Prebiotic Supplement for Acute GVHD

Overseen By Lauren Hill

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Duke University

Must not be taking: Prebiotics, Probiotics, Herbal supplements, Antibiotics

Disqualifiers: Pregnant, Malabsorption, Grade 2 GI symptoms, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 365

128 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine whether the carbohydrate prebiotic (dietary supplement) known as galacto-oligosaccharide (GOS) can modulate the microbiome (the bacteria in the gut) and help prevent graft-versus host disease (GVHD) after allogeneic stem cell transplant. The study has two two parts. In phase 1, the best dose of GOS will be evaluated. In phase 2, using the best dose of GOS, participants will be randomized to receive GOS or a placebo (maltodextrin, a common food additive that is not known to affect the microbiome) so that the effect of GOS can be determined.

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 be on active treatment with other prebiotics, probiotics, herbal supplements, or antibiotics (except preventive antibiotics) when you enroll.

What data supports the effectiveness of the treatment Galacto-oligosaccharide for acute GVHD?

Research shows that galacto-oligosaccharides (GOS) can promote the growth of beneficial gut bacteria, which may help protect the intestinal barrier during infections. Additionally, GOS has been shown to have a preventive effect against colorectal cancer in animal studies, suggesting potential benefits for gut health. ^{1 2 3 4 5}

Is the prebiotic supplement Galacto-oligosaccharide safe for humans?

Galacto-oligosaccharides (GOS) are generally considered safe for humans, as confirmed by the Food and Drug Administration. They are widely used in food products and have been shown to have beneficial effects on gut health without significant safety concerns. ^{6 7 8 9 10}

How is the prebiotic treatment Galacto-oligosaccharide unique for acute GVHD?

Galacto-oligosaccharide (GOS) is unique because it is a prebiotic that specifically promotes the growth of beneficial gut bacteria like bifidobacteria, which can help improve gut health and potentially modulate immune responses. This is different from traditional treatments for acute GVHD, which often focus on suppressing the immune system rather than enhancing gut microbiota. ^{4 11 12 13 14}

Research Team

Anthony Sung, MD

Principal Investigator

Duke Health

Mitchell Horwitz, MD

Principal Investigator

Duke Health

Eligibility Criteria

Adults aged 18-80 planning to undergo a stem cell transplant for cancer or other illnesses, with a good performance status. Not eligible if using antibiotics (except prophylactic), prebiotics, probiotics, herbal supplements unless stopped before joining; also excluded if pregnant/lactating, have certain digestive conditions, or are in specific other GVHD trials.

Inclusion Criteria

I am mostly able to care for myself and carry out daily activities.

I am between 18 and 80 years old.

I am planning to have a stem cell transplant from a donor.

Exclusion Criteria

I am enrolled in a study for GVHD or not in any conflicting trials.

I am experiencing moderate to severe stomach or intestinal issues.

I am currently taking antibiotics for an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive GOS at dose levels 0.75g, 1.5g, and 2.9g/day to determine the provisional maximum tolerated dose (pMTD)

Approximately 30 days

Daily administration

Phase II Treatment

Participants receive GOS or placebo (maltodextrin) at determined pMTD from about 30 days before transplant to about 4 weeks after transplant

Approximately 8 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and incidence of chronic GVHD

Up to 730 days

Chart reviews at Day 365 and Day 730

Treatment Details

Interventions

• Galacto-oligosaccharide
• Maltodextrin

Trial Overview The trial is testing galacto-oligosaccharide (GOS), a dietary supplement thought to improve gut bacteria and prevent graft-versus-host disease after stem cell transplants. Participants will first help find the best dose of GOS and then be randomly given either GOS or maltodextrin (placebo) to see its effects.

Participant Groups

Group I: Galacto-oligosaccharide Experimental Treatment 1 Intervention

Phase I: Subjects will receive GOS, at dose levels 0.75g, 1.5g, and 2.9 g/day administered once daily. GOS will be dosed per the following schedule using a modified 3+3 design: 0.75g x 4 days, followed by 1.5g x 4 days, followed by 2.9g for the duration of the study starting from about 30 days before transplant to about 4 weeks after transplant. Phase II: Subjects will receive GOS, at dose levels 0.25\*MTD, 0.5\*MTD, and MTD with MTD determined by the phase 1 of the study, once daily from about 30 days before transplant to about 4 weeks after transplant.

Group II: Maltodextrin Placebo Group 1 Intervention

Phase II: Subjects will receive maltodextrin at comparable dose level as GOS (in Phase II) once daily from about 30 days before transplant to about 4 weeks after transplant.

Galacto-oligosaccharide is already approved in European Union, United States for the following indications:

Approved in European Union as Galacto-oligosaccharides for:

• Infant nutrition
• Food additive

Approved in United States as Galacto-oligosaccharides for:

• Dietary supplement
• Food additive

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Findings from Research

In a study of 104 children aged 9-24 months with acute diarrhea, a mixture of prebiotics did lead to a slight decrease in the number of stools and an increase in stool consistency, but these changes were not clinically significant.

