Non-alcoholic Fatty Liver Disease (NAFLD) in Overweight and Obese People Under Nutritional and Lifestyle Follow-up: a Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Change from Baseline Weight at 6 months
研究概览
简要总结
Non-alcoholic fatty liver disease (NAFLD) is a condition of excessive hepatic lipid accumulation in subjects that consume less than 20g ethanol per day, without other known causes as drugs consumption or toxins exposure. In Western countries, the rate of this disease lies about 30% in the general adult population. The process of developing NAFLD can start from simple steatosis to non-alcoholic steatohepatitis (NASH), which eventually can lead to cirrhosis and hepatocellular carcinoma in the absence of alcohol abuse. Liver biopsy is considered the "gold standard" of steatosis, fibrosis and cirrhosis. However, it is rarely performed because it is an invasive procedure and investigators are focusing in the application of non-invasive liver damage scores for diagnosis.
The pathogenesis of NAFLD is multifactorial and triggered by environmental factors such as unbalanced diets and overnutrition as well as by lack of physical activity in the context of a genetic predisposition. Nowadays, the treatment of NAFLD is based on diet and lifestyle modifications. Weight loss, exercise and healthy eating habits are the main tools to fight NAFLD. Nevertheless, there is no a well characterized dietary pattern and further studies are necessary.
With this background, the general aim of this project is to increase the knowledge on the influence of nutritional/lifestyle interventions in obese patients with NAFLD, as well as contribute to identify non-invasive biomarkers/scores to early diagnosis of this pathology in future obese people.
详细描述
This project is framed within the promotion of health and lifestyles and, specifically, in liver disorder linked to obesity (FLiO: Fatty Liver in Obesity).
The investigation addresses a randomized, parallel, long-term personalized nutritional intervention with two strategies: 1) Control diet based on American Heart Association (AHA); 2) Fatty Liver in Obesity (FLiO) diet based on previous results (RESMENA project).The diet is based on macronutrient distribution, quality and quantity, and is characterized by a low glycemic load, high adherence to the Mediterranean diet and a high antioxidant capacity, with the inclusion of anti-inflammatory foods. It also takes into account the distribution of food throughout the day, number of meals, portion sizes, timing of meal, individual needs, dietary behavior (behavioral therapy: eat slowly, teach what to buy, what to eat, when to eat). The participants are instructed to follow this strategy. This strategy (RESMENA) was even more effective than AHA after 6 months follow-up, in terms of significant reduction of abdominal fat and blood glucose level. In addition, this diet had beneficial effects for participants who were obese and had values of altered glucose, reducing significantly in RESMENA participants LDL-oxidized marker. These results are very important to apply in the present investigation since that patients with NAFLD are commonly insulin resistant.
Both strategies were designed within a hypocaloric dietary pattern (-30%) in order to achieve the American Association for the Study of Liver Diseases (AASLD) recommendations for the management of non-alcoholic liver disease (loss of at least 3-5% of body weight appears necessary to improve steatosis, but a greater weight loss, up to 10%, may be needed to improve necroinflammation). At this time the participants are individually supervised and encouraged to follow with the dietary planning instructions assigned. Furthermore, at baseline, 6, 12 and 24 months anticipated variables are obtained. Both dietary groups receive routine control (weight, body composition, strategy adherence) and dietary advice daily by phone (if they need help) and face to face at the time of routine control.
In order to get a integral lifestyle intervention, all participants will be encouraged to follow a healthy lifestyle. Thus, physical activity will be recorded in each dietary group.
The specific tasks:
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 (Participant)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Overweight or obese
- •Diagnosis of NAFLD
- •Age: 30-80 years
- •Female / Male
排除标准
- •Known liver disease (other than NAFLD)
- •Abuse of alcohol (>21 and >14 units of alcohol a week for men and women, respectively, eg 1 unit = 125 mL of wine);
- •Drug treatments: immunosuppressants, cytotoxic agents, systemic corticosteroids, agents potentially causing fatty liver disease or abnormal liver tests or weight modifiers
- •Active cancer or a history of malignancy in the last 5 years
- •Problems of massive edemas
- •Obesity known endocrine origin (except treated hypothyroidism)
- •Surgical procedure for weight loss
- •≥ 3kg weight loss in the last 3 months
- •Severe psychiatric disorders
- •Lack of autonomy or inability to follow the diet (including food allergies or intolerances) or/and lifestyle recommendations as well as to follow scheduled visits.
