2'-FL Supplement for Inflammatory Bowel Disease

(PRIME Trial)

Recruiting at 2 trial locations

Overseen By Ramona Bezold, BSN

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: Anti-TNF therapy

Must not be taking: Antibiotics, Probiotics, Prebiotics

Disqualifiers: Active IBD, Celiac, Diabetes, others

Compensation: Varies

Number of Visits: Unknown

Duration: 20 weeks

116 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new supplement, 2'-Fucosyllactose, for individuals with inflammatory bowel diseases such as Crohn's Disease and ulcerative colitis. Researchers aim to determine if this supplement is safe and can increase beneficial gut bacteria and butyrate, a compound that may enhance gut health. Participants will receive either the supplement or a placebo (a non-active substance) daily while maintaining their current treatments. The trial seeks individuals aged 11-25 who are in stable remission from Crohn's or ulcerative colitis and are on consistent anti-TNF therapy, such as infliximab or adalimumab. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current anti-TNF medication (like adalimumab or infliximab) for at least 12 weeks before joining. If you're taking mesalamine, mercaptopurine, azathioprine, or methotrexate, you must also be on a stable dose for 12 weeks before starting the trial. You cannot use antibiotics, probiotics, prebiotics, or anti-diarrheal medications during the trial.

Is there any evidence suggesting that 2'-Fucosyllactose is likely to be safe for humans?

Research has shown that 2'-fucosyllactose (2'-FL) is generally safe and easy for the body to handle. Studies have found that it can help reduce inflammation in conditions like inflammatory bowel disease (IBD). One study found it safe for preterm infants, indicating its gentleness on the body. Another study confirmed that 2'-FL is well-tolerated in people and does not cause major side effects.

In related research, 2'-FL has helped keep IBD under control, aiding in maintaining remission. Findings from these studies support the idea that 2'-FL can be safely used in humans. Overall, the evidence suggests that 2'-FL is a promising and safe option for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for IBD?

Unlike the standard treatments for Inflammatory Bowel Disease, such as anti-inflammatory drugs, immunosuppressants, and biologics, 2'-Fucosyllactose (2'-FL) is unique because it is a naturally occurring human milk oligosaccharide. Researchers are excited about 2'-FL because it works differently, potentially modulating the gut microbiota and strengthening the gut barrier, which could reduce inflammation in a more natural way. This new mechanism of action offers the promise of fewer side effects compared to traditional therapies, which often suppress the immune system and can lead to complications. By targeting the gut environment itself, 2'-FL could offer a novel approach to managing symptoms and improving the quality of life for patients with conditions like ulcerative colitis and Crohn's disease.

What evidence suggests that 2'-Fucosyllactose could be an effective treatment for inflammatory bowel disease?

Studies have shown that 2'-Fucosyllactose (2'-FL) might benefit individuals with inflammatory bowel disease (IBD), including Crohn's Disease and ulcerative colitis. Research indicates that 2'-FL can enhance gut health by aiding the recovery of the intestinal mucosal barrier, which serves as a protective wall for the gut. It also helps reduce inflammation, a major issue in IBD. Some studies suggest that 2'-FL promotes a healthier gut microbiota, the community of tiny organisms living in the gut. Early findings from animal studies showed that 2'-FL can ease symptoms of colitis, a common problem in IBD. These promising results suggest that 2'-FL might help manage IBD symptoms more effectively. In this trial, participants will receive either 2'-FL or a placebo to evaluate its effectiveness in managing IBD symptoms. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for young people aged 11-25 with Crohn's Disease or Ulcerative Colitis in remission, not on steroids, and taking stable anti-TNF therapy like adalimumab or infliximab. Participants must consent to the study rules and can't be pregnant, breastfeeding, have had recent surgery (except one ileo-colic resection), or been on certain medications.

Inclusion Criteria

Agreement to not make any major dietary changes throughout study duration. This would include changing usual diet to a vegan diet, Specific Carbohydrate Diet (SCD), or exclusive enteral nutrition (EEN) diet.

My child's Crohn's disease is mild.

I am 18-25 years old with mild Crohn's disease symptoms.

Exclusion Criteria

I do not have celiac disease, diabetes, or any other condition that the study leader would exclude.

Currently pregnant or breast feeding

I have lactose intolerance.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2'-FL or dextrose placebo as a daily dietary supplement

20 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 2'-Fucosyllactose

Trial Overview The study tests if a dietary supplement called 2'-Fucosyllactose (2'-FL) at doses of 1, 5, or 10 grams daily is safe and improves gut health compared to a placebo in those with IBD. It's randomized so participants don't choose which treatment they get.

How Is the Trial Designed?

