Oral 2'-Fucosyllactose Supplementation for Bone Marrow Transplant Recipients
Recruiting in Palo Alto (17 mi)
Overseen byPooja Khandelwal, MD
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Waitlist Available
Sponsor: Children's Hospital Medical Center, Cincinnati
No Placebo Group
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?
This trial tests a sugar supplement called 2'-fucosyllactose (2FL) to help children and young adults who have had a stem cell transplant. These patients often suffer from gut problems due to their treatment. The supplement is expected to increase good gut bacteria, reduce bad bacteria, and lower inflammation, leading to better overall health outcomes. 2'-Fucosyllactose (2'-FL) is a natural prebiotic found in human milk and is known for promoting beneficial gut bacteria and improving immune function.
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking anti-diarrheal medications or have taken probiotics or prebiotics in the past month.
What data supports the idea that Oral 2'-Fucosyllactose Supplementation for Bone Marrow Transplant Recipients is an effective treatment?
The available research shows that 2'-Fucosyllactose (2'-FL) can help protect the gut and reduce inflammation. For example, studies have found that 2'-FL can decrease the severity of intestinal inflammation in mice and protect intestinal cells from damage. While there is no direct evidence from the provided research specifically about bone marrow transplant recipients, the positive effects of 2'-FL on gut health and inflammation suggest it could be beneficial for these patients, who often experience gut-related complications. Additionally, a pilot study suggests that human milk, which contains 2'-FL, may reduce intestinal inflammation after bone marrow transplants.12345
What safety data exists for 2'-Fucosyllactose supplementation?
The safety data for 2'-Fucosyllactose (2'-FL) and related compounds like 3-Fucosyllactose (3-FL) indicate that they are generally recognized as safe (GRAS). Studies have shown no acute oral toxicity, genetic toxicity, or subchronic toxicity. 3-FL, a similar compound, has been evaluated for safety in various studies, including acute oral toxicity tests, genetic toxicity assessments, and subchronic rodent feeding studies, all of which support its safe use as a nutritional ingredient in foods. The European Food Safety Authority (EFSA) has also concluded that 3-FL is safe under proposed conditions of use in foods, including infant formulas and food supplements. These findings suggest that 2'-FL, as part of human milk oligosaccharides, is likely safe for consumption in similar contexts.678910
Is 2'-fucosyllactose a promising treatment for bone marrow transplant recipients?
Yes, 2'-fucosyllactose is a promising treatment because it helps protect the intestines from damage during chemotherapy, supports healthy gut bacteria, and prevents harmful bacteria from sticking to cells. It is also well-tolerated in studies, showing no negative effects on growth or health.19111213
Eligibility Criteria
This trial is for patients of any age and diagnosis who are scheduled for an allogeneic stem cell transplant. It's not suitable for those unable to take oral supplements, actively breastfeeding infants, anyone with a recent GI infection or taking anti-diarrheal meds, and people who've used probiotics/prebiotics recently or have had significant gut damage in the past 3 months.Inclusion Criteria
My treatment plan is flexible regarding age, diagnosis, and stem cell sources.
I am scheduled for a stem cell transplant from a donor.
Exclusion Criteria
I have not had severe gut damage or infections in the last 3 months.
I have a history of inflammatory bowel disease, short bowel syndrome, or bowel surgery.
