Time-restricted Eating in Patients With Metabolic-associated Steatotic Liver Disease . CHRONOMASLD: A Chrononutrition/Chronotoxicity Randomized Controlled Trial.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 150
- 试验地点
- 2
- 主要终点
- Changes in body weight
研究概览
简要总结
The goal of this clinical trial is to study the effect of a time-restricted eating (TRE) dietary pattern combined with a time of consumption restriction about the daily portions of fruits and vegetables in people diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD).
The protocol of the study is an intention to treat protocol. The main research questions are:
- Does compliance in a TRE dietary scheme (positively) affect changes in body weight and body fat mass in people diagnosed with MASLD?
- Does an additional time restriction on the consumption of fruits and vegetables within the "light-window" of the day affects the metabolism of food contaminants?
Participants will be asked to:
- Adhere to a TRE dietary pattern for 3 months. TRE consists of an 8-hour eating vs 16 hours fasting within the day. First meal of the day should not occur at least an hour after wake-up time and last meal of the day should occur not later than 2 hours before bed-time.
- Adhere to a further time restricted consumption of a "5-a-day" portions of fruits and vegetables between the "light-window hours" between 9am to 4pm.
- Visit the Nutrition & Dietetics Clinic once every month for anthropometric measurements (on 4 time points).
- Collect and deliver first morning urine samples (on 7 time points).
- Collect and deliver saliva samples at baseline and at the end of the trial (Saliva collection should occur every 4-hours for 48-hours including fasting collection at baseline and at the end of three months)
5) Complete a compliance and lifestyle questionnaire questionnaire via telephone interview to the research team every 2 weeks.
6) Share photos to the research team with the use of an application on time of actual fruit and vegetables consumption, 3-4 times per week throughout the study protocol.
Researchers will compare the designed intervention package of this TRE with the Standard of Care (SoC) protocol (based on the international guidelines) that is currently used in daily practice for the management of MASLD.
详细描述
This parallel-arm, randomized controlled trial (RCT) will study the effects of an ad libitum TRE dietary pattern (8 hours eating, 16 hours fasting) with an additional restriction regarding the fruit and vegetable consumption on health parameters, pesticide metabolism and concomitant toxicity in MASLD patients compared with the Standard of Care (SoC) approach, that will serve as the control group. Participants will be asked to consume all meals/snacks during the 8 hours daily period that they will select for themselves without any further dietary advice regarding caloric or other macronutrient intake. However, participants will be instructed that their first meal of the day should not start for at least an hour after wake-up hour and will also be asked to have their last meal at least 2 hours earlier than bedtime (actual time of sleep). Additionally, participants will have to consume 5 portions (400g) of fruits and vegetables within time-window for fruit & vegetable consumption earlier in the day; from 9am to 4pm.
Non-caloric beverage consumption (water, black coffee, unsweetened tea, non-sweetened beverages) will be allowed within the restricted hours of the intervention.
Participants allocated in the SoC group (control) will receive oral and written SoC lifestyle advice from a registered dietitian. The SoC advice is based on the EASL/EASD/EASO joint Clinical Practice Guidelines for the management of MASLD. Patients will receive guidance on a) energy restriction, b) weight reduction, c) the macronutrient composition of the diet, d) limitation of alcohol intake (below the risk threshold of 30g/d and 20g/day for men and women, respectively) and e) increase their physical activity levels. Additionally, in this study patients will be asked to consume standard "5-a-day" portions of fruits and vegetables daily, as part of their dietary healthier behaviour.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body mass index 25 (±0,5)-45(±0,5) kg/m2
- •Clinical diagnosis of MASLD, not excluding undiagnosed NASH or with NASH stage F0-F1
- •Self-reported habitual eating period more than or equal to 14 h per day, BUT NOT LESS.
- •Cyprus inhabitants of for at least 1 year
- •Registered to the National Health System of the Republic of Cyprus (Gesy
排除标准
- •Night Shift worker
- •Fasting >12-h/day more than once a week or > once a week no food intake after 18:00
- •Co-existing causes of chronic liver disease according to standard diagnostic testing including, but not restricted to:
- •Positive hepatitis B surface antigen
- •Positive hepatitis C virus RNA
- •Suspicion of drug-induced liver disease
- •Alcoholic liver disease
- •Autoimmune hepatitis
- •Wilson's disease
- •Hemochromatosis
- •Primary biliary cholangitis or primary sclerosing cholangitis
- •Known or suspected hepatocellular carcinoma
- •Medications which cause liver disease or secondary hepatic steatosis (Tamoxifen, systemic corticosteroids, methotrexate, tetracycline, estrogens, valproic acid, and statin (registration is possible if statin is delivered in a consistent dosage within 12 weeks)
- •Current or recent history (<5 years) of significant alcohol intake (>30g of alcohol/ day or >210g/week for men, >20g of alcohol/day or >140g/week for women)
- •Doctor diagnosed diabetes mellitus on insulin or sulfonylureas
- •Severe medical comorbidities [ischemic heart disease, 3rd degree atrioventricular block, chronic obstructive pulmonary disease, severe hypertension (blood pressure >200/120 mmHg)]
- •Unstable weight (>5% change in the last 2 months) or participation in a weight-loss program within the past 12 weeks
- •Sleep disorder (with a medical diagnosis) or individuals self-reporting sleep difficulties and poor sleep [average sleep less than 6 consecutive hours or patients who systematically experience sleep interruption for more than 2 times each night (waking up for toilet use is not to be considered sleep interruption)]
- •Individuals with food allergies (or hypersensitivity to the fruits and vegetables that will be selected for the study)
- •Systematic organic products consumers (defined as a self-reported usual consumption of more than 80% of their weekly fruits & vegetables being organic)
- •Pregnant or trying to become pregnant or lactating women
- •People not in position to communicate in Greek or English language
- •Having metallic parts in the body.
