Liquid Diets for Crohn's Disease

(mRE-EEN Trial)

Recruiting at 2 trial locations

Overseen By Danny Gagucas

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Seattle Children's Hospital

Must not be taking: Corticosteroids, Immunomodulators, Azathioprine, Methotrexate

Disqualifiers: Surgery, Perianal disease, Biologicals, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two different liquid diets for children recently diagnosed with Crohn's disease. One group will consume a regular formula, similar to infant or baby formula, while the other will prepare and drink a special smoothie using provided ingredients and a blender. Researchers aim to determine which diet is easier to adhere to and more effective at improving symptoms, gut health, and overall quality of life over 8 weeks. Suitable candidates for the trial are children diagnosed with Crohn's disease within the last two years who continue to experience symptoms. As an unphased trial, this study offers a unique opportunity to enhance understanding of dietary impacts on Crohn's disease in children.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have recently used corticosteroids, adjusted immunomodulators, or started certain medications like azathioprine or methotrexate close to the study's end. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both the whole-food blended smoothie and the commercial formula used in Exclusive Enteral Nutrition (EEN) for Crohn's disease are well-tolerated by patients. Studies have found that the whole-food smoothie is as effective and safe as the commercial formulas typically used in EEN. Patients experienced similar improvements in symptoms and reductions in FCP, a marker for inflammation, as those using commercial formulas.

This indicates that both treatment options in the study are generally safe for children newly diagnosed with Crohn's disease. Studies involving these treatments reported no major side effects, which is reassuring for those considering participation in this clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments because they offer a new approach to managing Crohn's Disease through diet. Unlike traditional treatments that often rely on medications like corticosteroids or immunosuppressants, these dietary interventions use nutrition to potentially ease symptoms. The smoothie arm is unique as it involves a whole-food based approach, allowing patients to prepare and consume a nutrient-rich smoothie at home, which may be more palatable and engaging for some individuals. Meanwhile, the formula arm provides a conventional nutritional formula under expert guidance, aiming to simplify dietary management. Both options explore how dietary changes can impact Crohn's Disease, offering a potentially less invasive and more natural management strategy.

What evidence suggests that this trial's treatments could be effective for Crohn's disease?

Research has shown that using whole-food blended smoothies as the sole source of nutrition can be very effective for children with Crohn's disease. One study found that 80% of children who tried this smoothie method experienced significant symptom improvement, achieving remission. In this trial, participants in the smoothie arm will prepare these smoothies at home, offering a natural and potentially more enjoyable way to manage Crohn's symptoms. Participants in the formula arm will receive conventional formula, which previous studies have shown to be as effective as the smoothie method. Early research also suggests that whole foods might benefit gut health. This method could offer a refreshing alternative to standard formulas, which some find less appealing. ^{1 2 3 6 7}

Who Is on the Research Team?

Dale Lee, MD, MSCE

Principal Investigator

Seattle Children's Hospital, University of Washington

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 8-21 who have been diagnosed with Crohn's disease within the last two years. They must show active symptoms, as indicated by a specific activity index score (PCDAI ≥10) and elevated inflammation markers. Participants or their guardians must be able to give informed consent.

Inclusion Criteria

I am between 8 and 21 years old.

Elevation in objective inflammatory markers at enrollment: C-reactive protein (CRP), ESR, or fecal calprotectin

Participant capable of giving informed consent, or if a minor the parent/guardian is capable of giving informed consent

Exclusion Criteria

I have not taken corticosteroids in the last 4 weeks.

I have used biological medication before.

I was hospitalized because my Crohn's disease got very severe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either conventional formula or whole-food blended smoothie EEN for 8 weeks

8 weeks

3 visits (in-person) at week 2, week 4, and week 8

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Formula
• Whole-food based smoothie

Trial Overview The study compares traditional formula-based Exclusive Enteral Nutrition (EEN) with a whole-food based smoothie EEN in treating pediatric Crohn's disease. It will assess which method is more tolerable, effective, and how they affect life quality and gut bacteria over an 8-week period.

How Is the Trial Designed?

Group I: Smoothie Experimental Treatment 1 Intervention

In the smoothie arm, you will be provided instructions, a blender, and food components to prepare the smoothie at home.

Group II: Formula Active Control 1 Intervention

In the formula arm, you will be given conventional formula as per the direction of the gastroenterology team along with our dieticians.

