Prebiotics for Multiple Myeloma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Christopher R D'Angelo, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Nebraska

Disqualifiers: Bariatric surgery, Chronic gastrointestinal disease, others

Trial Summary

What is the purpose of this trial?

Higher gut microbiome diversity has been associated with improved survival following autologous stem cell transplantation in multiple myeloma and lymphoma. This study hypothesises that prebiotic supplementation with resistant starch (RS) will improve gut microbiome diversity at time of stem cell engraftment. To test this, participants will either have RS or a placebo (maltodextrin) mixed into a food item of their choice for approximately 10 days prior to stem cell infusion and continue to the first day of neutrophil engraftment. The study will look at the difference in gut microbiome diversity between the RS and placebo arm collected at the engraftment timepoint, dietary evaluation to assess the impact of subject diet on microbiome response to intervention and serum sample collection to assess differences to gut permeability during transplant.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment Maltodextrin, Maltodextrin powder, Dextrin, Maltodextrin DE, Resistant Starch, Resistant Potato Starch, RS, RPS for Multiple Myeloma?

Research on prebiotics like resistant starch shows they can positively affect gut bacteria and may help in cancer prevention, particularly colorectal cancer, by reducing harmful cell growth and promoting the death of damaged cells. While this is not directly related to multiple myeloma, it suggests potential benefits of prebiotics in cancer-related treatments. ^{1 2 3 4 5}

Is resistant starch safe for human consumption?

Resistant starch, a type of prebiotic, is generally considered safe for human consumption. Studies show it can increase stool bulk and promote healthy gut bacteria without significant adverse effects. ^{2 3 6 7 8}

How does the treatment Resistant Starch differ from other treatments for Multiple Myeloma?

Resistant Starch (RS) is unique because it works by altering the gut microbiome, which can lead to changes in metabolic functions and immune responses. Unlike traditional treatments for Multiple Myeloma that directly target cancer cells, RS aims to improve health by promoting beneficial gut bacteria and increasing short-chain fatty acids, which may have indirect effects on cancer progression. ^{2 3 9 10 11}

Research Team

Christopher R D'Angelo, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

This trial is for adults over 19 with multiple myeloma or certain types of lymphoma who are about to have their first stem cell transplant. They must be willing to follow the study rules and provide informed consent. People can't join if they've had issues with fiber supplements, won't give stool samples, have a history of major gut surgery or chronic gut diseases, or allergies to potato starch or maltodextrin.

Inclusion Criteria

I am 19 years old or older.

I have been diagnosed with multiple myeloma, Non-Hodgkin lymphoma, or Hodgkin lymphoma.

Willing to provide informed consent

Exclusion Criteria

Not suitable for study participation due to other reasons at the discretion of the investigators

I have had weight loss surgery or suffer from a long-term gut condition.

You had a bad reaction to taking fiber supplements before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants receive prebiotic supplementation with resistant starch or placebo for approximately 10 days prior to stem cell infusion

10 days

1 visit (in-person) for enrollment

Treatment

Participants continue prebiotic supplementation until the first day of neutrophil engraftment

Approximately 30 days

4 visits (in-person) for fecal sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 weeks

Treatment Details

Interventions

• Maltodextrin (Behavioural Intervention)
• Resistant Starch (Prebiotic)

Trial Overview The study tests whether adding resistant starch (RS) to food improves gut microbiome diversity in patients receiving stem cell transplants compared to a placebo (maltodextrin). Participants will consume RS or placebo from around 10 days before until the day their new white blood cells start growing after the transplant.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

resistant starch

Group II: Placebo Placebo Group 1 Intervention

maltodextrin

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Michael Dixon

University of Nebraska

Chief Executive Officer since 2010

PhD in Molecular Biology

Dr. Makker

University of Nebraska

Chief Medical Officer since 2020

MD from University of Nebraska Medical School

Findings from Research

Inulin, a prebiotic, was found to significantly reduce harmful coliform bacteria and increase beneficial lactobacilli in the gut of rats, suggesting it can positively alter gut microbiota during colon cancer development.

The study showed that inulin supplementation decreased markers associated with inflammation and cancer progression, such as COX-2 and NFκB, indicating its potential as a chemopreventive agent against colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes chemopreventive markers in colorectal cancer development after inulin supplementation. Hijova, E., Szabadosova, V., Strojny, L., et al.[2023]

Resistant starch (both RS2 and RS3) significantly improved the colon flora in mice by increasing beneficial bifidobacteria and decreasing harmful enterobacteria, indicating a positive effect on gut health.

The intake of RS2, particularly at higher concentrations, led to increased production of short-chain fatty acids (SCFAs) and a reduction in the pH of feces and cecum content, suggesting enhanced fermentation and overall digestive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Influence of resistant starch on colon flora of rats]. He, M., Hong, J., Yang, YX., et al.[2005]

The prebiotic xylan-stearic acid conjugate (SCXN) effectively delivers the chemotherapy drug capecitabine (Cap) in a colorectal cancer mouse model, significantly increasing the drug's concentration in tumors and enhancing its therapeutic effects.

SCXN not only improves the anti-tumor immunity and increases the tumor inhibition rate from 5.29% to 71.78%, but also extends the median survival time of CRC mice from 14 to 33.5 days, demonstrating its potential as a promising treatment strategy that combines gut microbiota modulation with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining gut microbiota modulation and chemotherapy by capecitabine-loaded prebiotic nanoparticle improves colorectal cancer therapy. Lang, T., Zhu, R., Zhu, X., et al.[2023]

Fermentation supernatant fractions of inulin significantly increased short-chain fatty acids (SCFA) and decreased harmful bile acids, showing potential protective effects against colorectal cancer.

