2'-FL Supplement for Inflammatory Bowel Disease
(PRIME Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
Trial Summary
What is the purpose of this trial?This trial tests 2'-FL, a sugar from breast milk, as a dietary supplement for young IBD patients in stable remission. It aims to boost good gut bacteria and improve gut health by increasing butyrate levels. 2'-FL, a human milk oligosaccharide, has been shown to promote the growth of beneficial gut bacteria and improve gut health in various studies.
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.
What data supports the effectiveness of the treatment 2'-Fucosyllactose for Inflammatory Bowel Disease?
Research shows that 2'-Fucosyllactose, a compound found in human milk, can help improve gut health by strengthening the intestinal barrier and reducing inflammation. Studies in mice with colitis, a type of inflammatory bowel disease, found that 2'-Fucosyllactose helped maintain body weight, protect colon length, and lower inflammation markers, suggesting it may be beneficial for similar conditions in humans.
12345Is 2'-FL safe for human consumption?
2'-Fucosyllactose (2'-FL) is considered safe for human consumption under the proposed conditions of use, as it is similar to natural components found in human milk. The European Food Safety Authority (EFSA) has evaluated its safety and found no concerns when used in foods and supplements, with intake levels comparable to those in breastfed infants.
15678How does the 2'-FL treatment differ from other treatments for inflammatory bowel disease?
The 2'-FL treatment is unique because it is a prebiotic oligosaccharide found in human milk that promotes the growth of beneficial gut bacteria and increases short-chain fatty acids like butyrate, which can improve gut health. Unlike traditional treatments that may focus on reducing inflammation directly, 2'-FL works by enhancing the gut microbiome, potentially leading to improved gastrointestinal symptoms and quality of life in patients with conditions like ulcerative colitis.
19101112Eligibility Criteria
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.
+11 more
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.
+6 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: 2'-FucosyllactoseExperimental Treatment1 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: PlaceboPlacebo Group1 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Connecticut Children's Medical CenterHartford, CT
Nationwide Children's HospitalColumbus, OH
Cincinnati Children's Hospital Medical CenterCincinnati, OH
Loading ...
Who Is Running the Clinical Trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
Nationwide Children's HospitalCollaborator
Broad Institute of MIT and HarvardCollaborator
Broad InstituteCollaborator
University of CincinnatiCollaborator
Connecticut Children's Medical CenterCollaborator
References
2'-Fucosyllactose Ameliorates Chemotherapy-Induced Intestinal Mucositis by Protecting Intestinal Epithelial Cells Against Apoptosis. [2022]Intestinal mucositis, a severe complication of antineoplastic therapeutics, is characterized by mucosal injury and inflammation in the small intestine. Therapies for the prevention and treatment of this disease are needed. We investigated whether 2'-fucosyllactose (2'-FL), an abundant oligosaccharide in human milk, protects intestinal integrity and ameliorates intestinal mucositis.
Effect of soluble fiber or fructooligosaccharide supplementation upon trinitrobenzenesulphonic acid induced colitis in rats. [2019]To evaluate the effect of soluble fiber or fructooligosaccharide (FOS) supplementation upon trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats.
Blends of Human Milk Oligosaccharides Confer Intestinal Epithelial Barrier Protection in Vitro. [2021]Breastfeeding is integral in the proper maturation of the intestinal barrier and protection against inflammatory diseases. When human milk (HM) is not available, supplementation with HM bioactives like Human Milk Oligosaccharides (HMOs) may help in providing breastfeeding barrier-protective benefits. An increasing HMO variety is becoming industrially available, enabling approaching the HMO complexity in HM. We aimed at assessing the impact of blends of available HMOs on epithelial barrier function in vitro. The capacity of individual [2'-Fucosyllactose (2'FL), Difucosyllactose, Lacto-N-tetraose, Lacto-N-neotetraose, 3'-Siallylactose and 6'-Siallylactose] or varying combinations of 3, 5 and 6 HMOs to modulate fluorescein-isothiocyanate (FITC)-labelled Dextran 4 KDa (FD4) translocation and/or transepithelial resistance (TEER) was characterized in Caco-2: HT29- methotrexate (MTX) cell line monolayers before and after an inflammatory challenge with TNF-α and IFN-γ. The six HMO blend (HMO6) dose-dependently limited the cytokine-induced FD4 translocation and TEER decrease and increased TEER values before challenge. Similarly, 3 and 5 HMO blends conferred a significant protection against the challenge, with 2'FL, one of the most abundant but most variable oligosaccharides in HM, being a key contributor. Overall, our results suggest differential ability of specific HMOs in modulating the intestinal barrier and support the potential of supplementation with combinations of available HMOs to promote gut health and protect against intestinal inflammatory disorders.