Formula is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Infant Formula for:

• Nutritional support for infants

Approved in United States as Baby Formula for:

• Nutritional support for infants
• Supplementation for breastfeeding

Approved in Canada as Infant Formula for:

• Nutritional support for infants
• Supplementation for breastfeeding in well-baby units

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Dalhousie University

Collaborator

Trials

177

Recruited

402,000+

Published Research Related to This Trial

A systematic review of six studies involving 219 participants suggests that blended diets (BD) may improve symptoms of diarrhea in adults and children who are tube-fed, which is significant given the prevalence of diarrhea in this population.

While the evidence is not strong enough to draw definitive conclusions about other gastrointestinal symptoms like vomiting or bloating, the potential benefits of BD for diarrhea support its consideration as an alternative to commercial feeds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review examining the impact of blended diets on the gastrointestinal symptoms of people who are enterally fed. Peers, E., Boocock, RC., Burn, N.[2023]

Enteral feeding with a whole protein-based formula was found to be as effective as high-dose corticosteroids in achieving clinical remission in children with Crohn's disease, based on a study of 19 participants over 11 weeks.

The enteral feeding group had a lower relapse rate during follow-up (1 relapse) compared to the corticosteroid group (5 relapses), and no side effects were reported from the enteral feeding, suggesting it may be a safer long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exclusive whole protein enteral diet versus prednisolone in the treatment of acute Crohn's disease in children. Ruuska, T., Savilahti, E., Mäki, M., et al.[2022]

In a study of 65 children and adolescents with active Crohn's disease, those who continued nocturnal enteral nutrition after resuming a normal diet experienced a longer remission period compared to those who stopped the supplements.

Continuing enteral nutrition before puberty not only helped maintain remission but also contributed to improved linear growth, highlighting its potential benefits in managing Crohn's disease in young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementary enteral nutrition maintains remission in paediatric Crohn's disease. Wilschanski, M., Sherman, P., Pencharz, P., et al.[2022]

In a study involving seven children with active small bowel Crohn's disease, a casein-based polymeric diet led to significant improvements in disease activity, including normalization of C-reactive protein levels and increased serum albumin after 8 weeks.

The diet resulted in reduced mucosal inflammation in six out of seven children, with complete healing observed in two, suggesting that polymeric diets can be an effective therapeutic option for managing Crohn's disease in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polymeric nutrition as the primary therapy in children with small bowel Crohn's disease. Beattie, RM., Schiffrin, EJ., Donnet-Hughes, A., et al.[2019]

In a study of 58 pediatric patients with short bowel syndrome (SBS), those who received blenderized feeds showed improved gastrointestinal symptoms, particularly reduced diarrhea, although they experienced increased gas.

Patients with colonic resection were more likely to discontinue blenderized feeds, and a subgroup of patients who lost weight despite improved diarrhea often had a history of ileocecal valve and colonic resection, suggesting that careful management and titration of these feeds may be necessary for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blenderized enteral nutrition in pediatric short gut syndrome: Tolerance and clinical outcomes. Zong, W., Troutt, R., Merves, J.[2023]

Regular monitoring of nutrition is crucial for managing Crohn's disease, as many patients experience macro- and micronutrient deficiencies, particularly after surgeries or with extensive small bowel involvement.

Defined formula liquid diets are an effective anti-inflammatory therapy for Crohn's disease, showing benefits in reducing tissue damage, and should be considered in various clinical scenarios, including severe disease and growth failure in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crohn's disease: nutrition and nutritional therapy. Ferguson, A., Glen, M., Ghosh, S.[2019]

In a 1-year study involving 6 children with Crohn's disease and growth failure, an intermittent defined formula diet led to significant increases in height and weight velocity, indicating improved growth outcomes.

The diet also resulted in decreased prednisone use and improved disease activity, albumin levels, and somatomedin C, suggesting that this dietary intervention can effectively manage both growth failure and disease symptoms in affected children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved growth and disease activity after intermittent administration of a defined formula diet in children with Crohn's disease. Polk, DB., Hattner, JA., Kerner, JA.[2017]

In a 12-week trial involving 78 children with mild to moderate Crohn's disease, the combination of the CD exclusion diet (CDED) and partial enteral nutrition (PEN) was significantly better tolerated than exclusive enteral nutrition (EEN), with 97.5% tolerance for CDED and PEN compared to 73.6% for EEN.

CDED plus PEN led to a higher rate of corticosteroid-free remission at week 12 (75.6%) compared to EEN (45.1%), along with beneficial changes in the fecal microbiome, indicating it may be a more effective dietary intervention for inducing and sustaining remission in children with Crohn's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Levine, A., Wine, E., Assa, A., et al.[2019]

A survey of 41 caregivers revealed that 54% use home-blenderized tube feeding (HBTF) and 34% use commercial real-food containing formulas (CRFCF), with a strong preference for whole foods and natural ingredients in their children's diets.

