The Effect of Curcumin on Liver Fat Content in Obese Subjects

NCT03864783 | Completed DMC

• 1 other identifier: H-18045227
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-Alcoholic Fatty Liver Disease; Insulin Resistance; Glucose Tolerance Impaired; Obesity, Abdominal

Outcome Measures

Primary Outcomes (1)

• Curcumin's effect on steatosis

  Percentage of fat in the liver tissue measured by magnetic resonance spectroscopy

  42 days +/- 3 days

Secondary Outcomes (44)

• Curcumin's effect on concentration of total amino acids in plasma

  42 days +/- 3 days

• Curcumin's effect on plasma concentration of urea

  42 days +/- 3 days

• Curcumin's effect on urin concentration of urea

  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-2

  42 days +/- 3 days

Study Arms (2)

Curcumin (Meriva®)

EXPERIMENTAL

Meriva® 500 mg tablet (contains 100 mg curcumin) Dosage: 2 tablets twice daily for 42 days (+/- 3 days)

Dietary Supplement: Curcumin (Meriva®)

Placebo

PLACEBO COMPARATOR

Placebo. Dosage: 2 tablets twice daily to mimic Meriva® tablets.

Drug: Placebo Oral Tablet

Interventions

Curcumin (Meriva®) DIETARY_SUPPLEMENT

Experimental drug: Meriva® 500 mg tablet (contains 1 mg curcumin)

Curcumin (Meriva®)

Placebo Oral Tablet DRUG

Placebo: Contains same ingredients as Meriva®, apart from curcumin. Similar in appearance to Meriva®.

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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")

You may not qualify if:

• Use of glucose-lowering drugs, lipid-lowering drugs, warfarin, clopidogrel or non-vitamin K oral anticoagulants
• 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

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• University of Copenhagen: collaborator
• University of Aarhus: collaborator
• Herlev and Gentofte Hospital: collaborator

Study Sites (1)

Center for Clinical Metabolic Research

Hellerup, 2900, Denmark

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Insulin Resistance; Glucose Intolerance; Obesity, Abdominal

Interventions

Curcumin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperglycemia; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diarylheptanoids; Heptanes; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic

Study Officials

• Pernille H Hellmann, MD

  Center for Clinical Metabolic Research, Gentofte Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: At the end of the randomization visit, the patients will randomly be assigned to one of two interventions: 6 weeks of Meriva® (two capsules of 500 mg (corresponding to 200 mg curcumin) twice daily) or identically looking placebo (two capsules twice daily). There will be a stratification with respect to HbA1c, ensuring that if we include people with HbA1c ≥ 48 mmol/mol, they will be equally distributed in the two treatment arms.

Study Record Dates

• First Submitted: February 26, 2019
• First Posted: March 6, 2019
• Study Start: March 5, 2019
• Primary Completion: December 16, 2020
• Study Completion: December 16, 2020
• Last Updated: February 3, 2021

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)