In human colon cell lines, particularly in early-stage cancer cells (LT97), the fermentation supernatant induced apoptosis and inhibited cell growth, suggesting that prebiotic fibers like inulin could play a role in cancer chemoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fermentation products of inulin-type fructans reduce proliferation and induce apoptosis in human colon tumour cells of different stages of carcinogenesis. Munjal, U., Glei, M., Pool-Zobel, BL., et al.[2022]

Epidemiological studies suggest that resistant starch (RS) may provide a protective effect against colorectal cancer (CRC), with an estimated protection magnitude of 25-50%, although the measurement tools for RS consumption are not well-developed.

Human intervention studies indicate that RS consumption leads to beneficial changes in colonic biology, such as increased stool bulk and production of short-chain fatty acids, which may enhance colonic health and facilitate the removal of genetically damaged cells, potentially lowering CRC risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistant starch and colorectal neoplasia. Young, GP., Le Leu, RK.[2019]

Resistant starch (RS) is important for health because it produces butyrate in the colon, which can positively affect cell metabolism and may help inhibit the growth of colon tumors.

There is ongoing debate about how to accurately measure RS in foods, as some methods may not capture all resistant starch types, highlighting the need for better analytical techniques and clearer food labeling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in dietary fibre characterisation. 2. Consumption, chemistry, physiology and measurement of resistant starch; implications for health and food labelling. Champ, M., Langkilde, AM., Brouns, F., et al.[2008]

In a study involving 24 healthy men, supplementing their diet with 32 g of resistant starch (RS) daily for 4 weeks increased stool weight and colonic fermentative activity compared to glucose, indicating some positive digestive effects.

However, the resistant starch supplements (RS2 and RS3) did not significantly alter other potential risk factors for colon cancer, such as fecal pH, short-chain fatty acid concentrations, or bile acid levels, suggesting limited impact on colon cancer risk in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited effect of consumption of uncooked (RS2) or retrograded (RS3) resistant starch on putative risk factors for colon cancer in healthy men. Heijnen, ML., van Amelsvoort, JM., Deurenberg, P., et al.[2018]

A diet enriched with resistant starch type 4 (RS4) significantly improved metabolic health markers in 20 individuals with metabolic syndrome, leading to lower cholesterol, fasting glucose, and body fat compared to a control group.

The RS4 diet altered gut microbiota composition, increasing beneficial bacteria and short-chain fatty acids (SCFAs) like butyrate and propionate, which are linked to improved metabolic functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of dietary resistant starch type 4 on human gut microbiota and immunometabolic functions. Upadhyaya, B., McCormack, L., Fardin-Kia, AR., et al.[2022]

Two novel strains of lactic acid bacteria, identified as Bifidobacterium adolescentis, were isolated from human fecal samples for their ability to utilize resistant starch (RS3), indicating their potential as probiotics.

The strain B. adolescentis JSC2 was found to be safe for human use, as it tested negative for β-glucuronidase and showed tolerance to acidic and bile-salt environments, suggesting it could be beneficial for human health and the food industry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening and selection of Bifidobacterium strains isolated from human feces capable of utilizing resistant starch. Kim, HJ., Shin, SI., Lee, SJ., et al.[2018]

A study involving healthy humans demonstrated that different types of resistant starches (RS4s) can specifically alter gut microbiome composition and metabolic activity, particularly influencing the production of beneficial short-chain fatty acids like propionate and butyrate.

The effects of these resistant starches were consistent and dose-dependent, plateauing at 35 g/day, suggesting that precise dietary fiber structures can be used to target and manipulate gut health effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision Microbiome Modulation with Discrete Dietary Fiber Structures Directs Short-Chain Fatty Acid Production. Deehan, EC., Yang, C., Perez-Muñoz, ME., et al.[2020]

References

1. Slovakia pubmed.ncbi.nlm.nih.gov

Changes chemopreventive markers in colorectal cancer development after inulin supplementation. [2023]

2. China pubmed.ncbi.nlm.nih.gov

[Influence of resistant starch on colon flora of rats]. [2005]

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

A synbiotic combination of resistant starch and Bifidobacterium lactis facilitates apoptotic deletion of carcinogen-damaged cells in rat colon. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Combining gut microbiota modulation and chemotherapy by capecitabine-loaded prebiotic nanoparticle improves colorectal cancer therapy. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Fermentation products of inulin-type fructans reduce proliferation and induce apoptosis in human colon tumour cells of different stages of carcinogenesis. [2022]

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

Resistant starch and colorectal neoplasia. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Advances in dietary fibre characterisation. 2. Consumption, chemistry, physiology and measurement of resistant starch; implications for health and food labelling. [2008]

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

Limited effect of consumption of uncooked (RS2) or retrograded (RS3) resistant starch on putative risk factors for colon cancer in healthy men. [2018]

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

Impact of dietary resistant starch type 4 on human gut microbiota and immunometabolic functions. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Screening and selection of Bifidobacterium strains isolated from human feces capable of utilizing resistant starch. [2018]

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

Precision Microbiome Modulation with Discrete Dietary Fiber Structures Directs Short-Chain Fatty Acid Production. [2020]