- •Consumption of any type of food supplements (antioxidants, prebiotics, probiotics, etc.)
结局指标
主要结局
Change from Baseline Weight at 6 months
时间窗: Baseline and 6 months
Weight will be measured by a digital scale
Change from Baseline Weight at 12 months
时间窗: Baseline and 12 months
Weight will be measured by a digital scale
Change from 6 month Weight at 12 months
时间窗: 6 months and 12 months
Weight will be measured by a digital scale
次要结局
- Change from Baseline Body fat at 12 months(Baseline and 12 months)
- Change from Baseline Waist circumference at 6 months(Baseline and 6 months)
- Change from 6 month Waist circumference at 12 months(6 months and 12 months)
- Change from Baseline handgrip strength at 12 months(Baseline and 12 months)
- Change from Baseline interleukin 6 (IL-6) concentration at 6 months(Baseline and 6 months)
- Change from Baseline handgrip strength at 6 months(Baseline and 6 months)
- Change from Baseline Systolic blood pressure at 6 months(Baseline and 6 months)
- Change from 6 month Systolic blood pressure at 12 months(6 months and 12 months)
- Change from Baseline Diastolic blood pressure at 6 months(Baseline and 6 months)
- Change from 6 month Diastolic blood pressure at 12 months(6 months and 12 months)
- Change from Baseline Body fat at 6 months(Baseline and 6 months)
- Change from 6 month Body fat at 12 months(6 months and 12 months)
- Change from Baseline Waist circumference at 12 months(Baseline and 12 months)
- Change from Baseline lipid metabolism at 6 months(Baseline and 6 months)
- Change from Baseline Hepatic elastography at 12 months(Baseline and 12 months)
- Change from 6 month handgrip strength at 12 months(6 months and 12 months)
- Change from Baseline Diastolic blood pressure at 12 months(Baseline and 12 months)
- Change from 6 month lipid metabolism at 12 months(6 months and 12 months)
- Change from Baseline uric acid concentration at 12 months(Baseline and 12 months)
- Change from Baseline cytokeratin-18 (CK18) concentration at 12 months(Baseline and 12 months)
- Change from Baseline C-reactive protein (CRP) concentration at 12 months(Baseline and 12 months)
- Change from 6 month leptin concentration at 12 months(6 months and 12 months)
- Change from Baseline LDL-oxidized concentration at 6 months(Baseline and 6 months)
- Change from Baseline LDL-oxidized concentration at 12 months(Baseline and 12 months)
- Change from Baseline Hepatic elastography at 6 months(Baseline and 6 months)
- Change from Baseline insulin concentration at 6 months(Baseline and 6 months)
- Change from Baseline tumor necrosis factor-α (TNFα) concentration at 12 months(Baseline and 12 months)
- Change from Baseline leptin concentration at 6 months(Baseline and 6 months)
- Change from Baseline leptin concentration at 12 months(Baseline and 12 months)
- Change from Baseline adiponectin concentration at 6 months(Baseline and 6 months)
- Change from 6 month plasma antioxidant capacity at 12 months(6 months and 12 months)
- Change from Baseline Systolic blood pressure at 12 months(Baseline and 12 months)
- Change from Baseline lipid metabolism at 12 months(Baseline and 12 months)
- Change from Baseline Hemoglobin A1c concentration at 12 months(Baseline and 12 months)
- Change from Baseline fibroblast growth factor 21 (FGF21) concentration at 6 months(Baseline and 6 months)
- Change from Baseline fibroblast growth factor 21 (FGF21) concentration at 12 months(Baseline and 12 months)
- Change from Baseline cytokeratin-18 (CK18) concentration at 6 months(Baseline and 6 months)
- Change from 6 month C-reactive protein (CRP) concentration at 12 months(6 months and 12 months)
- Change from 6 month adiponectin concentration at 12 months(Baseline and 12 months)
- Change from Baseline adiponectin concentration at 12 months(Baseline and 12 months)
- Change from Baseline uric acid concentration at 6 months(Baseline and 6 months)
- Change from 6 month uric acid concentration at 12 months(6 months and 12 months)
- Change from Baseline Hemoglobin A1c concentration at 6 months(Baseline and 6 months)
- Change from Baseline liver function at 6 months(Baseline and 12 months)
- Change from 6 month cytokeratin-18 (CK18) concentration at 12 months(6 months and 12 months)
- Change from 6 month interleukin 6 (IL-6) concentration at 12 months(6 months and 12 months)
