SCFA Supplementation for Radiation Poisoning

Recruiting at 1 trial location

Overseen By Flora Danquah

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Histone deacetylase inhibitors

Disqualifiers: Pregnancy, Prior RT, IBD, others

Compensation: Varies

Number of Visits: 1

122 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a supplement called SCFA (Short-Chain Fatty Acid Supplementation) can reduce stomach and intestine problems caused by radiation therapy, a common treatment for certain cancers. It compares SCFA's effects with a placebo to determine if SCFA is a safe and affordable option. Eligible participants include those who have undergone certain cancer treatments and have not received radiation to the stomach area before. Participants must be receiving radiation therapy to the abdominal or pelvic area. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you cannot be on certain prohibited medications or treatments listed in section 5.6 of the protocol. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Research has shown that short-chain fatty acids (SCFAs) might be safe for people. Studies suggest SCFAs could help reduce inflammation in the intestines caused by chemotherapy or radiation. This is important for those receiving radiation treatment, as it may lessen gut-related side effects.

Previous reports indicate that SCFAs are linked to a lower risk of allergic reactions and colitis, which is inflammation of the colon. These findings suggest SCFAs might be well-tolerated and could offer protective benefits.

However, since this treatment is still in early testing, its safety is not fully confirmed. Early trials focus heavily on safety and are closely monitored. If SCFAs were found to be unsafe, the trials would stop. So far, no strong evidence of serious side effects from SCFAs in humans has emerged. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for radiation poisoning, which often focus on reducing symptoms and managing damage after exposure, SCFA supplementation offers a proactive approach by potentially enhancing the body's natural resilience to radiation. Short Chain Fatty Acids (SCFAs) are promising because they may help fortify the gut lining and reduce inflammation, offering a protective effect that current treatments don't address. Researchers are excited about this approach because it targets the root of radiation damage, aiming to prevent it before it occurs, rather than just treating the aftermath.

What evidence suggests that SCFA Supplementation might be an effective treatment for radiation poisoning?

Research has shown that short-chain fatty acids (SCFAs) might protect healthy tissues from radiation's harmful effects. Studies indicate that SCFAs can boost the immune system and may reduce damage from radiation therapy. In this trial, one group of participants will receive SCFA supplementation, which has shown promise in protecting the intestines when radiation exposure lowers SCFAs. Another group will receive a placebo. Other research suggests that SCFAs might also reduce the risk of lung injury from radiation. These findings highlight a promising role for SCFAs in lessening radiation side effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Shivani Sud, MD

Principal Investigator

UNC

Are You a Good Fit for This Trial?

Adults over 18 with GI, urologic or gynecologic cancers needing abdominopelvic radiation can join. They should be fairly healthy, have an ECOG score ≤2, and could've had prior chemo or surgery. Women must use contraception; men with partners of childbearing potential must do the same or be vasectomized.

Inclusion Criteria

I have a confirmed GI, urologic, or gynecologic cancer and will receive radiation of at least 40Gy to my abdomen or pelvis.

Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. Consent for the use of any residual material from biopsy and/or surgical resection (archival tissue) and serial blood draws will be required for enrollment.

I finished my last cancer treatment 14 days ago and have recovered from its side effects.

Exclusion Criteria

I am not taking any medications or treatments that are not allowed in this study.

I am currently taking vorinostat.

I have had radiation therapy to my abdomen or pelvis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants begin taking SCFA or placebo 1 week prior to starting radiation therapy

1 week

1 visit (in-person)

Radiation Therapy

Participants receive abdominopelvic radiation therapy while continuing SCFA or placebo

Duration of radiation therapy

Weekly visits (in-person)

Post-treatment

Participants continue taking SCFA or placebo for 1 week after completing radiation therapy

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments up to 5 years post RT

5 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• SCFA Supplementation

Trial Overview This study tests if SCFA supplementation reduces gastrointestinal toxicity from radiation therapy compared to a placebo (tapioca flour). Participants are randomly assigned to either the SCFA group or the placebo group to see which is more effective.