Group I: 2'-Fucosyllactose Experimental Treatment 1 Intervention

Phase I: 36 young adult participants aged 18-25 years. Group 1: 1 gm per day n=12 (6UC/6CD) Group 2: 5 gm per day n=12 (6UC/6CD) Group 3: 10 gm per day n=12 (6UC/6CD) Phase II (post Phase I interim safety analysis): 120 participants aged 11-25 years Group 1: 1 gm per day n=40 (20UC/20CD) Group 2: 5 gm per day n=40 (20UC/20CD) Group 3: 10 gm per day n=40 (20UC/20CD)

Group II: Placebo Placebo Group 1 Intervention

Phase I: 20 young adult participants age 18-25 years dosed at 2 gm placebo per day. (10UC/10CD) Phase II (post Phase I interim safety analysis): 40 participants age 11-25 years dosed at 2 gm placebo per day. (20UC/20CD)

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Nationwide Children's Hospital

Collaborator

Trials

354

Recruited

5,228,000+

Broad Institute of MIT and Harvard

Collaborator

Trials

21

Recruited

16,300+

Broad Institute

Collaborator

Trials

21

Recruited

16,300+

University of Cincinnati

Collaborator

Trials

442

Recruited

639,000+

Connecticut Children's Medical Center

Collaborator

Trials

76

Recruited

30,000+

Published Research Related to This Trial

A new method for producing 2'-fucosyllactose (2'-FL) was developed using genetically engineered yeast (Saccharomyces cerevisiae), achieving a significant production increase to 26.63 g/L through various enhancements, including the use of a specific fucosyltransferase from Bacillus cereus.

This innovative production process shows promise for cost-effective, large-scale manufacturing of 2'-FL, which is important for improving infant nutrition in formula, highlighting its potential for commercial applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved production of 2'-fucosyllactose in engineered Saccharomyces cerevisiae expressing a putative α-1, 2-fucosyltransferase from Bacillus cereus. Xu, M., Meng, X., Zhang, W., et al.[2021]

A low FODMAP diet significantly improves gastrointestinal symptoms in patients with inflammatory bowel disease (IBD), including reductions in diarrhea, abdominal pain, bloating, fatigue, and nausea, based on a meta-analysis of 319 patients.

The analysis indicates that while the diet is effective for most symptoms, it did not show a significant impact on constipation, highlighting the need for further research to confirm these findings and explore long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is a low FODMAP diet beneficial for patients with inflammatory bowel disease? A meta-analysis and systematic review. Zhan, YL., Zhan, YA., Dai, SX.[2019]

In a study involving 64 Wistar rats, supplementation with soluble fiber or fructooligosaccharides (FOS) prior to TNBS-induced colitis did not significantly improve colon health or reverse lesions after 14 days.

While FOS supplementation was associated with an increased colon weight/length ratio, neither treatment showed any beneficial effects on body weight or colon lesions, indicating that these supplements may not be effective in managing TNBS-induced colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of soluble fiber or fructooligosaccharide supplementation upon trinitrobenzenesulphonic acid induced colitis in rats. Murad-Regadas, SM., Souza, MH., Brito, GA., et al.[2019]

Human milk oligosaccharides (HMOs), specifically 2'-fucosyllactose (FL) and 3-FL, were shown to enhance intestinal barrier function and reduce inflammation in both cell and mouse models of ulcerative colitis, indicating their potential as a preventative treatment.

In a mouse model of acute colitis, HMOs significantly improved symptoms such as body weight loss and colon length, while also decreasing levels of inflammatory markers like IL-6 and tumor necrosis factor-α, suggesting they could be effective in managing inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2'-Fucosyllactose and 3-Fucosyllactose Alleviates Interleukin-6-Induced Barrier Dysfunction and Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Modulating the Intestinal Microbiome. Kim, YJ., Kim, HH., Shin, CS., et al.[2023]

The engineered E. coli JM109(DE3) strain successfully produced 2'-Fucosyllactose (2-FL) from lactose, achieving a maximum concentration of 1.23 g/L without needing additional sugars for growth, indicating a promising method for 2-FL production.

The yield of 2-FL was about 20% of the theoretical maximum, suggesting that further metabolic engineering and fermentation optimization could enhance production, making 2-FL more feasible as a prebiotic in food applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole cell biosynthesis of a functional oligosaccharide, 2'-fucosyllactose, using engineered Escherichia coli. Lee, WH., Pathanibul, P., Quarterman, J., et al.[2021]

In vitro experiments showed that 2'-fucosyllactose (2'-FL) increased beneficial bacteria and short-chain fatty acids, indicating its prebiotic effects, particularly in healthy individuals and those with IBS or ulcerative colitis.

A pilot trial with 12 adults demonstrated that a nutritional formula containing 2'-FL improved gastrointestinal quality of life and increased beneficial bacteria after six weeks, suggesting its potential as a therapeutic intervention for IBS and ulcerative colitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of 2'-Fucosyllactose on Gut Microbiota Composition in Adults with Chronic Gastrointestinal Conditions: Batch Culture Fermentation Model and Pilot Clinical Trial Findings. Ryan, JJ., Monteagudo-Mera, A., Contractor, N., et al.[2021]

3-fucosyllactose (3-FL), a novel food derived from a genetically modified strain of E. coli, has been deemed safe for consumption in various food products, including infant formula, based on a comprehensive review by the EFSA involving its manufacturing process and composition.