- Change from Baseline tumor necrosis factor-α (TNFα) concentration at 6 months(Baseline and 6 months)
- Change from Baseline Malondialdehyde concentration at 6 months(Baseline and 6 months)
- Change from 6 month homocysteine concentration at 12 months(6 months and 12 months)
- Change from Baseline homocysteine concentration at 6 months(Baseline and 6 months)
- Change from Baseline homocysteine concentration at 12 months(Baseline and 12 months)
- Change from Baseline glucose metabolism at 6 months(Baseline and 6 months)
- Change from 6 month glucose metabolism at 12 months(6 months and 12 months)
- Change from Baseline glucose metabolism at 12 months(Baseline and 12 months)
- Change from 6 month insulin concentration at 12 months(6 months and 12 months)
- Change from Baseline insulin concentration at 12 months(Baseline and 12 months)
- Change from 6 month Hemoglobin A1c concentration at 12 months(6 months and 12 months)
- Change from 6 month liver function at 12 months(6 months and 12 months)
- Change from Baseline liver function at 12 months(Baseline and 12 months)
- Change from 6 month fibroblast growth factor 21 (FGF21) concentration at 12 months(6 months and 12 months)
- Change from Baseline C-reactive protein (CRP) concentration at 6 months(Baseline and 6 months)
- Change from Baseline interleukin 6 (IL-6) concentration at 12 months(Baseline and 12 months)
- Change from 6 month tumor necrosis factor-α (TNFα) concentration at 12 months(6 months and 12 months)
- Change from 6 month LDL-oxidized concentration at 12 months(6 months and 12 months)
- Change from 6 month Malondialdehyde concentration at 12 months(6 months and 12 months)
- Change from Baseline Malondialdehyde concentration at 12 months(Baseline and 12 months)
- Change from Baseline Hepatic echography at 12 months(Baseline and 12 months)
- Change from Baseline Hepatic Magnetic Resonance Imaging at 6 months(Baseline and 6 months)
- Change from 6 month Hepatic echography at 12 months(6 months and 12 months)
- Change from 6 months Physical activity level at 12 months(6 months and 12 months)
- Change from Baseline chair test at 12 months(Baseline and 12 months)
- Change from Baseline sleep quality at 6 months(Baseline and 12 months)
- Change from Baseline Depressive symptoms at 6 months(Baseline and 6 months)
- Change from Baseline Depressive symptoms at 12 months(Baseline and 12 months)
- Change from Baseline plasma antioxidant capacity at 6 months(Baseline and 6 months)
- Change from Baseline plasma antioxidant capacity at 12 months(Baseline and 12 months)
- Change from Baseline Hepatic echography at 6 months(Baseline and 6 months)
- Change from 6 month Hepatic elastography at 12 months(6 months and 12 months)
- Change from 6 month Minnesota Physical Activity test at 12 months(6 months and 12 months)
- Change from Baseline sleep quality at 12 months(Baseline and 12 months)
- Change from Baseline Anxiety symptoms at 6 months(Baseline and 6 months)
- Change from 6 month Anxiety symptoms at 12 months(6 months and 12 months)
- Change from Baseline Gut microbiota composition at 6 months(Baseline and 6 months)
- Change from 6 month metabolites composition of urine at 12 months(6 months and 12 months)
- Change from 6 month Hepatic Magnetic Resonance Imaging at 12 months(6 months and 12 months)
- Change from Baseline Hepatic Magnetic Resonance Imaging at 12 months(Baseline and 12 months)
- Change from Baseline White blood cell count at 6 months(Baseline and 6 months)
- Change from Baseline blood rheological properties at 6 months(Baseline and 6 months)
- Change from Baseline Physical activity level at 6 months(Baseline and 6 months)
- Change from Baseline Minnesota Physical Activity test at 12 months(Baseline and 12 months)
- Change from 6 month number of steps at 12 months(6 months and 12 months)
- Change from Baseline chair test at 6 months(Baseline and 6 months)
- Single Nucleotide polymorphisms (SNPs)(Baseline)
- Change from Baseline satiety index at 6 months(Baseline and 6 months)
- Change from 6 month Ghrelin concentration at 12 months(6 months and 12 months)
- Change from Baseline glucagon-like peptide-1 (GLP-1) concentration at 6 months(Baseline and 6 months)
- Change from 6 month glucagon-like peptide-1 (GLP-1) concentration at 12 months(6 months and 12 months)
- Change from Baseline Dopac concentration at 12 months(Baseline and 12 months)
