NEAAR Medical Food for Rectal Cancer

(NEAAR-LARC Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Richard R Tuli, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of South Florida

Must not be taking: Protein supplements

Disqualifiers: Insulin-dependent diabetes, Cachexia, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This clinical study aims to assess feasibility, safety, tolerability, and compliance of a Nonessential Amino Acid Restriction (NEAAR) medical food in adult patients with locally advanced rectal cancer during standard of care short course radiotherapy followed by standard of care chemotherapy.

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 take any protein or amino acid supplements.

What data supports the effectiveness of the NEAAR Medical Food treatment for rectal cancer?

Research shows that certain nutritional approaches, like those involving amino acids and other nutrients, can help improve recovery and reduce complications in cancer patients. For example, a study found that glutamine, an amino acid, reduced postoperative complications and improved recovery in rectal cancer patients. This suggests that similar nutritional strategies, like NEAAR Medical Food, might also be beneficial. ^{1 2 3 4 5}

Is NEAAR Medical Food safe for humans?

Medical foods, like NEAAR Medical Food, are designed to be safe and are made with ingredients that are generally recognized as safe (GRAS). They are used under a doctor's guidance for managing specific health conditions. ^{6 7 8 9 10}

How does the NEAAR Medical Food treatment for rectal cancer differ from other treatments?

The NEAAR Medical Food treatment for rectal cancer is unique because it focuses on nutritional intervention, potentially using specific food components to support health during cancer treatment. Unlike traditional treatments like chemotherapy or radiation, this approach may involve dietary changes or supplements to improve nutritional status and overall well-being, although its direct impact on cancer progression is not well-established. ^{11 12 13 14 15}

Research Team

Richard R Tuli, MD

Principal Investigator

University of South Florida

Eligibility Criteria

This trial is for adults with locally advanced rectal cancer. Participants should be able to follow a special diet (NEAAR Medical Food) during standard radiotherapy and chemotherapy treatments.

Inclusion Criteria

My cancer has not spread to distant parts of my body.

My diagnosis is rectal adenocarcinoma.

My cancer is at stage II or III according to MRI results.

Exclusion Criteria

Receiving other anticancer or experimental therapy

I use insulin for my diabetes.

Patients unable to undergo MRI

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive standard of care short course radiotherapy

1-2 weeks

Chemotherapy

Participants receive standard of care chemotherapy in combination with NEAAR medical food

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• NEAAR Medical Food (Other)

Trial Overview The study tests the NEAAR Medical Food's effects on patients undergoing typical treatment for rectal cancer, including its feasibility, safety, how well people can stick to it, and if it causes any discomfort.

Participant Groups

Group I: Nonessential Amino Acid Restriction (NEAAR) Medical Food Experimental Treatment 1 Intervention

This is a single arm study in which all subjects will receive NEAAR medical food.

Who Is Running the Clinical Trial?

University of South Florida

Lead Sponsor

Trials

433

Recruited

198,000+

Dr. Barbara White

University of South Florida

Chief Medical Officer since 2021

MD, University of Pennsylvania School of Medicine

Dr. Sylvia W. Thomas

University of South Florida

Chief Executive Officer since 2023

Ph.D. in Electrical Engineering, University of South Florida

Findings from Research

In a study of 154 patients recovering from upper gastrointestinal surgery, early enteral feeding with an immunonutritional diet (supplemented with arginine, dietary nucleotides, and omega-3 fatty acids) significantly reduced late postoperative complications compared to a standard control diet, with fewer patients experiencing issues after the fifth postoperative day (5 vs. 13).

The immunonutrition group also demonstrated a substantial cost reduction in treating complications, amounting to approximately 38,867 German marks less than the control group, highlighting both clinical and economic benefits of this dietary intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients. Senkal, M., Mumme, A., Eickhoff, U., et al.[2019]

In a longitudinal study of colorectal cancer patients, symbiotic supplementation led to a significant reduction in C-reactive protein (CRP) levels from 11 mg/dL to below 6 mg/dL, indicating decreased systemic inflammation.

While albumin and carcino-embryonic antigen (CEA) levels remained stable, the reduction in CRP suggests that symbiotic supplementation may help improve the nutritional status and inflammatory response in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional status and systemic inflammatory activity of colorectal patients on symbiotic supplementation. de Oliveira, AL., Aarestrup, FM.[2019]

In a pilot study involving 22 colorectal cancer patients, the amino-acid-rich elemental diet Elental(®) significantly reduced the severity of chemotherapy-induced oral mucositis, with 18 out of 22 patients showing improvement during the first treatment course (p = 0.0002) and 20 out of 22 during the second course (p < 0.0001).

Factors such as the intake of Elental(®), prior use of the diet, and dose reductions of chemotherapy drugs were identified as significant contributors to its effectiveness in preventing oral mucositis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventive effects of amino-acid-rich elemental diet Elental® on chemotherapy-induced oral mucositis in patients with colorectal cancer: a prospective pilot study. Ogata, Y., Ishibashi, N., Yamaguchi, K., et al.[2022]

Enteral nutrition (EN) through oral nutritional supplements (ONS) and tube feeding (TF) is crucial for cancer patients experiencing undernutrition or significantly reduced food intake, especially if this condition lasts more than 7-10 days.

Standard formulas are recommended for EN, and it is particularly beneficial preoperatively for major abdominal surgeries and during radiotherapy to prevent weight loss, while routine EN is not advised during high-dose chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology. Arends, J., Bodoky, G., Bozzetti, F., et al.[2022]

In a study of 208 rectal cancer patients who received neoadjuvant therapy and underwent surgery, intravenous glutamine supplementation significantly reduced postoperative complications and shortened recovery times compared to those who did not receive glutamine.

Patients receiving glutamine had improved outcomes, including a shorter length of hospital stay and quicker return to normal functions like defecation and diet intake, along with better maintenance of albumin levels, indicating enhanced recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Glutamine on Short-term Surgical Outcomes in Rectal Cancer Patients Receiving Neoadjuvant Therapy: A Propensity Score Matching Study. Tang, G., Pi, F., Wei, Z., et al.[2023]

Medical foods are a unique category of therapeutic agents established under the Orphan Drug Act of 1988, specifically designed for the nutritional management of certain diseases and used under physician guidance.

These products, which include formulations for conditions like hyperhomocysteinemia and pancreatic exocrine insufficiency, contain ingredients that are generally recognized as safe (GRAS), ensuring their safety for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical foods: products for the management of chronic diseases. Morgan, SL., Baggott, JE.[2019]

Medical foods, regulated by the FDA, are specifically designed to manage chronic conditions and diseases by meeting unique nutritional needs, and they have proven efficacy in treating various gastrointestinal disorders.

Examples of medical foods include EnteraGam for diarrhea-predominant irritable bowel syndrome, VSL#3 for pouchitis, and Modulen IBD for Crohn's disease, highlighting their safety and effectiveness as complementary therapies alongside traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Emerging Therapeutic Role of Medical Foods for Gastrointestinal Disorders. Ciampa, BP., Reyes Ramos, E., Borum, M., et al.[2020]

Restrictive neutropenic diets, which eliminate many foods to prevent infections in cancer patients, do not show any superior effectiveness in reducing infection rates compared to more liberalized diets.

Adhering to Safe Food-Handling guidelines is sufficient to protect against food-borne infections, suggesting that the neutropenic diet is unnecessary and may compromise the nutritional intake of vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Things We Do For No Reason: Neutropenic Diet. Wolfe, HR., Sadeghi, N., Agrawal, D., et al.[2019]

The study established no observed adverse effect levels (NOAELs) for supplemental methionine (46 mg/kg/d), histidine (8.0 g/d), and lysine (6.0 g/d) in healthy adults, indicating these amounts are safe for consumption in fortified foods or dietary supplements.

These safety recommendations are crucial for regulatory and nutritional practices, as they guide the safe use of amino acids in various dietary contexts aimed at improving health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proposals for Upper Limits of Safe Intake for Methionine, Histidine, and Lysine in Healthy Humans. Cynober, L., Bier, DM., Stover, P., et al.[2023]

Nonessential amino acids (NEAAs) are important in our diet, and their intake should be about two to three times that of essential amino acids (EAAs) to maintain proper nitrogen balance, especially under certain conditions like pregnancy or unbalanced diets.

A new method to estimate NEAA requirements in humans is suggested, highlighting the need for further research to better understand how much NEAA we actually need for optimal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are there dietary requirements for dispensable amino acids and if so, how do we assess requirements? Tessari, P.[2020]

There is no confirmed link between fat consumption and breast or colon cancer, but alcohol consumption is associated with an increased risk of cancers in the oral cavity, pharynx, larynx, and esophagus.

A balanced diet rich in fruits and vegetables is recommended for cancer patients, as it does not differ significantly from the diet of healthy individuals, and early nutritional intervention is crucial to prevent clinical depletion during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nutrition and cancer: causative, protective and therapeutic aspects]. van den Brandt, PA., Dagnelie, PC., von Meyenfeldt, MF.[2018]

A pilot clinical trial with 29 overweight/obese volunteers showed that consuming heat-stabilized rice bran (30 g/day) or cooked navy bean powder (35 g/day) for 28 days increased gut bacterial diversity and altered gut microbial composition, which may influence intestinal health.

While both dietary interventions increased total fiber intake, only rice bran significantly decreased the Firmicutes:Bacteroidetes ratio and increased short-chain fatty acids (SCFAs) like propionate and acetate in stool after 14 days, highlighting that not all fiber sources have the same effects on gut microbiota.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary supplementation with rice bran or navy bean alters gut bacterial metabolism in colorectal cancer survivors. Sheflin, AM., Borresen, EC., Kirkwood, JS., et al.[2022]

In a study of 348 colon cancer patients and 194 rectal cancer patients compared to 542 neighborhood controls, saturated fat was identified as a major risk factor for colon cancer, with no significant protective effect from dietary fiber or cruciferous vegetables.

For rectal cancer, while saturated fat was a risk factor for females in the highest consumption category, specific meats like eggs and beef increased risk for males, and beer consumption was linked to increased risk in females, highlighting the different dietary influences on colon versus rectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food items and food groups as risk factors in a case-control study of diet and colo-rectal cancer. Miller, AB., Howe, GR., Jain, M., et al.[2019]

A diet high in fruits and vegetables, particularly raw ones, is associated with a probable reduction in colorectal cancer risk, while high consumption of refined white flour products and sweets may increase risk, although evidence is still insufficient.

Obesity, especially visceral obesity, is convincingly linked to an increased risk of colorectal cancer, highlighting the importance of maintaining a healthy weight through a balanced diet rich in whole grains, legumes, and low-fat dairy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nutrition and colorectal cancer]. Ströhle, A., Maike, W., Hahn, A.[2017]

In a study of 81 colorectal cancer patients in Pakistan, nearly half reported significant weight loss in the past 3-6 months, indicating compromised nutritional health.

Patients with a higher Prognostic Nutrition Index (PNI) had better nutritional status, including higher body weight and energy intake, while those with lower PNI showed signs of poorer immunological health, such as higher inflammation markers and lower antioxidant defense.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional, immunological and antioxidant defense status of outpatients diagnosed with colorectal cancer - a case-control study of the little-studied population. Alam, I., Alam, W., Aljuraiban, GS., et al.[2021]

References

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

Early postoperative enteral immunonutrition: clinical outcome and cost-comparison analysis in surgical patients. [2019]

2. Brazil pubmed.ncbi.nlm.nih.gov

Nutritional status and systemic inflammatory activity of colorectal patients on symbiotic supplementation. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Preventive effects of amino-acid-rich elemental diet Elental® on chemotherapy-induced oral mucositis in patients with colorectal cancer: a prospective pilot study. [2022]

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

ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology. [2022]

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

Effect of Glutamine on Short-term Surgical Outcomes in Rectal Cancer Patients Receiving Neoadjuvant Therapy: A Propensity Score Matching Study. [2023]

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

Medical foods: products for the management of chronic diseases. [2019]

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

The Emerging Therapeutic Role of Medical Foods for Gastrointestinal Disorders. [2020]

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

Things We Do For No Reason: Neutropenic Diet. [2019]

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

Proposals for Upper Limits of Safe Intake for Methionine, Histidine, and Lysine in Healthy Humans. [2023]

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

Are there dietary requirements for dispensable amino acids and if so, how do we assess requirements? [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

[Nutrition and cancer: causative, protective and therapeutic aspects]. [2018]

12. Germany pubmed.ncbi.nlm.nih.gov

Dietary supplementation with rice bran or navy bean alters gut bacterial metabolism in colorectal cancer survivors. [2022]

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

Food items and food groups as risk factors in a case-control study of diet and colo-rectal cancer. [2019]

14. Germany pubmed.ncbi.nlm.nih.gov

[Nutrition and colorectal cancer]. [2017]

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

Nutritional, immunological and antioxidant defense status of outpatients diagnosed with colorectal cancer - a case-control study of the little-studied population. [2021]