The Effect of Curcumin on Liver Fat Content in Obese Subjects
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Curcumin's effect on steatosis
研究概览
简要总结
The majority of obese have non-alcoholic fatty liver disease (NALFD). Currently, no pharmacological agents are licenced for the prevention or treatment of NAFLD, and weight loss, notoriously difficult to obtain (and specially to maintain), remains the only treatment option. Interestingly, curcumin, a phenolic compound extracted from the turmeric root, has from in vitro and animal studies shown promising effects in preventing and treating NAFLD, and the sparse available human data point in the same direction; but solid human data are missing. This study will delineate the effects of curcumin when treating NAFLD in humans.
The primary aim of this study is to investigate the effect of 6 weeks of curcumin on liver fat content (assessed by magnetic resonance spectroscopy (MRS)) in obese subject with NAFLD. Additionally, a range of secondary endpoints have been chosen in order to delineate the role of NAFLD in the newly discovered liver-alpha cell axis governing circulating levels of the glucose-mobilising pancreatic alpha cell hormone glucagon and, thus, to elucidate the link between liver fat content and the risk of developing reduced glucose tolerance and type 2 diabetes (T2D). Also, the anti-inflammatory effect of curcumin will be elucidated, as inflammatory markers will be measured before and after intervention. Furthermore, the effect of curcumin will be measured by measuring the following parameters before and after intervention: Transient elastography, anthropometric measurements, body weight, appetite, food-consumption, calory balance, resting energy expenditure, gut microbiota, bioimpedance measures, visceral- and subcutaneous fat, glucose tolerance, lipids, blood pressure, pulse, liver parameters (blood-tests) and adipokines. During the oral glucose tolerance test before and after intervention, incretin hormones, glucagon, amino acids, insulin, c-peptide and urea will be measured.
详细描述
The prevalence of obesity is increasing worldwide. Obesity and its associated complications represent an enormous burden for obese individuals, their families, healthcare systems and societies. Non-alcoholic fatty liver disease (NAFLD) has emerged as a frequent and serious complication of obesity. Steatosis, the benign and potentially reversible form of NAFLD, may progress to a more severe form, non-alcoholic steatohepatitis (NASH), which can result in fibrosis and ultimately liver cirrhosis, and rarely hepatocellular carcinoma. The majority of obese have NAFLD. Currently, no pharmacological agents are licenced for the prevention or treatment of NAFLD, and weight loss, notoriously difficult to obtain (and specially to maintain), remains the only treatment option. Interestingly, curcumin, a phenolic compound extracted from the turmeric root, has from in vitro and animal studies shown promising effects in preventing and treating NAFLD, and the sparse available human data point in the same direction; but solid human data are missing. This study seeks to investigate the effects of curcumin on treating NAFLD in humans by looking at the effects of ingestion of curcumin for 6 weeks in obese subject with NAFLD on lipid, glucose and protein metabolism.
In this randomised, double-blinded, placebo-controlled trial, eligible participants will undergo baseline assessments before being randomised to receive two capsules of placebo twice daily or two capsules of curcumin (corresponding to 200 mg) twice daily for 6 weeks. In the end of the 6-week intervention periods, end-of-trial assessments (similar to baseline assessments) will be performed.
Information meeting:
Prior to any protocol-related procedures, an information meeting at Center for Clinical Metabolic Research, Gentofte Hospital, will be arranged, and subjects will be informed of the possibility of bringing a person of own choice to the visit. During this meeting, a member of the research group will explain the purpose, procedures and possible risks of the study in undisturbed and confidential surroundings. The subject will be informed that if extra time to evaluate participation is needed, a minimum of 24 hours from oral information is given until the consent and sign the informed consent form should be given is acceptable. After obtaining the informed consent, time of screening is planned. The subject will be informed that it is possible to withdraw the written consent at any time prior to or during the study.
Screening visit:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The supplier of Meriva® and placebo capsules (Indena® Aps, Milan, Italy) sends the tablets to the research department. After packaging of tablets in bags with tablets for 42 days (+7 extra tablets) and labelling of bags with a "bag number", a person not otherwise involved in the study will generate a list with a randomization number and a "bag number" using a random list generator. When an investigator enrols a participant in the study, the participant is assigned with a randomization number (in consecutive order), and the corresponding "bag number" will be handed to the participant. An emergency code will be kept at Gentofte Hospital. If a subject develops adverse events (AEs) that demand knowledge of the content of the intervention, the code may be broken.
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •BMI >30.0 kg/m2
- •Haemoglobin ≥7.5 mmol/l
- •Written informed consent
- •If the subject is known with diet treated diabetes, HbA1c has to be < 48 mmol/mol.