研究组 & 干预措施
Standard of Care (Group A-Control)
Participants in Group A will follow a Standard of Care Intervention. They will receive guidance on a) energy restriction, b) weight reduction, c) the macronutrient composition of the diet, d) limitation of alcohol intake (below the risk threshold of 30g/d and 20g/day for men and women, respectively) and e) increase their physical activity levels. Additionally, in this study patients will be asked to consume the general recommendation of "5-a-day" as part of their dietary healthier behaviour. Moreover, participants should stay well hydrated and get adequate of sleep (an average of 6 consecutive hours at night). Oral and written guidance for the management of MASLD will be administered. The duration of the intervention is 3 months.
干预措施: Lifestyle Management (Other)
Time-restricted eating (Group B-Intervention)
Participants will have to adhere to an ad libitum TRE dietary pattern (8 hours eating, 16 hours fasting) with an additional dietary restriction regarding the "5-a-day" fruit and vegetable in which they will need to be consumed between 9am-4pm. Some more restrictions regarding first and last meal will be asked. Participants will be instructed that their first meal of the day should not start for at least an hour after wake-up hour and will also be asked to have their last meal at least 2 hours earlier than bedtime (actual time of sleep). The duration of the intervention is 3 months.
干预措施: Diet-Time-restricted eating (TRE) (Other)
结局指标
主要结局
Changes in body weight
时间窗: From enrolment to the end of treatment at 3 months (with two in-between measurement)
Changes in body weight (in kilograms) from baseline to the end of intervention in the TRE and the Soc group (intervention vs control, respectively). Depending on the data distribution, independent samples t-test or Wilcoxon Rank-Sum Test will be used If the changes do or do not follow a normal distribution between baseline and post-treatment are normally distributed, respectively. Mixed Effect Models will be used to assess the main and interaction (included if p\<0.05) effects between groups and time since study initiation adjusting for confounders, including circadian rhythm metrics such as melatonin and/or cortisol.
Changes in body fat mass
时间窗: From enrolment to the end of treatment at 3 months (with one in-between measurement)
Changes in body fat mass (expressed as % of the total body weight in kilograms) from baseline to the end of intervention in the TRE and the Soc group (intervention vs control, respectively). Depending on the data distribution, independent samples t-test or Wilcoxon Rank-Sum Test will be used If the changes do or do not follow a normal distribution between baseline and post-treatment are normally distributed, respectively. Mixed Effect Models will be used to assess the main and interaction (included only if p\<0.05) effects between groups and time since study initiation adjusting for confounders, including circadian rhythm metrics such as melatonin and/or cortisol.
次要结局
- Changes in total cholesterol (TC) levels in blood(From enrolment to the end of treatment at 3 months (one measurement at the beginning and one measurement at the end of the intervention))
- Changes in high-density lipoprotein cholesterol (HDL) levels in blood(From enrolment to the end of treatment at 3 months (one measurement at the beginning and one measurement at the end of the intervention))
- Changes in Pesticide Metabolite 3-phenoxybenzoic Acid (3-PBA) Levels in Urine(From first day of the intervention to the end of treatment at 3 months (with six in between measurements))
- Changes in Pesticide Metabolite 6-chloronicotininc Acid (6-CN) Levels in Urine(From first day of the intervention to the end of treatment at 3 months (with six in between measurements))
- Changes in waist circumference (WC)(From enrolment to the end of treatment at 3 months (with one in-between measurement))
- Changes in 4-Hydroxynonenal (4HNE) Levels in Urine(From first day of the intervention to the end of treatment at 3 months (with six in between measurements))
- Changes in Body Mass Index (BMI)(From enrolment to the end of treatment at 3 months (with two in-between measurement))
- Changes in glucose (Gluc) levels in blood(From enrolment to the end of treatment at 3 months (one measurement at the beginning and one measurement at the end of the intervention))
- Changes in low-density lipoprotein cholesterol (LDL) levels n blood(From enrolment to the end of treatment at 3 months (one measurement at the beginning and one measurement at the end of the intervention))
- Changes in alanine transaminase (ALT) levels n blood(From enrolment to the end of treatment at 3 months (one measurement at the beginning and one measurement at the end of the intervention))
- Changes in aspartate aminotransferase (AST) levels in blood(From enrolment to the end of treatment at 3 months (one measurement at the beginning and one measurement at the end of the intervention))
- Changes in C-Reactive Protein (CRP) levels n blood(From enrolment to the end of treatment at 3 months (one measurement at the beginning and one measurement at the end of the intervention))
研究者
Konstantinos Makris
Professor of Environmental Health
Cyprus University of Technology