The only notable immune response observed was a decrease in TNF-α levels in the supplemented group, indicating some immune modulation, but overall, prebiotic supplementation did not significantly affect the clinical course of acute diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term effect of prebiotics administration on stool characteristics and serum cytokines dynamics in very young children with acute diarrhea. Vaisman, N., Press, J., Leibovitz, E., et al.[2021]

In a study involving 12 healthy adults, the intake of galacto-oligosaccharides (GOS) during and after amoxicillin treatment showed a trend towards higher levels of beneficial bifidobacteria compared to a placebo, suggesting a potential role in gut microbiota recovery.

GOS intake also led to a significant increase in butyrate levels in fecal samples, indicating enhanced metabolic activity of the microbiota, which supports the idea that GOS can help restore gut health after antibiotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the effects of galacto-oligosaccharides on the gut microbiota of healthy adults receiving amoxicillin treatment. Ladirat, SE., Schoterman, MH., Rahaoui, H., et al.[2014]

Galactooligosaccharides (GOS) significantly increased the growth of beneficial Lactobacillus strains in both piglets and mice, which helped alleviate Salmonella infections, indicating their potential as a prebiotic for gut health.

Different Lactobacillus strains showed unique protective mechanisms: L. delbrueckii reduced intestinal inflammation by inhibiting specific signaling pathways, while L. johnsonii prevented Salmonella from adhering to gut cells, highlighting the varied roles of GOS-enriched probiotics in intestinal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strain specificity of lactobacilli with promoted colonization by galactooligosaccharides administration in protecting intestinal barriers during Salmonella infection. Wu, Y., Zhang, X., Liu, X., et al.[2023]

The combination of prebiotic galacto-oligosaccharides (GOS) and inulin significantly reduced the formation of aberrant crypt foci (ACF) by 55.8% in a rodent model of colorectal cancer, indicating a strong preventive effect against cancer development.

This study suggests that the novel combination of GOS and inulin is more effective than either treatment alone, enhancing short-chain fatty acid production and bacterial enzymatic activities, which may contribute to its chemopreventive properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Combination of Prebiotics Galacto-Oligosaccharides and Inulin-Inhibited Aberrant Crypt Foci Formation and Biomarkers of Colon Cancer in Wistar Rats. Qamar, TR., Syed, F., Nasir, M., et al.[2018]

The study involving 365 healthy infants showed that feeding a galactooligosaccharides (GOS)-containing formula resulted in significant prebiotic effects, such as changes in faecal composition, increased Bifidobacterium counts, and improved stool consistency and frequency by 4 months of age.

Despite these positive changes in gut health, the GOS-containing formula did not lead to a reduction in the incidence of infections or allergic manifestations during the first year of life, indicating that while GOS may benefit gut microbiota, it does not necessarily prevent illness or allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prebiotic effect during the first year of life in healthy infants fed formula containing GOS as the only prebiotic: a multicentre, randomised, double-blind and placebo-controlled trial. Sierra, C., Bernal, MJ., Blasco, J., et al.[2022]

Galactooligosaccharides (GOS) are effective prebiotics that promote gut health by selectively stimulating beneficial probiotics and inhibiting harmful bacteria, leading to various health benefits including improved gastrointestinal and metabolic health.

GOS are safe, stable, and versatile food additives that enhance the sensory and nutritional qualities of food products, making them a valuable ingredient in the food industry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galactooligosaccharides: Synthesis, metabolism, bioactivities and food applications. Wang, K., Duan, F., Sun, T., et al.[2023]

Lactose-derived prebiotics, confirmed as safe by the FDA, are effective in promoting gastrointestinal health by supporting beneficial gut microflora and are recommended by medical practitioners in various forms, including dairy products and fruit juices.

Clinical studies show that galacto-oligosaccharides can reduce the risk of different types of diarrhea, while lactulose and lactosucrose are effective in preventing inflammatory bowel diseases and reducing the risk of hepatic encephalopathy, making them valuable therapeutic options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological Activities of Lactose-Derived Prebiotics and Symbiotic with Probiotics on Gastrointestinal System. Nath, A., Haktanirlar, G., Varga, Á., et al.[2019]

A new GOS product, SK-GOS, was developed to be hypoallergenic and safer than the previously known GOS product (Bc-GOS), which caused allergic reactions in some individuals.

The study identified specific sugar chain derivatives in Bc-GOS responsible for allergic reactions, allowing researchers to create SK-GOS using different enzyme sources that do not trigger these allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of hypoallergenic galacto-oligosaccharides on the basis of allergen analysis. Kaneko, K., Watanabe, Y., Kimura, K., et al.[2014]

A study on Sprague Dawley rats showed that galacto-oligosaccharide (GOS) administered at doses up to 2000 mg/kg/day for 10 weeks did not cause any toxic effects or abnormal reproductive functions in either male or female rats.

