Oral 2'-Fucosyllactose Supplementation for Bone Marrow Transplant Recipients

Overseen By Celeste Dourson

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: Anti-diarrheals, Probiotics

Disqualifiers: Intestinal failure, Breastfeeding, GI infection, Gut damage, IBD, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 5 weeks

70 Participants Needed

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but 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. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment 2'-fucosyllactose for bone marrow transplant recipients?

Research shows that 2'-fucosyllactose, a component of human milk, can protect the gut lining and reduce inflammation, which may help bone marrow transplant patients by improving gut health and reducing complications. ^{1 2 3 4 5}

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. ^{6 7 8 9 10}

Is 2'-fucosyllactose (2'-FL) safe for human consumption?

2'-Fucosyllactose (2'-FL) is considered safe for human consumption, as studies on similar compounds like 3-fucosyllactose (3-FL) show no acute toxicity, genetic toxicity, or subchronic toxicity. These compounds are naturally found in human breast milk and are used in foods, including infant formulas, without safety concerns. ^{6 7 8 9 10}

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. ^{1 9 11 12 13}

What makes 2'-fucosyllactose unique as a treatment for bone marrow transplant recipients?

2'-Fucosyllactose is unique because it is a compound found in human milk that can protect intestinal cells and reduce inflammation, which may help prevent complications like intestinal mucositis in bone marrow transplant recipients. Unlike other treatments, it is derived from a natural source and has shown potential in improving gut health and preventing infections by inhibiting harmful bacteria from sticking to intestinal cells. ^{1 9 11 12 13}

Research Team

Pooja Khandelwal, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

2'-Fucosyllactose (2FL) supplementation administered from day-7 until day+30 after HSCT

5 weeks

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of GVHD and bloodstream infections

10 weeks

Visits at day+7, day+14, day+30, and day+100

Dose Finding

Dose escalation or de-escalation based on rates of dose limiting toxicities

Ongoing

Treatment Details

Interventions

• 2'-fucosyllactose

Trial Overview The 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

Group I: 2'-fucosyllactose for ages >10 years Experimental Treatment 1 Intervention

Dose for ages \>10 years: 10 g/day;

Group II: 2'-fucosyllactose for ages 5.1-10 years Experimental Treatment 1 Intervention

Dose for ages 5.1-10 years: 5 g/day;

Group III: 2'-fucosyllactose for ages 0-5 years Experimental Treatment 1 Intervention

Dose for ages 0-5 years: 2.5 g/day;

2'-fucosyllactose is already approved in European Union, United States for the following indications:

Approved in European Union as 2'-Fucosyllactose for:

• Infant nutrition supplement

Approved in United States as 2'-Fucosyllactose for:

• Infant nutrition supplement

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Findings from Research

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]

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]

Oral supplementation with the milk oligosaccharide 2-fucosyllactose significantly reduced the severity of colitis in interleukin-10 null (Il10-/-) mice, indicating its potential as a therapeutic agent for gut inflammation.

The treatment led to an increase in beneficial gut bacteria, specifically Ruminococcus gnavus, which helped decrease inflammation by enhancing gut barrier integrity and reducing pro-inflammatory bacteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alleviation of Intestinal Inflammation by Oral Supplementation With 2-Fucosyllactose in Mice. Grabinger, T., Glaus Garzon, JF., Hausmann, M., et al.[2020]

Disruption of gut microbiota is linked to serious complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT), including infections and acute graft vs. host disease, which can increase mortality rates.

Nutritional strategies, such as modifying diet and using prebiotic supplementation, are being explored as effective methods to improve gut microbiota health and clinical outcomes for allo-HSCT recipients, potentially enhancing survival and reducing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional modulation of the gut microbiome in allogeneic hematopoietic stem cell transplantation recipients. Muratore, E., Leardini, D., Baccelli, F., et al.[2022]

In a study involving 46 children undergoing bone marrow transplant, those who received human milk showed significantly lower levels of inflammatory markers like IL-8, IL-10, and REG3α, suggesting that human milk can help reduce intestinal inflammation during recovery.

The human milk group had a lower abundance of harmful bacteria in their stool compared to the control group, indicating that human milk may support a healthier gut microbiome in post-transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of Human Milk to Reduce Intestinal Inflammation After Bone Marrow Transplant. Khandelwal, P., Andersen, H., Romick-Rosendale, L., et al.[2020]

3-Fucosyllactose (3-FL), a prebiotic found in human breast milk, was produced safely using genetically modified E. coli K12, showing no acute toxicity at high doses (5000 mg/kg) and no genetic toxicity in multiple tests.

