Resolution of Liver Fat in Non-alcoholic Fatty Liver Disease

• ClinicalTrials.gov Identifier: NCT02558530
• Recruitment Status: Completed
• First Posted: September 24, 2015
• Last Update Posted: April 12, 2022
• Sponsor: Helsinki University Central Hospital
• Collaborators: Sahlgrenska University Hospital, Sweden; Göteborg University
• Information provided by (Responsible Party): Marja-Riitta Taskinen, Helsinki University Central Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
NAFLD	Other: Low carbohydrate diet	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Rapid Resolution of Human Fatty Liver Disease, the Key to Obesity-related Morbidity and Mortality
• Actual Study Start Date: January 2015
• Actual Primary Completion Date: April 2021
• Actual Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Low carbohydrate diet; Isocaloric diet, <20 g carbohydrates per day	Other: Low carbohydrate diet; Isocaloric, carbohydrate restricted diet 14 days

Outcome Measures

Primary Outcome Measures :

1. Liver fat percent by nuclear magnetic resonance imaging [ Time Frame: 14 days ]
   Liver fat percent measured by nuclear magnetic resonance imaging

Secondary Outcome Measures :

1. De novo lipogenesis measured as Incorporation of new fatty acids (%) to very-low density lipoprotein triglycerides [ Time Frame: 14 days ]
2. Gut microbiota measured as change in microbiome profile from baseline [ Time Frame: 14 days ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Finland

RPU Diabetes and Obesity, Biomedicum

Helsinki, Finland

Sweden

Wllenberg Laboratory

Gothenburg, Sweden

Sponsors and Collaborators

Helsinki University Central Hospital

Sahlgrenska University Hospital, Sweden

Göteborg University

Investigators

• Principal Investigator: Marja-Riitta Taskinen, Professor; University of Helsinki

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Marja-Riitta Taskinen, Professor, Helsinki University Central Hospital
• ClinicalTrials.gov Identifier: NCT02558530
• Other Study ID Numbers: Atkins
• First Posted: September 24, 2015
• Last Update Posted: April 12, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Digestive System Diseases