While caregivers find CRFCF convenient and nutritionally consistent, they express a desire for more real-food ingredients, and face challenges with both HBTF and CRFCF, such as preparation difficulties and cost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caregivers' Perceptions of Real-Food Containing Tube Feeding: A Canadian Survey. Boston, M., Wile, H.[2021]

The Crohn's disease exclusion diet (CDED) is a new, patient-friendly dietary therapy that effectively manages pediatric Crohn's disease (CD) by reducing exposure to harmful dietary components, making it a sustainable alternative to exclusive enteral nutrition (EEN).

CDED, especially when combined with partial enteral nutrition, is shown to be a safe and effective option for both inducing and maintaining remission in children with mild to moderate CD, promoting mucosal healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crohn's disease exclusion diet in children with Crohn's disease: a case series. Scarallo, L., Banci, E., Pierattini, V., et al.[2021]

Partial enteral nutrition (PEN) was found to be partially effective in maintaining remission in pediatric Crohn's disease patients, with a median remission length of 6 months after transitioning from exclusive enteral nutrition (EEN).

While PEN helped increase the mean body mass index (BMI) from 18.1 to 18.8 and reduced the weighted Pediatric Crohn Disease Activity Index (wPCDAI) from 30 to 7.5, most patients still needed additional medications to maintain remission after starting PEN.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance of Remission with Partial Enteral Nutrition Therapy in Pediatric Crohn's Disease: A Retrospective Study. Schulman, JM., Pritzker, L., Shaoul, R.[2019]

Enteral feeding can be an effective primary therapy for Crohn's disease, especially in adolescents with growth failure when corticosteroids are not suitable, as it helps avoid the side effects of steroids.

While the exact mechanisms of how enteral feeding works are not fully understood, studies suggest that low-fat diets may enhance efficacy and that identifying and excluding certain foods can help prolong remission in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review article: the dietary management of Crohn's disease. King, TS., Woolner, JT., Hunter, JO.[2019]

In a study comparing liquid diet therapy (LDT) in children with active Crohn's disease, whole-protein polymeric formula (PF) did not significantly improve adherence compared to amino acid-based elemental formula (EF), with completion rates of 58% for PF and 72% for EF.

However, PF was associated with a significantly lower need for nasogastric tube administration (31% for PF vs. 55% for EF), suggesting it may be easier to consume despite similar remission rates between the two formulas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does polymeric formula improve adherence to liquid diet therapy in children with active Crohn's disease? Rodrigues, AF., Johnson, T., Davies, P., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06216899

Reverse-Engineering of Exclusive Enteral Nutrition (RE ... This study will compare the tolerability and efficacy of conventional formula Exclusive Enteral Nutrition (EEN) and whole-food blended smoothie EEN by enrolling ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38558411/

Reverse-engineered exclusive enteral nutrition in pediatric ... This study assessed a whole-food smoothie as EEN for pediatric Crohn's. 80% of participants achieved remission, and it was effective similar to commercial ...

3. seattlechildrens.org seattlechildrens.org/healthcare-professionals/provider-news/smoothie-study/

Smoothie Study Examines Possible Benefits of Additive- ... “EEN is very effective for some individuals with Crohn's disease,” Lee says. ... To test the hypothesis that a whole-foods-based nutritional ...

4. chop.edu chop.edu/research-studies/re-een-smoothie-study

RE-EEN Smoothie Study The RE-EEN study evaluates a whole-food smoothie as Exclusive Enteral Nutrition for Crohn's Disease, comparing it to formula. Participants are 8-21 years old.

5. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/when-food-is-medicine-updated-evidence-on-nutritional-therapies-and-pediatric-ibd

Updated Evidence on Nutritional Therapies and Pediatric IBD Whole food blended smoothie. Promising results from a small pilot trial show that a whole food blended smoothie, created with micro and ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2405457725003092

From traditional to artificial intelligence-driven approaches ... This review aims to summarize accumulating data on the effects of dietary interventions in IBD patients and introduce the role of artificial intelligence (AI)

7. researchgate.net researchgate.net/publication/379452991_Reverse-engineered_exclusive_enteral_nutrition_in_pediatric_Crohn's_disease_A_pilot_trial

(PDF) Reverse-engineered exclusive enteral nutrition in ... A whole-food blended smoothie was effective for inducing clinical remission and decreasing FCP in pediatric CD similar to commercial EEN formulas.