The Effect of Curcumin on Liver Fat Content in Obese Subjects

• Status: Completed
• Trial end date: 2020-12-16
• Target enrollment: 0
• Participant gender: Male

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Steno Diabetes Center; Steno Diabetes Center Copenhagen
• Collaborators: Herlev and Gentofte Hospital; University of Aarhus; University of Copenhagen
• Treatments: Curcumin

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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