- •If the subject is not known diabetes, HbA1c can be <53 mmol/mol
- •Two of the following four parameters:
- •Steatosis on Fibro scan with M-probe or XL-probe (S>=1)
- •Waist circumference >94 cm
- •HbA1c>48 mmol/mol
- •FLI score >60% (see enclosure 2 "FLI score")
- •Diagnosis of steatosis on liver biopsy, ultrasound or MR-scan within the last three years and no weight loss or treatment of steatosis since diagnosis. If this inclusion criterion is fulfilled, the BMI criterion written above will not be > 30 kg/m2, but > 27 kg/m2
排除标准
- •Use of glucose-lowering drugs, lipid-lowering drugs, warfarin, clopidogrel or non-vitamin K oral anticoagulants
- •Treatment with drugs with potential steatogenic side-effects within three months prior to inclusion (e.g. tetracycline, valproic acid, systemic glucocorticoids, amiodarone, tamoxifen and methotrexate)
- •Known viral, inherited or alcoholic liver disease, or any other condition known to affect the liver (e.g. coeliac disease, Wilsons disease, cystic fibrosis, alpha-1 anti-trypsin deficiency)
- •Positive result of blood test for viral hepatitis markers
- •Intake of more than 21 units of alcohol per week, or earlier alcohol abuse
- •Frequent use of anti-inflammatory drugs
- •Nephropathy (eGFR < 60 ml/min/1.73 m² and/or urine albumin > 20 mg/L)
- •In a weight management program, or planning to change life style, alcohol habits or eating habits during the study
- •Known allergy to curcumin/turmeric
- •Claustrophobia
- •Implanted metal objects contraindicative of MRS
- •Any condition(s) or clinical or biochemical signs that the investigator think would interfere with trial participation or with the safety of the subject
- •Any regular drug treatment that cannot be discontinued for minimum 18 hours
研究组 & 干预措施
Curcumin (Meriva®)
Meriva® 500 mg tablet (contains 100 mg curcumin) Dosage: 2 tablets twice daily for 42 days (+/- 3 days)
干预措施: Curcumin (Meriva®) (Dietary Supplement)
Placebo
Placebo. Dosage: 2 tablets twice daily to mimic Meriva® tablets.
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Curcumin's effect on steatosis
时间窗: 42 days +/- 3 days
Percentage of fat in the liver tissue measured by magnetic resonance spectroscopy
次要结局
- Curcumin's effect on urin concentration of urea(42 days +/- 3 days)
- Curcumin's effect on concentration of total amino acids in plasma(42 days +/- 3 days)
- Curcumin's effect on serum concentration of free fatty acids(42 days +/- 3 days)
- Curcumin's effect on BMI (kg/m^2)(42 days +/- 3 days)
- Curcumin's effect on waist circumference (cm)(42 days +/- 3 days)
- Curcumin's effect on plasma concentration of urea(42 days +/- 3 days)
- Curcumin's effect on plasma concentration of adipokines(42 days +/- 3 days)
- Curcumin's effect on glucose plasma values during an oral glucose tolerance test for 4 hours(42 days +/- 3 days)
- Curcumin's effect on serum c-peptide levels(42 days +/- 3 days)
- Curcumin's effect on body weight in kilograms(42 days +/- 3 days)
- Curcumin's effect on serum concentration of inflammatory marker interleukin (IL)-1b(42 days +/- 3 days)
- Curcumin's effect on serum concentration of inflammatory marker IL-10(42 days +/- 3 days)
- Curcumin's effect on serum concentration of inflammatory marker IL-6(42 days +/- 3 days)
- Curcumin's effect on plasma concentration of glucagon-like peptide 1(42 days +/- 3 days)
- Curcumin's effect on plasma concentration of glucose-dependent insulinotropic peptide(42 days +/- 3 days)
- Curcumin's effect on serum insulin concentration(42 days +/- 3 days)
- Curcumin's effect on liver insulin resistance(42 days +/- 3 days)
- Curcumin's effect on waist-hip ratio(42 days +/- 3 days)
- Curcumin's effect on systolic blood pressure (mmHg)(42 days +/- 3 days)
- Curcumin's effect on gut microbiota (alpha/beta diversity)(42 days +/- 3 days)
- Curcumin's effect on subcutaneous fat (cm)(42 days +/- 3 days)
- Curcumin's effect on serum concentration of inflammatory marker IL-2(42 days +/- 3 days)
- Curcumin's effect on plasma concentration of glucagon(42 days +/- 3 days)
- Curcumin's effect on diastolic blood pressure (mmHg)(42 days +/- 3 days)
- Curcumin's effect on gut microbiota (relative abundance)(42 days +/- 3 days)
- Curcumin's effect on gut microbiota (link to phenotype of interest)(42 days +/- 3 days)
- Curcumin's effect on muscle percentage(42 days +/- 3 days)
- Curcumin's effect on fat percentage(42 days +/- 3 days)
- Curcumin's effect on plasma concentration of cholesterol(42 days +/- 3 days)
- Curcumin's effect on serumconcentration of inflammatory marker tumor necrosis factor (TNF)-alpha(42 days +/- 3 days)
- Curcumin's effect on transient elastography liver stiffness measurements (kPa)(42 days +/- 3 days)
- Curcumin's effect on fat-free mass percentage(42 days +/- 3 days)
- Curcumin's effect on body water percentage(42 days +/- 3 days)
- Curcumin's effect on prospective food consumption(42 days +/- 3 days)
- Curcumin's effect on calory balance(42 days +/- 3 days)
- Curcumin's effect on plasma concentration of alanine aminotransferase(42 days +/- 3 days)
- Curcumin's effect on transient elastography controlled attenuation parameter (CAP) value (dB/m)(42 days +/- 3 days)
- Curcumin's effect on visceral fat (cm)(42 days +/- 3 days)
- Curcumin's effect on fatt mass(42 days +/- 3 days)
- Curcumin's effect on total body water(42 days +/- 3 days)
- Curcumin's effect on food consumption(42 days +/- 3 days)
- Curcumin's effect on plasma concentration of aspartate aminotransferase(42 days +/- 3 days)
- Genetic risk markers for development of NASH(On both test days)
- Curcumin's effect on fat-free mass(42 days +/- 3 days)