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Serine Supplementation for Obese Subjects With Fatty Liver Disease

Primary Purpose

Non-alcoholic Fatty Liver Disease

Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
Serine supplementation
Sponsored by
Hanns-Ulrich Marschall
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Non-alcoholic Fatty Liver Disease focused on measuring NAFLD, NASH, Serine, Glutathione

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Hanns-Ulrich Marschall
  • Sahlgrenska Academy

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Serine supplementation

Arm Description

Serine oral administration 20mg/kg/day

Outcomes

Primary Outcome Measures

Liver fat content
Liver fat measured by magnetic resonance spectroscopy

Secondary Outcome Measures

Triglycerides
Cholesterol fractions

Full Information

First Posted
November 3, 2015
Last Updated
October 15, 2016
Sponsor
Hanns-Ulrich Marschall
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1. Study Identification

Unique Protocol Identification Number
NCT02599038
Brief Title
Serine Supplementation for Obese Subjects With Fatty Liver Disease
Official Title
Serine Supplementation in Nonalcoholic Fatty Liver Disease
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Completed
Study Start Date
October 2015 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Hanns-Ulrich Marschall

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Fatty Liver Disease
Keywords
NAFLD, NASH, Serine, Glutathione

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Serine supplementation
Arm Type
Experimental
Arm Description
Serine oral administration 20mg/kg/day
Intervention Type
Dietary Supplement
Intervention Name(s)
Serine supplementation
Intervention Description
Serine supplementation (200 mg/kg/day)
Primary Outcome Measure Information:
Title
Liver fat content
Description
Liver fat measured by magnetic resonance spectroscopy
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Triglycerides
Time Frame
2 weeks
Title
Cholesterol fractions
Time Frame
2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hanns-Ulrich Marschall, MD, PhD
Organizational Affiliation
Sahlgrenska Academy and University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hanns-Ulrich Marschall
City
Göteborg
ZIP/Postal Code
411 31
Country
Sweden
Facility Name
Sahlgrenska Academy
City
Göteborg
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No

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Serine Supplementation for Obese Subjects With Fatty Liver Disease

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