Non-alcoholic Fatty Liver DiseasePhase 1/2NCT02599038
Serine Supplementation for Obese Subjects With Fatty Liver Disease
A Phase 1/2 study testing Serine supplementation in people with Non-alcoholic Fatty Liver Disease, run by Hanns-Ulrich Marschall at 2 sites in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease
- What is being tested?
- Serine supplementation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesSweden
- Study dates
- Oct 2015to Oct 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Hanns-Ulrich Marschall
Gothenburg, 411 31
Sahlgrenska Academy
Gothenburg
About this study
Official title: Serine Supplementation in Nonalcoholic Fatty Liver Disease
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.
Read the 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
- Being tested
- Serine supplementation
- Keywords
- NAFLD, NASH, Serine, Glutathione
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Serine supplementationDietary supplement
Serine supplementation (200 mg/kg/day)
| Study group | Role | What they receive |
|---|---|---|
| Serine supplementation | Experimental | Serine oral administration 20mg/kg/day Receives: Dietary Supplement: Serine supplementation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver fat content
Liver fat measured by magnetic resonance spectroscopy
Measured: 2 weeks
Secondary outcomes (2)
Triglycerides
Measured: 2 weeks
Cholesterol fractions
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2015 (estimated)
- Study startOct 2015
- Primary completionOct 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hanns-Ulrich Marschall
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Hanns-Ulrich Marschall, Sahlgrenska University Hospital
- Investigators
- Hanns-Ulrich Marschall, MD, PhD, Principal investigator, Sahlgrenska Academy and University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02599038
- Sponsor's protocol ID
- Serine-NAFLD
- Status last verified
- Oct 2016
- First submitted
- 3 Nov 2015
- Last updated
- 18 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serine Supplementation in Nonalcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT02599038
- Acronym / sponsor ID
- Serine-NAFLD
- Conditions
- Non-alcoholic Fatty Liver Disease
- Keywords
- NAFLD, NASH, Serine, Glutathione
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Hanns-Ulrich MarschallUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 6 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Serine supplementation | Experimental | Dietary Supplement: Serine supplementationSerine oral administration 20mg/kg/day |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Serine supplementationSerine supplementation (200 mg/kg/day) | Dietary supplement | Serine supplementation |
Primary outcome
Liver fat content
Time frame: 2 weeks
Liver fat measured by magnetic resonance spectroscopy
2 secondary outcomes
Triglycerides
Time frame: 2 weeks
Cholesterol fractions
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hanns-Ulrich Marschall, MD, PhD principal investigator
Sahlgrenska Academy and University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Serine supplementation in people with Non-alcoholic Fatty Liver Disease, run by Hanns-Ulrich Marschall at 2 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver fat content (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2016.