Resolution of Liver Fat in Non-alcoholic Fatty Liver Disease

NCT ID: NCT02558530

Last Updated: 2022-04-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2021-12-31

Brief Summary

The major adverse health consequences of obesity occur only when non-alcoholic fatty liver disease (NAFLD) also develops. NAFLD is characterized by abnormal hepatic accumulation of triglycerides and other lipids. The first-line approach to NAFLD management is caloric restriction and weight loss, but these remain difficult to achieve. Little attention has been given to dietary carbohydrate restriction, despite recent reports showing that hepatic de novo lipogenesis, a process that converts dietary carbohydrates into fatty acids in the postprandial state, accounts for approximately 25% of liver triglyceride content in hyperinsulinemic subjects with NAFLD. For comparison, only 15% of the liver triglycerides were derived from dietary fatty acids in patients with NAFLD who had consumed a standardized 30% fat diet for four days before being assessed.

Detailed Description

To establish the time-course of hepatic fat loss in NAFLD subjects on a carbohydrate-restricted diet (<20 g/day), a serial assessments of liver fat during two week diet will be performed. Also, markers of lipid and insulin metabolism, liver function test and changes in gut microbiota during rapid metabolic improvement will be assessed.

The overall aim is to exploit this unique set of human material to determine the specific cellular and molecular pathways that are modified in the early stages of metabolic improvement and fatty liver regression.

Conditions

NAFLD

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low carbohydrate diet

Isocaloric diet, \<20 g carbohydrates per day

Group Type: OTHER

Low carbohydrate diet

Intervention Type: OTHER

Isocaloric, carbohydrate restricted diet 14 days

Interventions

Low carbohydrate diet

Isocaloric, carbohydrate restricted diet 14 days

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• increased liver fat above 5 % in magnetic resonance spectroscopy
• body mass index 27-39.9 kg/m2

Exclusion Criteria

• liver cirrhosis
• portal hypertension
• chronic liver disease other than NAFLD
• diabetes mellitus or other significant endocrine disease
• any medication acting on nuclear hormone receptors or inducing liver enzymes or self-administration of supplements other than calcium or vitamins/trace elements
• any significant cardiovascular co-morbidity
• history of non-compliance
• genotype (PNPLA3-MM and TM6SF2-TT) promoting liver fat accumulation

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sahlgrenska University Hospital

OTHER

Sponsor Role: collaborator

Göteborg University

OTHER

Sponsor Role: collaborator

Helsinki University Central Hospital

OTHER

Sponsor Role: lead

Responsible Party

Marja-Riitta Taskinen

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marja-Riitta Taskinen, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Helsinki

Locations

RPU Diabetes and Obesity, Biomedicum

Helsinki, , Finland

Wllenberg Laboratory

Gothenburg, , Sweden

Countries

Finland; Sweden

References

Mardinoglu A, Wu H, Bjornson E, Zhang C, Hakkarainen A, Rasanen SM, Lee S, Mancina RM, Bergentall M, Pietilainen KH, Soderlund S, Matikainen N, Stahlman M, Bergh PO, Adiels M, Piening BD, Graner M, Lundbom N, Williams KJ, Romeo S, Nielsen J, Snyder M, Uhlen M, Bergstrom G, Perkins R, Marschall HU, Backhed F, Taskinen MR, Boren J. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans. Cell Metab. 2018 Mar 6;27(3):559-571.e5. doi: 10.1016/j.cmet.2018.01.005. Epub 2018 Feb 15.

Reference Type: DERIVED

PMID: 29456073 (View on PubMed)

Other Identifiers

Atkins

Identifier Type: -

Identifier Source: org_study_id