Prebiotic Supplement for Acute GVHD

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether a dietary supplement called galacto-oligosaccharide (GOS) can prevent graft-versus-host disease (GVHD), a condition that can occur after stem cell transplants. In the first phase, researchers will determine the optimal dose of GOS. In the second phase, participants will receive either GOS or a placebo to evaluate GOS's effectiveness. The trial seeks individuals planning to undergo a stem cell transplant for any illness and who have a good performance status, meaning they can manage daily activities well. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking medical research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that galacto-oligosaccharide (GOS), a type of prebiotic supplement, is generally safe for people. Studies have found that GOS can reduce the severity of graft-versus-host disease (GVHD) in mice, indicating potential use in humans. Prebiotics like GOS are usually safe and offer benefits, such as improved gut health.

Research has reported no major side effects for GOS, suggesting it is likely safe for people, especially as it undergoes early-phase trials. These trials aim to determine the best dose and closely monitor any side effects. If GOS were already approved for another condition, it would further support its safety, but current evidence is still being gathered.

Overall, early studies on GOS suggest it is a safe option for those considering participation in clinical trials. Participants can expect careful monitoring to ensure their safety throughout the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Galacto-oligosaccharide (GOS) for acute GVHD because, unlike traditional treatments like steroids and immunosuppressive drugs, GOS is a prebiotic. This means it works by nurturing beneficial gut bacteria, which might help modulate the immune response without the heavy side effects associated with current options. Additionally, GOS is administered orally, making it easier and potentially more comfortable for patients compared to some standard treatments. This novel approach could lead to a more natural and less invasive way to manage acute GVHD symptoms.

What evidence suggests that this prebiotic supplement could be effective for preventing acute GVHD?

Research has shown that galacto-oligosaccharides (GOS), which participants in this trial may receive, might reduce the severity of graft-versus-host disease (GVHD) by promoting the growth of beneficial gut bacteria. Studies in mice found that adding GOS led to less severe GVHD, suggesting that GOS might protect the gut lining, which is crucial for managing GVHD. By altering the balance of gut bacteria, GOS could offer a promising approach to preventing or reducing GVHD after stem cell transplants. Early results are promising, but further research is needed to confirm these effects in humans. ^{1 4 6 7 8}

Who Is on the Research Team?

Anthony Sung, MD

Principal Investigator

University of Kansas

Mitchell Horwitz, MD

Principal Investigator

Duke Health

Are You a Good Fit for This Trial?

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10653043/

Prebiotic galactooligosaccharides interact with mouse gut ... Rather, GOS supplementation was linked to decreased GVHD severity, despite mice consuming GOS ad libitum (supplemental Methods), which could have contributed to ...

2. trial.medpath.com trial.medpath.com/clinical-trial/3a2b83ae480dd192/nct04373057-phase-i-ii-trial-prebiotic-galacto-oligosaccharide-prevent-acute-gvhd

Prebiotic Galacto-oligosaccharide and Acute GVHD | MedPath The purpose of this study is to determine whether the carbohydrate prebiotic (dietary supplement) known as galacto-oligosaccharide (GOS) can modulate the ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-04340

Prebiotic Galacto-Oligosaccharides for the Prevention of ... This phase I/II study tests the safety, best dose, and effectiveness of galacto-oligosaccharide prebiotic supplements (GOS) in preventing graft versus host ...

4. withpower.com withpower.com/trial/phase-2-2021-845e9

Prebiotic Supplement 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 ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04373057/prebiotic-galacto-oligosaccharide-and-acute-gvhd

Prebiotic Galacto-oligosaccharide and Acute GVHD The purpose of this study is to determine whether the carbohydrate prebiotic (dietary supplement) known as galacto-oligosaccharide (GOS) can ...

6. ashpublications.org ashpublications.org/blood/article-abstract/140/21/2300/486126/Prebiotic-galactooligosaccharides-interact-with?redirectedFrom=fulltext

Prebiotic galactooligosaccharides interact with mouse gut ... GVHD is associated with microbiota disruptions, which occur with prophylactic antibiotic therapy, chemotherapy, and radiation given as part of ...

7. gvhdhub.com gvhdhub.com/medical-information/nutritional-interventions-in-acute-gvhd

Nutritional interventions in acute GvHD Prebiotics may be safer to recommend as galacto-oligosaccharides are associated with an increase in short-chain fatty acid and butyrate ...

8. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06797-5

The microbiome in graft-versus-host disease: a tale of two ... The intestinal microbiota exerts a profound influence on the development and severity of acute GVHD by shaping the host's immune environment ...