The growth and development of offspring were normal, with no observed malformations or differences in birth weight, indicating that GOS is safe for reproductive health at high doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A one-generation reproduction toxicity study in rats treated orally with a novel galacto-oligosaccharide. Kobayashi, T., Takano, M., Kaneko, K., et al.[2015]

In a rodent model of colorectal cancer, novel galacto-oligosaccharides (GalOS) significantly reduced the formation of aberrant crypt foci (ACF) by 27.3% compared to controls, indicating their potential protective role against cancer development.

GalOS treatment also improved gut health by increasing beneficial bacteria populations and short-chain fatty acids (SCFA) levels, while reducing harmful bacterial enzymatic activities, suggesting a multifaceted mechanism of action in cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Novel Prebiotic Galacto-Oligosaccharides on Various Biomarkers of Colorectal Cancer in Wister Rats. Qamar, TR., Iqbal, S., Syed, F., et al.[2018]

Galacto-oligosaccharides (GOS) are confirmed as effective prebiotics, with ongoing research focused on improving their production for higher purity and efficiency, utilizing glycoside hydrolases (GH) to convert lactose.

The composition of GOS mixtures affects their prebiotic activity and physiological effects, highlighting the importance of enzyme selection in the production process to optimize health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Galacto-Oligosaccharides: Production, Properties, Applications, and Significance as Prebiotics. Torres, DPM., Gonçalves, MDPF., Teixeira, JA., et al.[2021]

A new method using porous graphitic carbon liquid chromatography and orbitrap tandem mass spectrometry successfully characterized 68 different galacto-oligosaccharides (GOS), which is crucial for ensuring the quality and efficacy of prebiotic supplements.

The study found that 15 major GOS components with degrees of polymerization (DP) between 2 and 5 made up over 65% of the total GOS content, highlighting significant variability in GOS profiles across different batches and sources, which can impact their prebiotic effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile diversity of galacto-oligosaccharides from disaccharides to hexasaccharides by porous graphitic carbon liquid chromatography-orbitrap tandem mass spectrometry. Lin, CC., Yang, YC., Lu, ZY., et al.[2022]

Oligosaccharides, such as inulin and fructo-oligosaccharides, are gaining attention as prebiotic ingredients that can improve gut health and may help with conditions like colon cancer and inflammatory bowel disease.

While there is promising evidence from in vitro and in vivo studies, more large-scale human trials are needed to fully understand the efficacy and mechanisms of these prebiotics in promoting gut health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional oligosaccharides: application and manufacture. Rastall, RA.[2011]

In a study involving 18 healthy adults over 12 weeks, the prebiotic galactooligosaccharide (GOS) significantly increased the abundance of beneficial bifidobacteria in the gut microbiota, with some individuals experiencing five- to ten-fold increases.

The effects of GOS were specific and varied among individuals, leading to a decrease in Bacteroides bacteria, and were influenced by the dosage of GOS consumed, indicating that GOS selectively promotes certain beneficial bacteria while altering the overall gut microbiome composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans. Davis, LM., Martínez, I., Walter, J., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Short-term effect of prebiotics administration on stool characteristics and serum cytokines dynamics in very young children with acute diarrhea. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Exploring the effects of galacto-oligosaccharides on the gut microbiota of healthy adults receiving amoxicillin treatment. [2014]

3. Egypt pubmed.ncbi.nlm.nih.gov

Strain specificity of lactobacilli with promoted colonization by galactooligosaccharides administration in protecting intestinal barriers during Salmonella infection. [2023]

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

Novel Combination of Prebiotics Galacto-Oligosaccharides and Inulin-Inhibited Aberrant Crypt Foci Formation and Biomarkers of Colon Cancer in Wistar Rats. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Prebiotic effect during the first year of life in healthy infants fed formula containing GOS as the only prebiotic: a multicentre, randomised, double-blind and placebo-controlled trial. [2022]

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

Galactooligosaccharides: Synthesis, metabolism, bioactivities and food applications. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Biological Activities of Lactose-Derived Prebiotics and Symbiotic with Probiotics on Gastrointestinal System. [2019]

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

Development of hypoallergenic galacto-oligosaccharides on the basis of allergen analysis. [2014]

9. England pubmed.ncbi.nlm.nih.gov

A one-generation reproduction toxicity study in rats treated orally with a novel galacto-oligosaccharide. [2015]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Novel Prebiotic Galacto-Oligosaccharides on Various Biomarkers of Colorectal Cancer in Wister Rats. [2018]

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

Galacto-Oligosaccharides: Production, Properties, Applications, and Significance as Prebiotics. [2021]

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

Profile diversity of galacto-oligosaccharides from disaccharides to hexasaccharides by porous graphitic carbon liquid chromatography-orbitrap tandem mass spectrometry. [2022]

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

Functional oligosaccharides: application and manufacture. [2011]

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

Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans. [2021]