How Is the Trial Designed?

Group I: Short Chain Fatty Acid (SCFA) Active Control 1 Intervention

4-6 grams of powder mixed with food and taken everyday starting 1 week prior-1 week post Radiation Therapy.

Group II: Placebo (Tapioca) Placebo Group 1 Intervention

5 grams taken everyday starting 1 week prior-1 week post Radiation Therapy.

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Published Research Related to This Trial

In a study involving rats with induced chronic colitis, butyrate enemas significantly improved clinical symptoms, reduced inflammation, and restored sodium absorption in the colon compared to untreated and saline-treated groups.

The treatment led to a decrease in colonic damage scores and tissue myeloperoxidase activity, indicating effective colonic repair and recovery of normal function after butyrate administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Butyrate enema therapy stimulates mucosal repair in experimental colitis in the rat. Butzner, JD., Parmar, R., Bell, CJ., et al.[2019]

Short chain fatty acids (SCFAs) like acetate, propionate, and butyrate are crucial for gut health and metabolic functions, as they help maintain gut integrity and regulate various metabolic processes such as appetite and glucose levels.

While animal studies suggest that increasing SCFA production can prevent gastrointestinal issues, obesity, and type 2 diabetes, there is a significant need for well-controlled human studies to confirm these benefits and understand the factors influencing SCFA production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short chain fatty acids in human gut and metabolic health. Blaak, EE., Canfora, EE., Theis, S., et al.[2021]

In a study of 140 ICU patients with severe systemic inflammatory response syndrome (SIRS), fecal concentrations of short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate were significantly lower than those in healthy volunteers, indicating a potential disruption in gut health during critical illness.

The low levels of SCFAs persisted throughout the 6-week ICU stay and were associated with gastrointestinal complications, suggesting that maintaining SCFA levels could be a therapeutic strategy to prevent such complications in critically ill patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid and Sustained Long-Term Decrease of Fecal Short-Chain Fatty Acids in Critically Ill Patients With Systemic Inflammatory Response Syndrome. Yamada, T., Shimizu, K., Ogura, H., et al.[2019]

Acute radiation-induced intestinal injury (RIII) leads to significant changes in gut microbiota, with specific bacterial populations correlating with radiation dose, particularly at the critical stage of injury (3.5 days post-radiation).

Administering probiotics for 14 days after exposure to radiation improved survival and helped alleviate intestinal damage, indicating that probiotics could be an effective strategy to mitigate the effects of acute RIII and restore gut microbiota diversity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dysbiosis of Gut Microbiota Is Associated With the Progression of Radiation-Induced Intestinal Injury and Is Alleviated by Oral Compound Probiotics in Mouse Model. Zhao, TS., Xie, LW., Cai, S., et al.[2021]

In a study with adult female Sprague-Dawley rats, a diet high in saturated fatty acids (S) showed potential protective effects against intestinal damage from abdominal radiation, compared to a diet high in polyunsaturated fatty acids (P).

Irradiated rats on the saturated diet had better uptake of glucose and maintained lipid absorption, suggesting that a saturated fatty acid diet may help mitigate the negative effects of radiation on intestinal function, warranting further research in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saturated fatty acid diet prevents radiation-associated decline in intestinal uptake. Thomson, AB., Keelan, M., Lam, T., et al.[2017]

In a study involving 19 patients with chronic radiation proctitis, short chain fatty acid enemas significantly reduced rectal bleeding and improved endoscopic scores after five weeks of treatment.

While short chain fatty acid enemas showed initial benefits in healing, continuous treatment is necessary for sustained improvement, as differences between treatment and placebo groups diminished after six months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short chain fatty acids are effective in short-term treatment of chronic radiation proctitis: randomized, double-blind, controlled trial. Pinto, A., Fidalgo, P., Cravo, M., et al.[2019]

Radiotherapy causes metabolic changes in cancer patients, leading to the loss of important intracellular elements like potassium and nitrogen, while increasing extracellular sodium and water retention.