Is a low FODMAP diet beneficial for patients with inflammatory bowel disease? A meta-analysis and systematic review. [2019]To assess the current evidence regarding the benefit of a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol (FODMAP) diet in the treatment of patients with inflammatory bowel disease (IBD).
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. [2023]Ulcerative colitis is an inflammatory bowel disease (IBD) with relapsing and remitting patterns, and it is caused by varied factors, such as the intestinal inflammation extent and duration. We examined the preventative effects of human milk oligosaccharides (HMOs) on epithelial barrier integrity and intestinal inflammation in an interleukin (IL)-6-induced cell model and dextran sodium sulfate (DSS)-induced acute mouse colitis model. HMOs including 2'-fucosyllactose (FL) and 3-FL and positive controls including fructooligosaccharide (FOS) and 5-acetylsalicylic acid (5-ASA) were orally administrated once per day to C57BL/6J mice with colitis induced by 5% DSS in the administered drinking water. 2'-FL and 3-FL did not affect the cell viability in Caco-2 cells. Meanwhile, these agents reversed IL-6-reduced intestinal barrier function in Caco-2 cells. Furthermore, 2'-FL and 3-FL reversed the body weight loss and the remarkably short colon lengths in DSS-induced acute colitis mice. Moreover, 2'-FL and 3-FL obviously protected the decreasing expression of zonula occluden-1 and occludin in colon tissue relative to the findings in the DSS-treated control group. 2'-FL and 3-FL significantly reduced IL-6 and tumor necrosis factor-α levels in serum relative to the control findings. The summary of these results shows that HMOs prevent colitis mainly by enhancing intestinal barrier function and advancing anti-inflammatory responses. Therefore, HMOs might suppress inflammatory responses and represent candidate treatments for IBD that protect intestinal integrity.
Safety of 2'-fucosyllactose (2'-FL) produced by a derivative strain (Escherichia coli SGR5) of E. coli W (ATCC 9637) as a Novel Food pursuant to Regulation (EU) 2015/2283. [2023]Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 2'-fucosyllactose (2'-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 2'-FL, but it also contains d-lactose, l-fucose, fucosylgalactose, difucosyllactose, d-glucose and d-galactose, and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli SGR5) of E. coli W (ATCC 9637). The information provided on the identity, manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant applies for the same use and use levels as already authorised for 2'-FL and included in the Union list of NFs, with the general population as target population. The Panel noted that the available intake estimate is not recent (2015) and based on a different database (2008-2010 UK data) than that used by EFSA. For this reason, the Panel decided to perform a new intake estimate according to the current EFSA approach. The Panel notes that the highest P95 daily intake of the NF from the use as food ingredient is higher than the estimated natural highest mean daily intake in breastfed infants and marginally higher in young children. The applicant also proposes to extend the use of 2'-FL in food supplements (FS) for infants at the use level of 1.2 g/day. The resulting estimated intake in infants from the proposed use in FS is within the natural intake of 2'-FL in breastfed infants. FS are not intended to be used if other foods with added 2'-FL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.
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. [2023]Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 3-fucosyllactose (3-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 3-FL, but it also contains d-lactose, l-fucose, 3-fucosyllactulose and a small fraction of other related saccharides. The NF is produced by fermentation by a genetically modified strain (Escherichia coli K-12 DH1 MDO MAP1834) of E. coli K-12 DH1 (DSM 4235). The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF to a variety of foods, including infant formula and follow-on formula, food for special medical purposes and food supplements (FS). The target population is the general population. The anticipated daily intake of 3-FL from both proposed and combined (authorised and proposed) uses at their respective maximum use levels in all population categories does not exceed the highest intake level of 3-FL from human milk in infants on a body weight basis. The intake of 3-FL in breastfed infants on a body weight basis is expected to be safe also for other population groups. The intake of other carbohydrate-type compounds structurally related to 3-FL is also considered of no safety concern. FS are not intended to be used if other foods with added 3-FL or human milk are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.
