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

Trial Summary

What is the purpose of this trial?

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 identifying a safe, low-cost therapeutic to reduce GI toxicity from therapeutic or environmental radiation.

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.

What data supports the effectiveness of SCFA Supplementation for treating radiation poisoning?

Research shows that short-chain fatty acids (SCFAs) have been used effectively to treat various bowel conditions, and SCFA enemas have been explored for treating radiation proctitis, a condition related to radiation exposure. This suggests potential benefits of SCFA supplementation in managing radiation-related intestinal issues. ^{1 2 3 4 5}

Is SCFA supplementation safe for humans?

Short-chain fatty acids (SCFA) have been used safely in treatments for conditions like radiation proctitis and colitis, providing energy for colon cells and supporting gut health. However, most safety data come from animal studies, and more well-controlled human studies are needed to fully understand their safety. ^{1 6 7 8 9}

How does SCFA supplementation differ from other treatments for radiation poisoning?

SCFA supplementation is unique because it uses short-chain fatty acids, which are the main energy source for colon cells, to help repair and protect the gut lining. Unlike other treatments, SCFAs can be administered orally or as enemas, and they have shown effectiveness in reducing inflammation and damage in conditions like radiation proctitis, where no standard treatment exists. ^{1 5 6 8 10}

Research Team

Shivani Sud, MD

Principal Investigator

UNC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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 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]

References

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

Evaluation of short-chain fatty acid enemas: treatment of radiation proctitis. [2004]

2. Switzerland 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. [2021]

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

Saturated fatty acid diet prevents radiation-associated decline in intestinal uptake. [2017]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Parenteral feeding during radiotherapy of oncological patients]. [2015]

5. United States 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. [2019]

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

Short chain fatty acids are effective in short-term treatment of chronic radiation proctitis: randomized, double-blind, controlled trial. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Butyrate enema therapy stimulates mucosal repair in experimental colitis in the rat. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Short chain fatty acids in human gut and metabolic health. [2021]

10. United States 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. [2013]