Providing adequate parenteral nutrition with high-calorie fat emulsions and easily absorbed amino acids can help correct these metabolic imbalances during radiation treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Parenteral feeding during radiotherapy of oncological patients]. Ruderman, AI., Sudzhian, AV.[2015]

In a study with Swiss mice, oral administration of short-chain fatty acids (SCFA) significantly reduced intestinal damage caused by the chemotherapy drug Ara-C, indicating a protective effect against inflammation and necrosis.

SCFA treatment led to higher protein and nucleotide levels in the intestinal mucosa and increased the height of intestinal villi, suggesting that SCFA may improve gut health during cancer treatment-related mucositis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral administration of short-chain fatty acids reduces the intestinal mucositis caused by treatment with Ara-C in mice fed commercial or elemental diets. Ramos, MG., Bambirra, EA., Cara, DC., et al.[2013]

In a pilot study involving seven patients, the use of short-chain fatty acid (SCFA) enemas for four weeks led to clinical improvement in all participants suffering from radiation proctitis.

While SCFA enemas showed clinical benefits, the changes observed in endoscopic and pathological parameters were modest and not statistically significant, suggesting further research is needed to fully understand their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis. al-Sabbagh, R., Sinicrope, FA., Sellin, JH., et al.[2004]

Short chain fatty acids (SCFAs), particularly butyrate, have shown potential in treating inflammatory bowel disease and colon cancer due to their ability to induce cell cycle arrest and apoptosis.

Recent genomic and proteomic analyses have enhanced our understanding of SCFAs' mechanisms of action, highlighting their role in protein synthesis and differentiation, which could lead to new therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular and physiological effects of short-chain fatty acids. Miller, SJ.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9612155/

Gut Microbiota-Derived Short-Chain Fatty Acids A body of evidence is developing that SCFAs may have a role in the efficacy of various cancer treatment types, including chemotherapy, immunotherapy, and ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0003986124002947

The role of short-chain fatty acids in cancer prevention and ... SCFAs may protect the normal tissues against the damaging effects of radiation. The effectiveness of radiotherapy can be altered by microbial metabolites ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8300561/

Review: Effect of Gut Microbiota and Its Metabolite SCFAs ... In radiation-induced intestinal injury, SCFAs decreased, but dietary pectin could reverse and increase SCFAs so as to play a protective role in ...

4. redjournal.org redjournal.org/article/S0360-3016(24)01703-6/fulltext

Short Chain Fatty Acids for Prevention and Treatment ... SCFAs can effectively regulate body immunity, and exogenous SCFAs supplementation is an effective way to reduce the incidence of radiation lung injury.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04700527?tab=table

NCT04700527 | The Effects of SCFA Supplementation in ... The purpose of this study is to assess and compare GI toxicity from RT between subjects who receive therapeutic SCFA and those who receive placebo, in hopes of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12484129/

Single radiation exposure induces gut microbiota dysbiosis ... We aimed to investigate the effects of single and fractionated radiation exposures on gut microbiota diversity and short-chain fatty acid (SCFA) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7716145/

The protective role of short-chain fatty acids acting as ... This review suggests the therapeutic potential of SCFAs for the management of chemotherapy- or radiation-induced intestinal inflammation. Keywords: Short-chain ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223010673

The impact of microbiota-derived short-chain fatty acids on ... Consumption of fiber-rich foods and SCFAs has been associated with a reduced risk of allergic diseases and colitis, although therapeutic outcomes may vary.

9. mdpi.com mdpi.com/1422-0067/25/20/10879

Therapeutic and Immunologic Effects of Short-Chain Fatty ... The results showed a significant reduction in the total amount of short-chain fatty acids and butyrate during a flare in the patients treated with mesalamine, ...

10. researchforme.unc.edu researchforme.unc.edu/study-details?rcid=597

Study on fatty acid supplement for GI upset during radiation ... In this study, we want to learn more about the effect of investigational Short-chain fatty acids (SCFA) on quality of life and treatment-related side effects ...