Serine Supplementation for Obese Subjects With Fatty Liver Disease

NCT ID: NCT02599038

Last Updated: 2016-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2016-10-31

Brief Summary

In this study, the investigators aim to increase the liver tissue level of GSH in NAFLD patients by short-term dietary serine supplementation and improve their liver function by lowering the oxidative stress resulting from hepatic steatosis.

Detailed Description

There is a strong correlation between major adverse health consequences of obesity and development of non-alcoholic fatty liver disease (NAFLD). NAFLD is characterized by abnormal hepatic accumulation of triglycerides and other lipids. It has become a worldwide health problem that accelerates cirrhosis, type 2 diabetes mellitus (T2DM), and especially premature cardiovascular morbidity and mortality.

The plasma level of glutathione (GSH) is typically depleted in individuals with metabolism related disorders. However, cellular GSH levels cannot be increased by supplementing GSH and it must be synthesized within the liver either de novo or by salvation pathway. The investigators found that the level of GSH is not enough to maintain and regulate the thiol redox status of the liver in subjects with high hepatic steatosis at fasting stage due to the depletion of glycine. Glycine can be synthesized via the interconversion of serine through serine hydroxymethyl transferases (SHMT1 and SHMT2) with concomitant conversion of tetrahydrofolate (THF) into 5,10-methylene-THF (CH2-THF). It has been shown that the serine synthesis is downregulated in patients with NAFLD and supplementation of serine has attenuated alcoholic fatty liver by enhancing homocysteine metabolism in mice and rats.

In this study, the investigators aim to increase the liver tissue level of GSH in NAFLD patients by short-term dietary serine supplementation and improve their liver function by lowering the oxidative stress resulting from hepatic steatosis.

Ten obese patients (BMI 30 - 39.9 kg/m2) with ultrasound and CT-verified non-alcoholic fatty liver disease (NAFLD). Subjects will be recruited from the Swedish CArdioPulmonary bioImage Study (SCAPIS) in Gothenburg. The participants in this study (50-65-year-old men and women) are randomly recruited from the Swedish Population and Address Register. Currently, 1050 subjects have been analyzed and 5000 additional subjects will be analyzed over the next 2 years. By January 2015, over 2000 subjects have been analyzed. Each subject is extensively phenotyped over two days. This includes extensive blood samples, anthropometry, carotid and liver ultrasound, and a CT examination that includes coronary calcium score, CT angiography of coronary arteries, thoracic aorta, and assessment of epicardial fat, liver fat, and subcutaneous abdominal fat.

Preliminary analysis of the first 1050 subjects indicates that approximately 20% fulfill the criteria for NAFLD, consistent with data in other western populations.

Conditions

Non-alcoholic Fatty Liver Disease

Study Design

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

Study Groups

Serine supplementation

Serine oral administration 20mg/kg/day

Group Type: EXPERIMENTAL

Serine supplementation

Intervention Type: DIETARY_SUPPLEMENT

Serine supplementation (200 mg/kg/day)

Interventions

Serine supplementation

Serine supplementation (200 mg/kg/day)

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• BMI 30 - 39.9 kg/m2; stable weight (+/- 2 kg) within the last six months
• Sex Males, pre-, and post-menopausal females
• Women of childbearing potential can only be included if a safe and reliable contraception is used, e.g., oral contraceptives
• Diagnosis NAFLD established by both liver CT and ultrasound
• Consent Patients should have given their written consent to participate in this study

Exclusion Criteria

• Chronic liver disease other than NAFLD (viral hepatitis, autoimmune liver disease, hemochromatosis, homozygous alpha1-antitrypsin deficiency and Wilson disease)
• Previous gastric or small bowel surgery
• Inflammatory bowel disease
• Uncontrolled diabetes mellitus (fasting blood glucose >6.7 mmol/L), hypothyroidism or hyperthyroidism, or other significant endocrine disease. (A subject who is euthyroid on a stable replacement dose of thyroid hormone is acceptable provided the TSH is within normal range).
• Pregnancy. A urine pregnancy test will be performed the day before start of medication. Women of childbearing potential can only be included if a safe and reliable contraception is used, e.g., oral contraceptives.
• Elevations of transaminases (ALAT/ASAT) or alkaline phosphatase or bilirubin above 2xULN (upper limit of normal) the day before start of serine supplementation.
• Other serious disease, including depressive disorders treated by medication
• Patients who will not comply with the protocol.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hanns-Ulrich Marschall

OTHER

Sponsor Role: lead

Responsible Party

Hanns-Ulrich Marschall

Professor of Clinical Hepatology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Hanns-Ulrich Marschall, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Sahlgrenska Academy and University Hospital

Locations

Hanns-Ulrich Marschall

Gothenburg, , Sweden

Sahlgrenska Academy

Gothenburg, , Sweden

Countries

Sweden

Other Identifiers

Serine-NAFLD

Identifier Type: -

Identifier Source: org_study_id