Actively breastfeeding infants
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Treatment Details
Interventions
- 2'-fucosyllactose (Oligosaccharide)
Trial OverviewThe trial tests if adding a supplement called 2'-fucosyllactose (2FL) can help balance gut bacteria and reduce inflammation after bone marrow transplants. The goal is to see if it makes the intestines healthier by day+30 post-transplant and lowers complications like acute GVHD and bloodstream infections by day+100.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: 2'-fucosyllactose for ages >10 yearsExperimental Treatment1 Intervention
Dose for ages \>10 years: 10 g/day;
Group II: 2'-fucosyllactose for ages 5.1-10 yearsExperimental Treatment1 Intervention
Dose for ages 5.1-10 years: 5 g/day;
Group III: 2'-fucosyllactose for ages 0-5 yearsExperimental Treatment1 Intervention
Dose for ages 0-5 years: 2.5 g/day;
2'-fucosyllactose is already approved in Australia, European Union, United States for the following indications:
๐ฆ๐บ Approved in Australia as 2'-Fucosyllactose for:
- Infant nutrition supplement
๐ช๐บ Approved in European Union as 2'-Fucosyllactose for:
- Infant nutrition supplement
๐บ๐ธ Approved in United States as 2'-Fucosyllactose for:
- Infant nutrition supplement
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cincinnati Children's HospitalCincinnati, OH
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Who Is Running the Clinical Trial?
Children's Hospital Medical Center, CincinnatiLead Sponsor
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.
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-ฮฑ and IFN-ฮณ. 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.
Alleviation of Intestinal Inflammation by Oral Supplementation With 2-Fucosyllactose in Mice. [2020]Milk oligosaccharides exert a prebiotic action that contributes to the development of the infant gut microbiota during lactation. Given that milk oligosaccharides remain intact after passage through stomach and small intestine, they can potentially influence the composition of the gut microbiota when ingested as dietary supplements after weaning. To address the regulatory effects of specific oligosaccharides in colitis linked to the microbiota composition, we have supplemented interleukin-10 null (Il10 -/-) mice with four fucosylated and sialylated oligosaccharides. We found that oral supplementation with 2-fucosyllactose significantly decreased the severity of colitis as displayed by reduced inflammatory marker expression, histological and diarrhea scores, an increased epithelial integrity and less pronounced colon shortening. Oral supplementation with 2-fucosyllactose led to a marked expansion of the commensal Ruminococcus gnavus, which was accompanied by an enhanced cecal concentration of propionate. Decreased activation of immune cells by R. gnavus was confirmed by reconstitution of antibiotic-treated Il10 -/- mice and by stimulation of dendritic cells in vitro. This study demonstrates that post-weaning administration of specific oligosaccharides can shift the composition of the gut microbiota to lessen chronic inflammation as observed in Il10 -/- mice. The expansion of R. gnavus sets a positive microbial environment at the cost of pro-inflammatory Gram-negative bacteria, thereby lowering intestinal inflammation.
Nutritional modulation of the gut microbiome in allogeneic hematopoietic stem cell transplantation recipients. [2022]Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potentially curative strategy for many oncological and non-oncological diseases, but it is associated with marked morbidity and mortality. The disruption of gut microbiota (GM) eubiosis has been linked to major allo-HSCT complications, including infections and acute graft vs. host disease (aGvHD), and correlates with mortality. This increasing knowledge on the role of the GM in the allo-HSCT procedure has led to fascinating ideas for modulating the intestinal ecosystem in order to improve clinical outcomes. Nutritional strategies, either by changing the route of nutritional supplementation or by administering specific molecules, are increasingly being considered as cost- and risk-effective methods of modulating the GM. Nutritional support has also emerged in the past several years as a key feature in supportive care for allo-HSCT recipients, and deterioration of nutritional status is associated with decreased overall survival and higher complication rates during treatment. Herein we provide a complete overview focused on nutritional modulation of the GM in allo-HSCT recipients. We address how pre transplant diet could affect GM composition and its ability to withstand the upsetting events occurring during transplantation. We also provide a complete overview on the influence of the route of nutritional administration on the intestinal ecosystem, with a particular focus on the comparison between enteral and parenteral nutrition (PN). Moreover, as mounting evidence are showing how specific components of post-transplant diet, such as lactose, could drastically shape the GM, we will also summarize the role of prebiotic supplementation in the modulation of the intestinal flora and in allo-HSCT outcomes.
A Pilot Study of Human Milk to Reduce Intestinal Inflammation After Bone Marrow Transplant. [2020]Human milk administration in the early peritransplant period would lower intestinal inflammation after bone marrow transplant (BMT).
