We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Serine Supplementation for Obese Subjects With Fatty Liver Disease

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02599038
First Posted: November 6, 2015
Last Update Posted: October 18, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Hanns-Ulrich Marschall, Sahlgrenska University Hospital
  Purpose
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.

Condition Intervention Phase
Non-alcoholic Fatty Liver Disease Dietary Supplement: Serine supplementation Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Serine Supplementation in Nonalcoholic Fatty Liver Disease

Resource links provided by NLM:


Further study details as provided by Hanns-Ulrich Marschall, Sahlgrenska University Hospital:

Primary Outcome Measures:
  • Liver fat content [ Time Frame: 2 weeks ]
    Liver fat measured by magnetic resonance spectroscopy


Secondary Outcome Measures:
  • Triglycerides [ Time Frame: 2 weeks ]
  • Cholesterol fractions [ Time Frame: 2 weeks ]

Enrollment: 10
Study Start Date: October 2015
Study Completion Date: October 2016
Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Serine supplementation
Serine oral administration 20mg/kg/day
Dietary Supplement: Serine supplementation
Serine supplementation (200 mg/kg/day)

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

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


Locations
Sweden
Hanns-Ulrich Marschall
Göteborg, Sweden, 411 31
Sahlgrenska Academy
Göteborg, Sweden
Sponsors and Collaborators
Hanns-Ulrich Marschall
Investigators
Principal Investigator: Hanns-Ulrich Marschall, MD, PhD Sahlgrenska Academy and University Hospital
  More Information

Responsible Party: Hanns-Ulrich Marschall, Professor of Clinical Hepatology, Sahlgrenska University Hospital
ClinicalTrials.gov Identifier: NCT02599038     History of Changes
Other Study ID Numbers: Serine-NAFLD
First Submitted: November 3, 2015
First Posted: November 6, 2015
Last Update Posted: October 18, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Hanns-Ulrich Marschall, Sahlgrenska University Hospital:
NAFLD
NASH
Serine
Glutathione

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases