Time-Restricted Eating for Liver Cancer

(TRE+HE Trial)

Overseen By Tanya Shekhtman

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must not be taking: Metabolic biomarkers

Disqualifiers: Advanced HCC, Cirrhosis, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 6 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether time-restricted eating can safely and effectively improve liver health in patients with liver cancer. Participants in the experimental group will limit their food intake to 8-10 hours each day and make healthy diet changes, supported by a dietitian and health coach. The study aims to determine if this approach is feasible and beneficial for liver metabolism. Ideal candidates are adults referred for liver-specific treatments who typically fast for less than 12 hours at night and are willing to follow study guidelines. As an unphased trial, this study offers patients the opportunity to contribute to innovative research that could enhance liver health management.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but it excludes those on medications that significantly affect metabolic study markers. It's best to discuss your specific medications with the trial team.

What prior data suggests that this nutritional intervention is safe for patients with liver cancer?

Research has shown that time-restricted eating, when combined with a healthy diet, is generally safe and easy to follow. New evidence suggests that intermittent fasting might lower cancer risk and enhance the body's response to cancer treatments.

Early results indicate that time-restricted eating is not only feasible but also acceptable for people with cancer, potentially improving their quality of life and demonstrating good tolerance. One study found that this method helps reduce liver fat and improve body weight and metabolism without major side effects.

These findings suggest that time-restricted eating is a safe option for those with liver issues, including individuals receiving treatment for liver cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about time-restricted eating as a treatment for liver cancer because it offers a non-invasive approach that could complement existing therapies like surgery, chemotherapy, and targeted drug treatments. Unlike traditional treatments that often involve medication or procedures, time-restricted eating focuses on when you eat rather than what you eat. This method may help improve metabolic health and potentially slow cancer progression by aligning eating patterns with the body’s natural circadian rhythms. This approach is unique because it empowers patients to make lifestyle changes that might enhance their overall treatment outcomes without the side effects associated with conventional therapies.

What evidence suggests that time-restricted eating plus a healthy diet might be an effective treatment for liver cancer?

This trial will compare time-restricted eating plus a healthy diet with a control observational arm. Studies have shown that time-restricted eating, where eating occurs only during an 8-hour period each day, can improve liver function and may reduce the risk of liver cancer. Emerging evidence suggests that intermittent fasting might lower cancer risk and enhance treatment effectiveness and tolerability. Research also indicates that time-restricted eating is manageable for people with cancer and can enhance their quality of life. Additionally, fasting has improved the effectiveness of liver cancer treatments by supporting beneficial metabolic changes. ^{1 3 6 7 8}

Who Is on the Research Team?

Nick Webster, PhD

Principal Investigator

Universoty of California San Diego

Are You a Good Fit for This Trial?

This trial is for adults with liver cancer, specifically hepatocellular carcinoma, who may also be overweight or have fatty liver disease. Participants should be undergoing liver-directed therapies and willing to follow a nutritional program including time-restricted eating and diet changes.

Inclusion Criteria

Usual nightly fasting <12 hours

Willing to comply with all study procedures

My liver functions well despite my condition.

Exclusion Criteria

Participation in another conflicting study that requires modification of diet or food timing

Active alcohol abuse or less than 6 months of sobriety

Participation in a trial of an investigational agent within the prior 30 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants in the intervention group follow a six-month nutritional change program with time-restricted eating and dietary counseling, while the control group undergoes observation.

6 months

Regular dietary counseling visits and motivational phone calls

Follow-up

Participants are monitored for safety, adherence, and various health outcomes such as insulin levels, glucose levels, and quality of life.

6 months

Assessments at baseline, 3 months, and 6 months

Long-term follow-up

Assessment of disease progression and tumor regression or recurrence using LI-RADS-TR.

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Time-restricted eating plus healthy diet

Trial Overview The study tests if limiting eating to an 8-10 hour window daily combined with a healthy diet can improve liver metabolism in liver cancer patients. It includes dietary counseling and motivational support versus a control group under observation only.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Intervention group will follow time-restricted consumption of a healthy diet.

Group II: Control Active Control 1 Intervention

Control observational arm.

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Published Research Related to This Trial

Short-term dietary restriction, involving alternate day feeding and fasting, significantly improved survival rates in tumor-bearing Fisher rats, with 66.7% surviving 9 days post-tumor inoculation compared to only 20.8% in the control group.

The study suggests that mild dietary restrictions could be beneficial in enhancing survival and potentially inhibiting cancer growth, indicating a need for further clinical trials in human cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of short-term dietary restriction on survival of mammary ascites tumor-bearing rats. Siegel, I., Liu, TL., Nepomuceno, N., et al.[2019]

In an 8-week study of time-restricted feeding (TRF) involving 32 women (13 premenopausal and 19 postmenopausal), both groups experienced similar weight loss of about 3.3% without any significant differences between them.