Safety assessment of the biotechnologically produced human-identical milk oligosaccharide 3-Fucosyllactose (3-FL). [2020]3-Fucosyllactose (3-FL), a highly abundant complex carbohydrate in human breast milk, functions as a prebiotic promoting early microbial colonization of the gut, increasing pathogen resistance and modulating immune responses. To investigate potential health benefits, 3-FL was produced by fermentation using a genetically modified E. coli K12 strain. The safety assessment of 3-FL included acute oral toxicity, in vitro and in vivo assessment of genetic toxicity, and a subchronic rodent feeding study. 3-FL was not acutely toxic at 5000 mg/kg bw, and there was no evidence of genetic toxicity in the bacterial reverse mutation test and chromosomal aberration assay. There was a repeatable statistically-significant trend in the 4-h S9-activated test conditions in the in vitro micronucleus assay; the confirmatory in vivo mouse micronucleus study was negative at all doses. Dietary subchronic exposure of rats to 3-FL (5% and 10%) did not produce any statistical or biologically-relevant differences in growth, food intake or efficiency, clinical observations, or clinical or anatomic pathology changes at average daily intakes of 5.98 and 7.27 g/kg bw/day for males and females, respectively. The weight of evidence from these studies support the safe use of 3-FL produced using biotechnology as a nutritional ingredient in foods.
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.
A safety evaluation of mixed human milk oligosaccharides in rats. [2020]Human milk oligosaccharides (HMOs) are indigestible carbohydrates representing the third largest fraction of solutes in human breastmilk. They provide valuable prebiotic and anti-pathogenic functions in breastfed infants, but are not yet included in most infant formula products. Recent biotechnological advances now facilitate large-scale production of HMOs, providing infant formula manufacturers with the ability to supplement their products with HMOs to mimic human breastmilk. Although the safety of individual HMOs has been confirmed in preclinical toxicological studies, the safety of HMO mixtures has not been tested. We therefore performed bacterial reverse mutation and in vitro micronucleus tests and conducted a repeated-dose oral toxicity study in rats with a mixture of five HMOs (HMO MIX I), containing 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL). HMO MIX I was not genotoxic and did not induce adverse effects in the repeated dose study. The no-observed-adverse-effect-level (NOAEL) for HMO MIX I in this study is 10% in the diet (equivalent to 5.67 g HMO MIX I/kg bw/day for males and 6.97 g HMO MIX I/kg bw/day for females). Our results provide strong evidence for the safety of HMO MIX I in infant products and general foods.
Occurrence, functional properties, and preparation of 3-fucosyllactose, one of the smallest human milk oligosaccharides. [2023]Human milk oligosaccharides (HMOs) are receiving wide interest and high attention due to their health benefits, especially for newborns. The HMOs-fortified products are expected to mimic human milk not only in the kinds of added oligosaccharides components but also the appropriate proportion between these components, and further provide the nutrition and physiological effects of human milk to newborns as closely as possible. In comparison to intensively studied 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL) has less attention in almost all respects. Nerveless, 3-FL naturally occurs in breast milk and increases roughly over the course of lactation with a nonnegligible content, and plays an irreplaceable role in human milk and delivers functional properties to newborns. According to the safety evaluation, 3-FL shows no acute oral toxicity, genetic toxicity, and subchronic toxicity. It has been approved as generally recognized as safe (GRAS). Biological production of 3-FL can be realized by enzymatic and cell factory approaches. The α1,3- or α1,3/4-fucosyltransferase is the key enzyme for 3-FL biosynthesis. Various metabolic engineering strategies have been applied to enhance 3-FL yield using cell factory approach. In conclusion, this review gives an overview of the recent scientific literatures regarding occurrence, bioactive properties, safety evaluation, and biotechnological preparation of 3-FL.
