Prebiotic Galacto-oligosaccharide and Acute GVHD

NCT ID: NCT04373057

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-22
• Study Completion Date: 2028-02-01

Brief Summary

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.

Detailed Description

Humans carry on the order of 100 trillion microbial cells (the microbiota),which play a major role in normal health as well as disease pathogenesis. In the gut, the microbiota interact with the intestinal epithelium and immune system to regulate inflammation and metabolism. The impact of the microbiota on GVHD and other clinical outcomes may be mediated by bacterial metabolites such as short chain fatty acid (SCFAs). In particular, the SCFA butyrate has been shown to be a preferred fuel source of human colonic epithelial cells and essential for normal differentiation of regulatory immune cells in the intestine, which in turn may decrease GVHD. This is supported by murine studies, in which manipulating the gut microbiota to increase microbial SCFA production or by direct administration (oral gavage) of butyrate has been shown to improve HCT outcomes, including protection from GVHD

Manipulating the gut microbiota in HCT to decrease the risk of GVHD could potentially be done using several methods, namely prebiotics (dietary carbohydrates or fibers), probiotics (live bacteria), and fecal transplantation. In contrast to live bacteria, prebiotics are dietary carbohydrates classified as nutritional supplements that can sustain gut bacteria, regulate gastrointestinal transit time, and foster cooperative metabolic networks between enteric microbes. Because prebiotics encourage the growth of existing bacteria rather than introducing new organisms, they may be safer. Moreover, bacterial fermentation of prebiotics may yield SCFA.

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, three dose levels 0.75g/day (25% maximum dose, D1), 1.5g/day (50% maximum dose D2), and 2.9g/day (maximum dose, D3) will be evaluated to find out the provisional maximum tolerated dose (pMTD) of GOS to be used in phase 2. In phase 2, using pMTD 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. Note that if the pMTD is D3, there will be a D1 and D2 lead-in period similar to the Phase 1 study however if the pMTD is D2, there will only be a lead-in with D1 and if pMTD is D1, there will only be one dose with no lead-in. The study will generate important data on gut microbiota responses to help tailor or personalize future prebiotic therapies to patients and their microbiota.

Conditions

Acute GVHD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Galacto-oligosaccharide

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 Type: EXPERIMENTAL

Galacto-oligosaccharide

Intervention Type: DIETARY_SUPPLEMENT

GOS will be administered at determined dose levels per protocol once daily from about 30 days before transplant to about 4 weeks after transplant.

Maltodextrin

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.

Group Type: PLACEBO_COMPARATOR

Maltodextrin

Intervention Type: DIETARY_SUPPLEMENT

Maltodextrin will be administered at comparable dose level as GOS (in Phase II) once daily from about 30 days before transplant to about 4 weeks after transplant.

Interventions

Galacto-oligosaccharide

GOS will be administered at determined dose levels per protocol once daily from about 30 days before transplant to about 4 weeks after transplant.

Intervention Type: DIETARY_SUPPLEMENT

Maltodextrin

Maltodextrin will be administered at comparable dose level as GOS (in Phase II) once daily from about 30 days before transplant to about 4 weeks after transplant.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Bimuno®, B-GOS

Eligibility Criteria

Inclusion Criteria

• Plan to undergo allogeneic HCT for any cancer or non-cancer illness
• Age 18-80 years
• Karnofsky Performance Status >70

Exclusion Criteria

• Pregnant/lactating
• Malabsorption syndrome, short bowel or chologenic diarrhea
• At time of enrollment, Grade 2 or higher GI symptoms per NCI-CTCAE
• Active treatment with other prebiotics, probiotics, or herbal supplementation (ok if stops before enrollment)
• Active treatment with antibiotics (with the exception of prophylactic antibiotics)
• Concurrent enrollment on the Duke HCT Home Transplant study or another clinical trial targeting GVHD; patients who are enrolled in observational or non-pharmacologic intervention trials (for example, the Duke HCT Research-POP Pre and Peri-HCT Optimization Program aka "R-POP") or pharmacologic or cellular therapy trials with other targets (for example, NK DLI) are NOT excluded

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mitchell Horwitz, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Health

Anthony Sung, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kansas

Locations

Kansas University Medical Center

Kansas City, Kansas, United States

Site Status: RECRUITING

Duke

Durham, North Carolina, United States

Site Status: ACTIVE_NOT_RECRUITING

Countries

United States

Central Contacts

Andrea Pires

Role: CONTACT

andrea.pires@duke.edu

9196684978

Lauren Hill

Role: CONTACT

lauren.hill@duke.edu

9196682369

Facility Contacts

Anthony Sung, MD

Role: primary

References

Lakshmanan AP, Deola S, Terranegra A. The Promise of Precision Nutrition for Modulation of the Gut Microbiota as a Novel Therapeutic Approach to Acute Graft-versus-host Disease. Transplantation. 2023 Dec 1;107(12):2497-2509. doi: 10.1097/TP.0000000000004629. Epub 2023 May 16.

Reference Type: DERIVED

PMID: 37189240 (View on PubMed)

Other Identifiers

Pro00105137

Identifier Type: -

Identifier Source: org_study_id