- Change from Baseline Serotonin (5-HT) concentration at 6 months(Baseline and 6 months)
- Change from 6 month White blood cell count at 12 months(6 months and 12 months)
- Change from Baseline White blood cell count at 12 months(Baseline and 12 months)
- Change from 6 month blood rheological properties at 12 months(6 months and 12 months)
- Change from Baseline blood rheological properties at 12 months(Baseline and 12 months)
- Change from Baseline Physical activity level at 12 months(Baseline and 12 months)
- Change from Baseline Minnesota Physical Activity test at 6 months(Baseline and 6 months)
- Change from Baseline number of steps at 6 months(Baseline and 6 months)
- Change from 6 month chair test at 12 months(6 months and 12 months)
- Change from 6 month sleep quality at 12 months(6 months and 12 months)
- Change from 6 month DNA methylation at 12 months(6 months and 12 months)
- Change from Baseline metabolites composition of serum at 6 months(Baseline and 6 months)
- Change from Baseline number of steps at 12 months(Baseline and 12 months)
- Change from 6 month Depressive symptoms at 12 months(6 months and 12 months)
- Change from Baseline Anxiety symptoms at 12 months(Baseline and 12 months)
- Change from Baseline DNA methylation at 6 months(Baseline and 6 months)
- Change from Baseline DNA methylation at 12 months(Baseline and 12 months)
- Change from Baseline microRNAs at 6 months(Baseline and 6 months)
- Change from 6 month Gut microbiota composition at 12 month(6 months and 12 months)
- Change from 6 month metabolites composition of serum at 12 months(6 months and 12 months)
- Change from Baseline dietary intake at 12 months(Baseline and 12 months)
- Change from Baseline life quality index at 6 months(Baseline and 6 months)
- Change from Baseline glucagon-like peptide-1 (GLP-1) concentration at 12 months(Baseline and 12 months)
- Change from Baseline Dopamine concentration at 6 months(Baseline and 6 months)
- Change from 6 month Dopamine concentration at 12 months(6 months and 12 months)
- Assessment of dietary adherence at 12 months(12 months)
- Change from Baseline 5-hydroxyindoleacetic acetic (5-HIAAC) concentration at 6 months(Baseline and 6 months)
- Change from Baseline Serotonin (5-HT) concentration at 12 months(Baseline and 12 months)
- Change from 6 month microRNAs at 12 months(6 months and 12 months)
- Change from Baseline microRNAs at 12 months(Baseline and 12 months)
- Change from Baseline Gut microbiota composition at 12 month(Baseline and 12 months)
- Change from Baseline metabolites composition of urine at 6 months(Baseline and 6 months)
- Change from Baseline metabolites composition of urine at 12 months(Baseline and 12 months)
- Change from Baseline metabolites composition of serum at 12 months(Baseline and 12 months)
- Change from Baseline dietary intake at 6 months(Baseline and 6 months)
- Change from 6 month dietary intake at 12 months(6 months and 12 months)
- Assessment of dietary adherence at Baseline(Baseline)
- Assessment of dietary adherence at 6 months(6 months)
- Change from 6 month satiety index at 12 months(6 months and 12 months)
- Change from 6 month life quality index at 12 months(6 months and 12 months)
- Change from Baseline satiety index at 12 months(Baseline and 12 months)
- Change from Baseline life quality index at 12 months(Baseline and 12 months)
- Change from Baseline Ghrelin concentration at 6 months(Baseline and 6 months)
- Change from Baseline Ghrelin concentration at 12 months(Baseline and 12 months)
- Change from Baseline Dopamine concentration at 12 months(Baseline and 12 months)
- Change from Baseline Dopac concentration at 6 months(Baseline and 6 months)
- Change from 6 month Dopac concentration at 12 months(6 months and 12 months)
- Change from 6 month Noradrenaline concentration at 12 months(6 months and 12 months)
- Change from Baseline 5-hydroxyindoleacetic acetic (5-HIAAC) concentration at 12 months(Baseline and 12 months)
- Change from 6 month Serotonin (5-HT) concentration at 12 months(6 months and 12 months)
- Change from Baseline Noradrenaline concentration at 12 months(Baseline and 12 months)
- Change from 6 month 5-hydroxyindoleacetic acetic (5-HIAAC) concentration at 12 months(6 months and 12 months)
- Change from Baseline Noradrenaline concentration at 6 months(Baseline and 6 months)
研究者
Marian Zulet
Principal Investigator
University of Navarra