Serine Supplementation for Obese Subjects With Fatty Liver Disease
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|ClinicalTrials.gov Identifier: NCT02599038|
Recruitment Status : Completed
First Posted : November 6, 2015
Last Update Posted : October 18, 2016
|Condition or disease||Intervention/treatment||Phase|
|Non-alcoholic Fatty Liver Disease||Dietary Supplement: Serine supplementation||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Serine Supplementation in Nonalcoholic Fatty Liver Disease|
|Study Start Date :||October 2015|
|Actual Primary Completion Date :||October 2016|
|Actual Study Completion Date :||October 2016|
Experimental: Serine supplementation
Serine oral administration 20mg/kg/day
Dietary Supplement: Serine supplementation
Serine supplementation (200 mg/kg/day)
- Liver fat content [ Time Frame: 2 weeks ]Liver fat measured by magnetic resonance spectroscopy
- Triglycerides [ Time Frame: 2 weeks ]
- Cholesterol fractions [ Time Frame: 2 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02599038
|Göteborg, Sweden, 411 31|
|Principal Investigator:||Hanns-Ulrich Marschall, MD, PhD||Sahlgrenska Academy and University Hospital|