Both premenopausal and postmenopausal women showed reductions in fat mass, lean mass, fasting insulin, and oxidative stress markers, indicating that TRF can provide metabolic benefits regardless of menopausal status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in body weight and metabolic risk during time restricted feeding in premenopausal versus postmenopausal women. Cienfuegos, S., Gabel, K., Kalam, F., et al.[2023]

Time-restricted feeding (TRF) significantly reduced the expression of genes related to lipid metabolism in mammary tumors, suggesting a potential mechanism for its protective effects against tumor development.

Despite TRF not altering the overall metabolic profile of the tumors, its protective effects may be due to changes in the host's biological pathways rather than direct effects on tumor metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolome of Mammary Tumors Differs from Normal Mammary Glands But Is Not Altered by Time-restricted Feeding Under Obesogenic Conditions. Yan, L., Sundaram, S., Rust, BM., et al.[2020]

In a 12-month clinical trial involving 88 participants with obesity and nonalcoholic fatty liver disease (NAFLD), both time-restricted eating (TRE) and daily calorie restriction (DCR) resulted in similar reductions in intrahepatic triglyceride (IHTG) content, indicating that TRE does not offer additional benefits over DCR for this condition.

Both TRE and DCR led to significant reductions in liver stiffness, body weight, and metabolic risk factors, emphasizing that caloric intake restriction is crucial for managing NAFLD, regardless of the eating pattern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Time-Restricted Eating on Nonalcoholic Fatty Liver Disease: The TREATY-FLD Randomized Clinical Trial. Wei, X., Lin, B., Huang, Y., et al.[2023]

Daily caloric restriction (CR) offers more effective protection against tumor growth and lung metastasis in a breast cancer model compared to periodic caloric cycling with a fasting-mimicking diet (FMD).

The enhanced cancer protection from daily CR may be linked to a distinct immune response that is not replicated by the FMD, suggesting that the consistency of dietary restriction plays a crucial role in cancer prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition. Pomatto-Watson, LCD., Bodogai, M., Bosompra, O., et al.[2023]

Reduced caloric intake and dietary composition may enhance longevity and reduce the severity of aging-related diseases like cancer, suggesting that diet plays a crucial role in health outcomes.

The review proposes that preventive dietary recommendations could improve cancer treatment efficacy and surgical outcomes, highlighting the need for clearer nutritional guidance for patients undergoing cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective effects of short-term dietary restriction in surgical stress and chemotherapy. Brandhorst, S., Harputlugil, E., Mitchell, JR., et al.[2018]

In a 12-week study involving 14 adults with obesity, time-restricted feeding (8-hour eating window) led to a significant weight loss of about 2 kg, indicating potential efficacy for weight management.

Despite the weight loss, the study found no significant changes in the diversity or composition of the gut microbiome, suggesting that time-restricted feeding may not impact gut health in terms of microbial diversity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of time restricted feeding on the gut microbiome in adults with obesity: A pilot study. Gabel, K., Marcell, J., Cares, K., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11048121/

Time-Restricted Feeding Attenuates Metabolic Dysfunction ... We found that restricting food intake to an eight-hour window during the active phase improved liver metabolism and reduced liver cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9600146/

Is Fasting Good When One Is at Risk of Liver Cancer? - PMC Emerging evidence suggests that intermittent fasting can reduce the risk of cancer development and could improve response and tolerance to treatment.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1550413124001359

A 5:2 intermittent fasting regimen ameliorates NASH and ... We identified that an IF 5:2 regimen prevents NASH development as well as ameliorates established NASH and fibrosis without affecting total calorie intake.

4. academic.oup.com academic.oup.com/nutritionreviews/article/83/7/e1660/7745808

Clinical Impact of Time-restricted Eating on Cancer Preliminary findings suggest that TRE is feasible and acceptable by people with cancer, may have oncological benefits, and improves quality of life.

5. science.org science.org/doi/10.1126/sciadv.abh2635

Fasting improves therapeutic response in hepatocellular ... Fasting improves therapeutic response in hepatocellular carcinoma through p53-dependent metabolic synergism | Science Advances.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06824974

To Test Whether Time-restricted Eating Coupled With a ... This is a feasibility study that will collect data to assess the potential effect of a nutritional intervention designed to improve liver metabolism.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S016882782502272X

Efficacy and safety of time-restricted eating in metabolic ... TRE effectively reduces hepatic steatosis in MASLD, with comparable benefits on weight loss, body composition, and metabolic parameters as CR.

8. cih.ucsd.edu cih.ucsd.edu/research/time-restricted-and-healthy-eating-hepatocellular-carcinoma

Time-Restricted and Healthy Eating in Hepatocellular ... A feasibility and safety study of a time-restricted, healthy eating intervention in patients undergoing liver-directed therapies for Hepatocellular carcinoma ( ...