Safety of 3-FL (3-Fucosyllactose) 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 also contains D-lactose and its monomers, L-fucose and a small fraction of other related saccharides. The NF is produced by fermentation with a genetically modified strain of Escherichia coli K-12. 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 in a variety of foods, including infant and follow-on formula, foods for infants and toddlers, foods for special medical purposes and food supplements. The target population is the general population, except for food supplements for which the target population is individuals above 1 year of age. The anticipated daily intake of 3-FL from the NF at the maximum proposed use levels is unlikely to exceed the intake level of breastfed 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. In infants below 1 year of age, a possible exceedance of a natural intake was observed, but the degree of this exceedance is not considered of safety concern in view of the wide range of 3-FL concentrations in human milk. Food supplements are not intended to be used if other foods with the added NF (as well as human milk for young children) are consumed on the same day. The Panel concludes that the NF is safe under the proposed conditions of use.
Metabolic Fate and Distribution of 2ยด-Fucosyllactose: Direct Influence on Gut Microbial Activity but not on Brain. [2023]2ยด-Fucosyllactose (2ยดFL) is an abundant oligosaccharide in human milk. It is hypothesized that its brain enrichment is associated with improved learning. Accumulation of 2ยดFL in organs, biological fluids, and feces is assessed in wild-type and germ-free mice.
A 3-week pre-clinical study of 2โฒ-fucosyllactose in farm piglets. [2017]One of the most abundant oligosaccharides found in human milk is 2โฒ-fucosyllactose, a trisaccharide composed of fucose and lactose, and multiple studies have demonstrated a health benefit to this compound. Recent advances have allowed for the large-scale production of oligosaccharides via fermentation, including 2โฒ-fucosyllactose. A neonatal piglet model was used to evaluate the tolerability of 2โฒ-fucosyllactose, produced through this process, in order to demonstrate the suitability of this compound for human infants under 12 weeks of age. Crossbred farm piglets, at lactation day 2, were assigned to one of four treatment groups receiving a liquid diet containing 0, 200, 500 or 2000 mg/L of 2โฒ-fucosyllactose. The calculated consumption of 2โฒ-fucosyllactose corresponded to dose levels of 29.37, 72.22 and 291.74 mg/kg/day, respectively, in males and 29.30, 74.31, and 298.99 mg/kg/day, respectively in females. Piglets were administered diet for 3 weeks; and there were no test article-related effects on growth and development (clinical observations, body weight and food consumption), clinical pathology parameters (hematology, clinical chemistry, coagulation and urinalysis), or any histopathologic changes. Therefore, dietary exposure to 2โฒ-fucosyllactose at concentrations up to 2000 mg/L was well tolerated by neonatal farm piglets and did not result in adverse health effects or impact piglet growth.
Bioengineered 2'-fucosyllactose and 3-fucosyllactose inhibit the adhesion of Pseudomonas aeruginosa and enteric pathogens to human intestinal and respiratory cell lines. [2019]Human milk oligosaccharides help to prevent infectious diseases in breastfed infants. Larger scale testing, particularly in animal models and human clinical studies, is still limited due to shortened availability of more complex oligosaccharides. The purpose of this study was to evaluate 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) synthesized by whole-cell biocatalysis for their biological activity in vitro. Therefore, we have tested these oligosaccharides for their inhibitory potential of pathogen adhesion in two different human epithelial cell lines. 2'-FL could inhibit adhesion of Campylobacter jejuni, enteropathogenic Escherichia coli, Salmonella enterica serovar fyris, and Pseudomonas aeruginosa to the intestinal human cell line Caco-2 (reduction of 26%, 18%, 12%, and 17%, respectively), as could be shown for 3-FL (enteropathogenic E coli 29%, P aeruginosa 26%). Furthermore, adherence of P aeruginosa to the human respiratory epithelial cell line A549 was significantly inhibited by 2'-FL and 3-FL (reduction of 24% and 23%, respectively). These results confirm the biological and functional activity of biotechnologically synthesized human milk oligosaccharides. Mass-tailored human milk oligosaccharides could be used in the future to supplement infant formula ingredients or as preventatives to reduce the impact of infectious diseases.