Subchronic feeding studies in rats revealed that 3-FL did not affect growth, food intake, or health indicators, supporting its safety as a nutritional ingredient in foods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of the biotechnologically produced human-identical milk oligosaccharide 3-Fucosyllactose (3-FL). Pitt, J., Chan, M., Gibson, C., et al.[2020]

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]

A mixture of five human milk oligosaccharides (HMOs) was tested for safety in rats and found to be non-genotoxic and without adverse effects, establishing a no-observed-adverse-effect-level (NOAEL) of 10% in the diet.

These findings support the safety of HMO MIX I for use in infant formula and other food products, paving the way for its inclusion to better mimic the benefits of human breastmilk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A safety evaluation of mixed human milk oligosaccharides in rats. Parschat, K., Oehme, A., Leuschner, J., et al.[2020]

3-Fucosyllactose (3-FL), a naturally occurring oligosaccharide in breast milk, is important for newborn health and has been shown to be safe, with no acute oral toxicity or genetic toxicity, and is recognized as generally safe (GRAS).

The production of 3-FL can be achieved through enzymatic methods and metabolic engineering strategies, highlighting its potential for use in HMO-fortified products that aim to replicate the benefits of human milk for infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occurrence, functional properties, and preparation of 3-fucosyllactose, one of the smallest human milk oligosaccharides. Li, Z., Zhu, Y., Ni, D., et al.[2023]

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

The anticipated daily intake of 3-FL is unlikely to exceed levels typically consumed by breastfed infants, and while there may be slight exceedances in infants under 1 year, these are not deemed a safety concern due to the natural variability of 3-FL in human milk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 3-FL (3-Fucosyllactose) as a novel food pursuant to Regulation (EU) 2015/2283. Turck, D., Castenmiller, J., De Henauw, S., et al.[2023]

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]

In a study using neonatal piglets, 2′-fucosyllactose was well tolerated at concentrations up to 2000 mg/L, with no adverse effects on growth, development, or health parameters over a 3-week period.

The research supports the safety of 2′-fucosyllactose for potential use in human infants under 12 weeks of age, as it showed no negative impacts on clinical observations or pathology in the piglet model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 3-week pre-clinical study of 2′-fucosyllactose in farm piglets. Hanlon, PR., Thorsrud, BA.[2017]

The study demonstrated that synthesized human milk oligosaccharides, specifically 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL), effectively inhibit the adhesion of various pathogens to human epithelial cells, suggesting their potential role in preventing infections in infants.

Both 2'-FL and 3-FL showed significant reductions in pathogen adhesion, with 2'-FL reducing Campylobacter jejuni and Pseudomonas aeruginosa adhesion by up to 26%, indicating their promising use as supplements in infant formula to enhance health and prevent infectious diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioengineered 2'-fucosyllactose and 3-fucosyllactose inhibit the adhesion of Pseudomonas aeruginosa and enteric pathogens to human intestinal and respiratory cell lines. Weichert, S., Jennewein, S., Hüfner, E., et al.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

2'-Fucosyllactose Ameliorates Chemotherapy-Induced Intestinal Mucositis by Protecting Intestinal Epithelial Cells Against Apoptosis. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Blends of Human Milk Oligosaccharides Confer Intestinal Epithelial Barrier Protection in Vitro. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Alleviation of Intestinal Inflammation by Oral Supplementation With 2-Fucosyllactose in Mice. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Nutritional modulation of the gut microbiome in allogeneic hematopoietic stem cell transplantation recipients. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

A Pilot Study of Human Milk to Reduce Intestinal Inflammation After Bone Marrow Transplant. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Safety assessment of the biotechnologically produced human-identical milk oligosaccharide 3-Fucosyllactose (3-FL). [2020]

7. United States 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A safety evaluation of mixed human milk oligosaccharides in rats. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Occurrence, functional properties, and preparation of 3-fucosyllactose, one of the smallest human milk oligosaccharides. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Safety of 3-FL (3-Fucosyllactose) as a novel food pursuant to Regulation (EU) 2015/2283. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

Metabolic Fate and Distribution of 2´-Fucosyllactose: Direct Influence on Gut Microbial Activity but not on Brain. [2023]

12. England pubmed.ncbi.nlm.nih.gov

A 3-week pre-clinical study of 2′-fucosyllactose in farm piglets. [2017]

13. United States pubmed.ncbi.nlm.nih.gov

Bioengineered 2'-fucosyllactose and 3-fucosyllactose inhibit the adhesion of Pseudomonas aeruginosa and enteric pathogens to human intestinal and respiratory cell lines. [2019]