The anticipated daily intake of 3-FL from proposed uses does not exceed levels found in human milk, suggesting it is safe for the general population, including infants, and poses no safety concerns when consumed alongside other carbohydrate compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 3-fucosyllactose (3-FL) produced by a derivative strain of Escherichia coli K-12 DH1 as a novel food pursuant to Regulation (EU) 2015/2283. Turck, D., Bohn, T., Castenmiller, J., et al.[2023]

Supplementation with blends of Human Milk Oligosaccharides (HMOs) can enhance intestinal barrier function, particularly in the presence of inflammatory challenges, as shown in vitro using Caco-2: HT29 cell line monolayers.

The six-HMO blend (HMO6) was particularly effective in reducing harmful translocation of substances and improving barrier integrity, indicating that specific combinations of HMOs could be beneficial for gut health and protection against inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blends of Human Milk Oligosaccharides Confer Intestinal Epithelial Barrier Protection in Vitro. Natividad, JM., Rytz, A., Keddani, S., et al.[2021]

2'-Fucosyllactose (2'-FL), a sugar found in human milk, was shown to protect small intestinal epithelial cells from damage caused by the chemotherapy drug 5-fluorouracil (5-FU), reducing cell apoptosis and inflammation in mouse models.

Pretreatment with 2'-FL significantly improved outcomes in mice with 5-FU-induced intestinal mucositis, including less body weight loss and reduced intestinal damage, compared to concurrent treatment, highlighting its potential as a preventive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2'-Fucosyllactose Ameliorates Chemotherapy-Induced Intestinal Mucositis by Protecting Intestinal Epithelial Cells Against Apoptosis. Zhao, G., Williams, J., Washington, MK., et al.[2022]

Oral administration of 2'-Fucosyllactose (2'-FL) in wild-type mice leads to its accumulation in the brain and other organs, suggesting that metabolites derived from gut microbes may play a role in this process rather than the intact 2'-FL itself.

In contrast, when 2'-FL is administered intravenously, it is eliminated through urine without enriching organs, indicating that the method of administration significantly affects its bioavailability and potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Fate and Distribution of 2´-Fucosyllactose: Direct Influence on Gut Microbial Activity but not on Brain. Kuntz, S., Kunz, C., Borsch, C., et al.[2023]

The EFSA Panel concluded that 2'-fucosyllactose (2'-FL), a novel food produced by genetically modified E. coli, is safe for consumption under the proposed conditions of use, including as a food supplement for infants.

The estimated intake of 2'-FL from proposed food supplements is within the natural levels found in breastfed infants, indicating that it can be safely added to infant diets without exceeding typical intake levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 2'-fucosyllactose (2'-FL) produced by a derivative strain (Escherichia coli&#160;SGR5) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283. Turck, D., Bohn, T., Castenmiller, J., et al.[2023]

The EFSA Panel concluded that 2'-fucosyllactose (2'-FL), produced by a genetically modified strain of Corynebacterium glutamicum, is safe for consumption as a novel food, with no safety concerns raised regarding its production process or composition.

The safety assessment was based on comparisons to the intake levels of breastfed infants, confirming that the proposed consumption levels of 2'-FL as a novel food do not pose any safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 2'-fucosyllactose (2'-FL) produced by a derivative strain (APC199) of Corynebacterium glutamicumATCC 13032 as a novel food pursuant to Regulation (EU) 2015/2283. Turck, D., Bohn, T., Castenmiller, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8892212/

Fucosyllactose Ameliorates Inflammatory Bowel Disease ... In conclusion, this study suggests that 2′-FL ameliorates colitis in a gut microbiota-dependent manner. The underlying protective mechanism ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0261561423004491

2'-Fucosyllactose restores the intestinal mucosal barrier in ... 2'-FL promotes the recovery of the intestinal mucosal barrier and suppresses inflammation in ulcerative colitis by inhibiting the palmitoylation and ...

3. journals.asm.org journals.asm.org/doi/10.1128/mbio.00298-24

A human milk oligosaccharide prevents intestinal ... Here, we investigated how 2′-FL prevents colitis in adulthood through its effects on the gut microbial community.

4. grantome.com grantome.com/grant/NIH/R01-HD094862-01

Dosing and Pilot Efficacy of 2'-Fucosyllactose in ... hold promise for restoring healthy gut microbiota in IBD and preventing clinical relapse. Here, we propose the first studies of the prebiotic human milk ...

5. journalofdairyscience.org journalofdairyscience.org/article/S0022-0302(24)01117-2/fulltext

fucosyllactose and galacto-oligosaccharides exerts anti- ... In a mouse model of dextran sulfate sodium (DSS)-induced colitis, combined 2′-FL and GOS supplementation alleviated symptoms, improved gut ...

6. fda.gov fda.gov/media/161879/download

GRAS Notice 1040, 2'-fucosyllactose infant formula, recent clinical data indicate that 2'-FL supplementation is safe and supported normal growth in preterm infants even within ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0958694620301679

Effect of 2′-fucosyllactose supplementation on intestinal ... The results indicated that inflammatory bowel disease was attenuated by consumption of both HMOs and 2′-FL. Moreover, both dietary HMOs and 2′-FL inhibited ...