Feasibility Study of Time Restricted Eating and a Healthy Diet in Patients Receiving Liver-Directed Therapy for Hepatocellular Carcinoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Adherence to protocol
研究概览
简要总结
This is a feasibility study that will collect data to assess the potential effect of nutritional intervention. This prospective single-site trial will enroll adult patients with liver diseases such as metabolic-dysfunction associated steatotic liver disease (MASLD), metabolic-dysfunction associated steatohepatitis (MASH), cirrhosis and/or hepatocellular carcinoma (HCC). Eligible individuals who are randomized to the intervention group will be enrolled in a six-month nutritional change program consisting of time-restricted eating plus targeted healthy changes in what they eat (TR-HE). The intervention includes dietary counseling visits with a study registered dietitian (RD) and motivational phone calls with a study Certified Health and Wellness Coach (HC). Individuals who are randomized to the control group or who elect to join the control group will be enrolled in a six-month period of observation and phlebotomy 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 disease or cancer? Does the intervention improve liver metabolism?
详细描述
We are proposing a feasibility study that will collect data to assess the potential effect of nutritional intervention in adult patients with liver disease. We hypothesize that a time-restricted, healthy eating intervention is feasible and safe;will improve metabolic and inflammatory biomarkers, and quality of life.
Primary endpoint is to assess feasibility and safety. Feasibility assessment includes recruitment, retention, and satisfaction of subject; data collection efficiency; adherence to TR+HE protocols by dietary logs and/or dietary recalls. Safety assessment includes liver function tests, hypoglycemic episodes, nausea, disrupted sleep, decreased quality of life or other patient reported events from surveys. Secondary endpoint is to assess clinical parameters including quality of Life (SF-36 questionnaire), sleep disturbance (PROMIS-8b), anthropometrics and vitals, food frequency questionnaire, adiposity by dual-energy X-ray absorptiometry (DEXA), physical activity by accelerometer, glucose levels by continuous glucose monitoring, plasma metabolic markers by fasting glucose, insulin, beta-hydroxy-butyrate, Hemoglobin A1C, leptin, and inflammatory cytokines.
This prospective, single-site, open-label controlled clinical trial will enroll up to 70 overweight or obese adults (BMI at least 27, aged 18 years or more) diagnosed with metabolic liver disease up to and including HCC (BCLC early to intermediate stage), and whose usual nightly fasting interval is less than 12 hours.
The trial will have two arms: the Time Restricted + Healthy Eating (TR+HE) group (14-16 h fast with no energy intake after 7 pm), and the Control (CTL) Group. We will randomize the subjects 2:1 to the intervention group versus the control group. Once the intervention group is full, we will direct any new subjects to the control group. The control group is monitoring plus blood draws. If we have difficulty filling the control group we can use historical SOC data. Participants will be assigned to the TR+HE or the CTL group based on the baseline assessment of the usual nightly fasting and subjects willingness to adhere to the intervention.
All subjects will receive standard of care (SOC) treatment, with additional study-related visits for DXA, accelerometry and CGM instructions, blood draws for metabolic and inflammatory panels, and other clinical assessments. Participants will be provided with mail-in stool samplers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Overweight or obese (BMI 27-45 kg/m2)
- •Diagnosed with metabolic-dysfunction associated steatitic liver disease (MASLD/NAFLD), metabolic-dysfunction associated steatohepatitis, cirrhosis or liver cancer (BCLC early to intermediate stage HCC)
- •English or Spanish speaking over the age of
- •ECOG Performance Status ≤
- •Usual nightly fasting <12 hours
- •Willing to comply with all study procedures
- •Life expectancy of > 12 months
排除标准
- •Advanced HCC, progression, and/or associated comorbidities
- •Metastatic disease, tumor in vein, or ascites
- •Advanced Cirrhosis (hypoalbuminemia/Child-Pugh B+C).
- •Poorly controlled or refractory (grade 3-4) hepatic encephalopathy
- •Type 1 diabetes or self-reported hypoglycemia or hypoglycemic events by CGM
- •Participation in another conflicting study that requires modification of diet or food timing.
- •Patients on GLP-1 receptor agonists
- •Uncontrollable eating pattern (e.g., wasting, Night Eating Syndrome, disordered eating habits, food insecurity)
- •Medications that markedly impact metabolic study biomarkers.
- •Other cancer in last 10 years (other than nonmelanoma skin cancer or carcinoma of the cervix in situ)
- •Serious medical conditions such as chronic kidney disease, congestive heart failure, or any condition that would interfere with participation in the trial.
- •Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy
- •Active alcohol abuse or less than 6 months of sobriety
- •Participation in a trial of an investigational agent within the prior 30 days
- •Pregnancy or lactating, positive hCG urine test.
研究组 & 干预措施
Intervention
Intervention group will follow time-restricted consumption of a healthy diet.
干预措施: Time-restricted eating plus healthy diet (Behavioral)
Control
Control observational arm.
结局指标
主要结局
Adherence to protocol
时间窗: 6 months
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.
Safety from adverse events
时间窗: 6 months
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.
Ability to recruit
时间窗: 6 months
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.
Satisfaction and self-motivation
时间窗: 6 months
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.
次要结局
- Effect of intervention on ketone production(6 months)
- Effect of interventions on hemoglobin A1c(6 months)
- Effect of intervention on plasma leptin(6 months)
- Effect of intervention on inflammatory cytokines(6 months)
- Effect of intervention on fecal microbiome(6 months)
- Effect of intervention on Quality of Life(6 months)
- Effect of interventions on fasting glucose(6-months)
- Sleep disturbance(6 months)
- Effect of intervention on body weight(6 months)
- Effect of intervention on food frequency(6 months)
- Effect of intervention on Adiposity(6 months)
- Effect of interventions on Physical activity(6 months)
- Effect of intervention on Glucose levels(6 months)
- Effect of intervention on fasting insulin(6 months)
研究者
Nicholas Webster
Professor of Medicine
University of California, San Diego