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. [2022]Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 2'-fucosyllactose (2'-FL) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is mainly composed of the human-identical milk oligosaccharide (HiMO) 2'-FL, but it also contains d-lactose, l-fucose, 3-fucosyllactose, difucosyllactose, d-glucose and d-galactose. The NF is produced by fermentation with a genetically modified strain (APC199) of Corynebacterium glutamicum ATCC 13032. 2'-FL, when chemically synthesised or produced by fermentation with derivative strains of Escherichia coli K-12 DH1 or E. coli BL21 (DE3), is already authorised and included in the EU list of NFs. This application refers to a change in the production process and specifications, while target population, conditions of use and consequently, the anticipated intake remain unchanged. The information provided on the identity, production process, composition and specifications of the NF does not raise safety concerns. The intake of other carbohydrate-type compounds structurally related to 2'-FL is also considered of no safety concern. In line with other milk oligosaccharides that are natural components of human milk, the safety assessment of this NF is mainly based on the comparison between the intake of breastfed infants and the estimated intake as NF. Given that the NF would be consumed at the same extent as the already authorised 2'-FL, the Panel considers that the consumption of the NF at the proposed uses and use levels does not raise safety concerns. The Panel concludes that the NF is safe under the proposed conditions of use.
Improved production of 2'-fucosyllactose in engineered Saccharomyces cerevisiae expressing a putative α-1, 2-fucosyltransferase from Bacillus cereus. [2021]2'-fucosyllactose (2'-FL) is one of the most abundant oligosaccharides in human milk. It constitutes an authorized functional additive to improve infant nutrition and health in manufactured infant formulations. As a result, a cost-effective method for mass production of 2'-FL is highly desirable.
Whole cell biosynthesis of a functional oligosaccharide, 2'-fucosyllactose, using engineered Escherichia coli. [2021]2'-Fucosyllactose (2-FL) is a functional oligosaccharide present in human milk which protects against the infection of enteric pathogens. Because 2-FL can be synthesized through the enzymatic fucosylation of lactose with guanosine 5'-diphosphate (GDP)-l-fucose by α-1,2-fucosyltransferase (FucT2), an 2-FL producing Escherichia coli can be constructed through overexpressing genes coding for endogenous GDP- l-fucose biosynthetic enzymes and heterologous fucosyltransferase.
Metabolic Fate and Distribution of 2´-Fucosyllactose: Direct Influence on Gut Microbial Activity but not on Brain. [2023]2´-Fucosyllactose (2´FL) is an abundant oligosaccharide in human milk. It is hypothesized that its brain enrichment is associated with improved learning. Accumulation of 2´FL in organs, biological fluids, and feces is assessed in wild-type and germ-free mice.
Impact of 2'-Fucosyllactose on Gut Microbiota Composition in Adults with Chronic Gastrointestinal Conditions: Batch Culture Fermentation Model and Pilot Clinical Trial Findings. [2021]Intestinal dysbiosis has been described in patients with certain gastrointestinal conditions including irritable bowel syndrome (IBS) and ulcerative colitis. 2'-fucosyllactose (2'-FL), a prebiotic human milk oligosaccharide, is considered bifidogenic and butyrogenic. To assess prebiotic effects of 2'-FL, alone or in combination with probiotic strains (potential synbiotics), in vitro experiments were conducted on stool from healthy, IBS, and ulcerative colitis adult donors. In anaerobic batch culture fermenters, Bifidobacterium and Eubacterium rectale-Clostridium coccoides counts, and short-chain fatty acids (SCFAs) including butyrate increased during fermentation with 2'-FL and some of the 2'-FL/probiotic combinations. In a subsequent open-label pilot trial, the effect of a 2'-FL-containing nutritional formula was evaluated in twelve adults with IBS or ulcerative colitis. Gastrointestinal Quality of Life Index (GIQLI) total and gastrointestinal symptoms domain scores, stool counts of Bifidobacterium and Faecalibacterium prausnitzii, and stool SCFAs including butyrate, increased after six weeks of intervention. Consistent with documented effects of 2'-FL, the batch culture fermentation experiments demonstrated bifidogenic and butyrogenic effects of 2'-FL during fermentation with human stool samples. Consumption of the 2'-FL-containing nutritional formula by adults with IBS or ulcerative colitis was associated with improvements in intra- and extra-intestinal symptoms, and bifidogenic and butyrogenic effects.