesonide <6 mg at baseline*.

*Patients treated with steroids or antibiotics at baseline will be included in the study and be allowed to continue the study if they treated with a stable dose throughout at least 4 weeks. After 4 weeks if the trial, if they present clinical improvement, according to the judgment of the study physician, dose may be gradually reduced for the remaining trial without exclusion.

4. Informed consent and ability to complete the study protocol.

Exclusion Criteria:

1. Pregnancy

2. Use of systemic steroids / Budesonide >6 mg at baseline.

3. Currently active systemic diseases such as spondylo-arthropathies, collagen vascular disease, renal failure, hepatitis or heart disease

4. Positive Stool culture, stool parasites or clostridium difficile toxin or alternative C- Difficile test.

5. Evidence of bowel stricture

Related Conditions & MeSH terms

• Crhon's Disease Like of the Pouch
• Crohn Disease
• Pouchitis

Intervention

Other:
• CDED diet
examine the microbial, mucosal and immunological changes of the pouch during one year post IPAA, and examine the impact of the CDED on disease activity and dysbiosis in adults suffering from active pouchitis.

Locations

Country	Name	City	State
Israel	Dep. of Gastroenterology, Tel Aviv Sourasky Medical Center	Tel Aviv

Sponsors (1)

Lead Sponsor	Collaborator
Tel-Aviv Sourasky Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	steroid free clinical remission	defined as Clinical pouchitis disease activity index ("cPDAI" ranges between 0-6 where highest is the worst and lowest is best clinically) sub score=2 for pouchitis patients	week 6
Secondary	Steroid free clinical remission	defined as Clinical pouchitis disease activity index ("cPDAI" ranges between 0-6 where highest is the worst and lowest is best clinically) sub score=2	week 12
Secondary	Maintenance of clinical remission	defined as Clinical pouchitis disease activity index ("cPDAI" ranges between 0-6 where highest is the worst and lowest is best clinically) sub score=2	week 24
Secondary	clinical and endoscopic remission	defined as modified pouchitis disease activity index ("mPDAI" ranges between 0-12 where highest is the worst and lowest is best clinically) sub score<5	week 12
Secondary	clinical and endoscopic remission	defined as modified pouchitis disease activity index ("mPDAI" ranges between 0-12 where highest is the worst and lowest is best clinically) sub score<5	week 24
Secondary	Clinical response	reduction in Clinical pouchitis disease activity index ("cPDAI" ranges between 0-6 where highest is the worst and lowest is best clinically) =1	week 6
Secondary	Clinical response	reduction in Clinical pouchitis disease activity index ("cPDAI" ranges between 0-6 where highest is the worst and lowest is best clinically) =1	week 12
Secondary	Pouchitis remission	defined as pouchitis disease activity index ("PDAI" ranges between 0-18 where highest is the worst and lowest is best clinically) <7 points	week 12
Secondary	Pouchitis remission	defined as pouchitis disease activity index ("PDAI" ranges between 0-18 where highest is the worst and lowest is best clinically) <7 points	week 24
Secondary	Clinically significant change in mean CRP	normalization (CRP =5mg/l) of CRP or reduction in CRP of =10 mg/l	week 6
Secondary	Clinically significant change in mean CRP	normalization (CRP =5mg/l) of CRP or reduction in CRP of =10 mg/l	week 12
Secondary	Clinically significant change in mean CRP	normalization (CRP =5mg/l) of CRP or reduction in CRP of =10 mg/l	week 24
Secondary	Clinically significant change in mean fecal calprotectin	normalization (=150 mg/g) in calprotectin or reduction in calprotectin of =150mg/gr	week 6
Secondary	Clinically significant change in mean fecal calprotectin	normalization (=150 mg/g) in calprotectin or reduction in calprotectin of =150mg/gr	week 12
Secondary	Clinically significant change in mean fecal calprotectin	normalization (=150 mg/g) in calprotectin or reduction in calprotectin of =150mg/gr	week 24