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

Trial Summary

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 data supports the effectiveness of the treatment Time-restricted eating plus healthy diet for liver cancer?

Research shows that time-restricted eating can help prevent liver damage and cancer progression in experimental models. It reduces inflammation and supports liver health, which may help in managing liver cancer. ^{1 2 3 4 5}

Is time-restricted eating safe for humans?

Research on time-restricted eating in animals suggests it may have protective effects against cancer and improve liver health, but it can also increase collagen deposits and enhance certain cancer risks in specific conditions. While these studies provide insights, more research is needed to confirm safety in humans. ^{1 2 3 4 6}

How does time-restricted eating plus a healthy diet differ from other treatments for liver cancer?

Time-restricted eating combined with a healthy diet is unique because it focuses on limiting the hours during which food is consumed, which may help prevent liver cancer by reducing inflammation and supporting the liver's natural rhythms. This approach is different from traditional treatments that often involve medication or surgery, as it uses dietary timing and nutrition to potentially slow cancer progression. ^{2 7 8 9 10}

What is the purpose of this trial?

This is a feasibility study that will collect data to assess the potential effect of a nutritional intervention designed to improve liver metabolism. This prospective single-site trial will enroll adult patients undergoing liver-directed therapies for hepatocellular carcinoma. Eligible individuals who are randomized to the intervention group will be enrolled in a six-month nutritional change program consisting of time-restricted eating in which calorie consumption is limited to 8-10 hours during the day, plus targeted healthy changes in what they eat. The intervention includes dietary counseling visits with a study registered dietitian and motivational phone calls with a study Certified Health and Wellness Coach to help subjects adhere to the intervention. Individuals in the control group will be enrolled in a six-month period of observation only. The main questions it aims to answer are: Is a prolonged nightly fast coupled with a healthy diet safe and feasible for patients with liver cancer? Does the intervention improve liver metabolism?

Research Team

Nick Webster, PhD

Principal Investigator

Universoty of California San Diego

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Time-caloric restriction inhibits the neoplastic transformation of cirrhotic liver in rats treated with diethylnitrosamine. [2018]

3. Greece 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. [2020]

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

Effects of short-term dietary restriction on survival of mammary ascites tumor-bearing rats. [2019]

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

Protective effects of short-term dietary restriction in surgical stress and chemotherapy. [2018]

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

Effect of fasting/refeeding on the incidence of chemically induced hepatocellular carcinoma in the rat. [2019]

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

Effect of time restricted feeding on the gut microbiome in adults with obesity: A pilot study. [2022]

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

Effects of time-restricted feeding (16/8) combined with a low-sugar diet on the management of non-alcoholic fatty liver disease: A randomized controlled trial. [2023]

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

Effects of Time-Restricted Eating on Nonalcoholic Fatty Liver Disease: The TREATY-FLD Randomized Clinical Trial. [2023]

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

Changes in body weight and metabolic risk during time restricted feeding in premenopausal versus postmenopausal women. [2023]