To Test Whether Time-restricted Eating Coupled With a Healthy Diet is Beneficial in Liver Cancer Patients (TRE+HE)

Feasibility Study of Time Restricted Eating and a Healthy Diet in Patients Receiving Liver-Directed Therapy for Hepatocellular Carcinoma

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?

Study Overview

• Status: Recruiting
• Conditions: Liver Cancer, Adult; Obesity and Overweight; MASH - Metabolic Dysfunction-Associated Steatohepatitis
• Intervention / Treatment: Behavioral: Time-restricted eating plus healthy diet

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nick Webster, PhD; Phone Number: 858-534-6275; Email: nwebster@health.ucsd.edu
• Study Contact Backup: Name: Tanya Shekhtman; Email: tshekhtman@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California San Diego
      • Contact: Nick Webster; Phone Number: 8585346275; Email: nwebster@health.ucsd.edu
      • Principal Investigator: Nick Webster, Ph.D., M.A.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Overweight or obese (BMI 27-45 kg/m2)
2. BCLC early to intermediate stage HCC
3. Referred for liver-directed therapy (PTA, TACE, TARE within 3 months)
4. English or Spanish speaking over the age of 18.
5. ECOG Performance Status ≤ 2.
6. Usual nightly fasting <12 hours
7. Willing to comply with all study procedures
8. Child-Pugh A liver function.

Exclusion Criteria:

1. Advanced HCC, progression, and/or associated comorbidities, metastatic disease, tumor in vein, or ascites
2. Advanced Cirrhosis (hypoalbuminemia/Child-Pugh B+C). Poorly controlled or refractory (grade 3-4) hepatic encephalopathy
3. Type 1 diabetes or self-reported hypoglycemia or hypoglycemic events by CGM
4. Participation in another conflicting study that requires modification of diet or food timing.
5. Uncontrollable eating pattern (e.g., wasting, Night Eating Syndrome, disordered eating habits, food insecurity)
6. Medications that markedly impact metabolic study biomarkers.
7. Other cancer in last 10 years (other than nonmelanoma skin cancer or carcinoma of the cervix in situ)
8. Serious medical conditions such as chronic kidney disease, congestive heart failure, or any condition that would interfere with participation in the trial.
9. Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy
10. Active alcohol abuse or less than 6 months of sobriety
11. Participation in a trial of an investigational agent within the prior 30 days
12. Pregnancy or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Intervention group will follow time-restricted consumption of a healthy diet.	Behavioral: Time-restricted eating plus healthy diet; Subjects will restrict calorie consumption to 8-10 hours during the day plus will follow a healthy plant-based diet.
No Intervention: Control; Control observational arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to protocol	Participant adherence to and comprehension of the protocol as an indicator of intervention delivery by staff. Adherence will be assessed by the number of participants who complete the study, the percentage of days with fasting >14 h, and the number of days that food was logged into the app.	6 months
Safety from adverse events	Safety assessed by adverse events and liver function tests. Reports on adverse events will include hypoglycemic epidoes, nausea, disrupted sleep, decreased quality of life or other patient reported events from surveys. Liver function tests (AST and ALT) as well ss platelet count and total protein are monitored under SOC. AST and ALT elevation will be considered mild if 2-5 times upper limit normal (ULN), moderate if 5-15 times ULN, and severe if >15 times ULN.	6 months
Ability to recruit	Ability to recruit our target population will be assessed by the number of eligible individuals in the patient population, and the number who enroll in the trial.	6 months
Satisfaction and self-motivation	We will determine the degree to which participants liked the intervention through satisfaction surveys at the end of the study and the number of participants who demonstrate self-motivation to continue the intervention protocol during 6-month follow-up.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of intervention on Quality of Life	Quality of Life will be assessed using the EORTC QLQ C-30 questionnaire for Cancer patients	6 months
Effect of interventions on fasting glucose	Fasting glucose will be measured at baseline and 6 months	6-months
Sleep disturbance	Sleep disturbance as reported by the PROMIS-8b survey	6 months
Effect of intervention on body weight	Body weight will be measured prior to and during intervention	6 months
Effect of intervention on food frequency	Participants will complete a Food frequency questionnaire at Baseline, 3 months and 6 months	6 months
Effect of intervention on Adiposity	Adiposity will be measured by Dual-energy X-ray Absorptiometry (DXA) at baseline and at 6 months	6 months
Effect of interventions on Physical activity	Physical activity will be measured by Accelerometer mounted at the waist at baseline and at 6 months	6 months
Effect of intervention on Glucose levels	Glucose levels will be monitored by Continuous Glucose Monitoring at baseline and at 6 months	6 months
Effect of intervention on fasting insulin	Fasting insulin levels will be measured at baseline and at 6 months	6 months
Effect of intervention on ketone production	Fasting beta-hydroxybutyrate levels will be measured at baseline and 6 months	6 months
Effect of interventions on hemoglobin A1c	Hemoglobin A1c will be measured at baseline and 6 months	6 months
Effect of intervention on plasma leptin	Leptin levels will be measured at baseline and 6 months	6 months
Effect of intervention on inflammatory cytokines	Inflammatory cytokines will be measured at baseline and 6 months	6 months
Effect of intervention on fecal microbiome	7S sequencing will be performed on fecal samples at baseline and 6 months	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease progression as a Tertiary/Exploratory outcome	Tumor regression or recurrence will be assessed using LI-RADS-TR.	12-months

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Nick Webster, PhD, Universoty of California San Diego

Publications and helpful links

General Publications

• Das M, Kumar D, Sauceda C, Oberg A, Ellies LG, Zeng L, Jih LJ, Newton IG, Webster NJG. Time-Restricted Feeding Attenuates Metabolic Dysfunction-Associated Steatohepatitis and Hepatocellular Carcinoma in Obese Male Mice. Cancers (Basel). 2024 Apr 16;16(8):1513. doi: 10.3390/cancers16081513.
• Das M, Webster NJG. Obesity, cancer risk, and time-restricted eating. Cancer Metastasis Rev. 2022 Sep;41(3):697-717. doi: 10.1007/s10555-022-10061-3. Epub 2022 Aug 19.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 4, 2025
• First Submitted That Met QC Criteria: February 7, 2025
• First Posted (Actual): February 13, 2025

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: healthy diet; Time-restricted eating
• Additional Relevant MeSH Terms: Nutrition Disorders; Neoplasms by Site; Neoplasms; Overnutrition; Body Weight; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Overweight; Carcinoma, Hepatocellular; Liver Neoplasms; Fatty Liver
• Other Study ID Numbers: #808859

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No