Non-alcoholic Fatty Liver DiseasePhase 2NCT01056133
Effect of Fish-oil on Non-alcoholic Steatohepatitis (NASH)
A Phase 2 study testing Omega-3 capsules-Fish Oil in people with Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis, run by Johane Allard at 1 site in Canada.
Trial summary
The purpose of this study is to determine the effect of Omega-3 Fish oil supplementation on hepatic gene expression in patients with Non Alcoholic Steatohepatitis (NASH). In addition, effects of fish oil on intestinal microbiota will be assessed. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis
- What is being tested?
- Omega-3 capsules-Fish Oil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2009to Aug 2015
- Phase
- Phase 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with biopsy-proven NASH; male and female; age 18-65 years; BMI ≤ 40 kg/m2, alcohol consumption <20g/d; non-smokers; if known to have hyperlipidemia or diabetes, need to be stable drug regimen.
Who cannot join
- Liver disease of other etiology; documented HIV infection, anticipated need for liver transplantation in one year or complications such as recurrent variceal bleeding, spontaneous portosystemic encephalopathy, ascites or jaundice; concurrent medical illnesses, abnormal coagulation or other reasons judged by the hepatologist to contraindicate a liver biopsy; chronic gastrointestinal diseases, previous gastrointestinal surgery modifying the anatomy, patients with diabetes requiring insulin; medications known to precipitate steatohepatitis in the 6 months prior to entry; regular intake of non-steroidal anti-inflammatory drugs, regular intake of antioxidant vitamin or omega-3/fish oil supplements, prebiotics, probiotics, antibiotics, or laxatives; ursodeoxycholic acid or any experimental drug in the 6 months prior to study entry; smokers; pregnancy or lactating; female subjects who are not surgically sterile or postmenopausal and who are not using medically acceptable methods of birth control during the trial and for 30 days after the treatment period.
Trial locations and contacts
1 site in 1 country.
Canada1 site
University Health Network, Toronto General Hospital
Toronto, Ontario, M5G 1Z5
About this study
Official title: A Pilot Study to Determine the Effect of Omega-3 Polyunsaturated Fatty Acids From Fish Oil on Patients With Non-Alcoholic Steatohepatitis (NASH)
The purpose of this study is to determine the effect of Omega-3 Fish oil supplementation on hepatic gene expression in patients with Non Alcoholic Steatohepatitis (NASH). In addition, effects of fish oil on intestinal microbiota will be assessed.
Read the detailed description
Changes in fatty acid (FA) composition within the liver may influence lipid metabolism and inflammation. This is poorly understood in humans.
Especially omega-3 FA are important: They promote FA oxidation over storage and are important for export of lipids from the liver. Omega-3 FA have also anti-inflammatory properties.
Changes in liver FA composition may be influenced by dietary intake, high rate of lipid peroxidation (LP) or low delta-6 desaturase enzyme activity. We and others recently showed that NASH patients had lower hepatic n-3 and n-6 polyunsaturated FA (PUFA) with increased lipid peroxidation and low antioxidant status when compared to patients with minimal findings on liver biopsy. The dietary intake of FA was similar among the 3 groups suggesting that the difference in hepatic FA composition may be related to high lipid peroxidation or low delta-6 desaturase activity. This difference in hepatic FA composition may be of significance in the pathogenesis of NASH since it may change gene expressions in regard to lipid metabolism.
This pilot study in NASH to assess the effect of n-3 PUFA supplementation on FA composition (liver and red blood cells), hepatic gene expression, and histology. We will also assess the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) in liver and red blood cells (RBC). Oxidative stress, insulin resistance and nutritional measurements will be performed to further characterize these patients.
New research suggests that the composition of the gut flora (intestinal microbiota) may play a role in the development of NASH. The effect of fish oil on the intestinal microbiota has not been examined in humans. Therefore, intestinal microbiota is also measured before and after intervention and associations between changes in microbiota and changes in liver histology will be examined. In addition, bacterial products (short chain fatty acids in stool, lipopolysaccharide in plasma, bacterial DNA in plasma), and plasma choline will be measured. An environmental questionnaire will capture factors that can influence the intestinal microbiota.
- Being tested
- Omega-3 capsules-Fish Oil
- Keywords
- non-alcoholic fatty liver disease, non-alcoholic steatohepatitis
- 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.
Omega-3 capsules-Fish OilOther
Also called Product Name: Amber 40/20 Ethyl ester (EE), 1000 mg capsules (lemon-lime flavor), Product Code: 4020PB1000CT
Patients will take 2 capsules (1.0 g each) of n-3 PUFA (0.82/0.44 g of EPA/DHA) daily x 12 months. Since n-3 PUFA supplementation can be a potential treatment for NASH and since BMI will be< 30 kg/m2 for all subjects, patients will be told to keep their lifestyle, diet and medication stable (unless medically necessary) for the study duration in order to minimize environmental effect on gene expression.
| Study group | Role | What they receive |
|---|---|---|
| Omega-3 capsules-Fish Oil | Experimental | Omega-3 fatty acids in the form of fish oil capsules (2g/d) Receives: Other: Omega-3 capsules-Fish Oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver histology
Liver histology will be assessed for diagnosis of NASH (steatosis, inflammation, ballooning, fibrosis, mallory bodies, Non-alcoholic fatty liver disease activity score (NAS)
Measured: Baseline, 12 months
Secondary outcomes (6)
Plasma and RBC fatty acid composition and PC:PE ratio
Measured: At 3,6,12 months
Blood biochemistry (blood sugar control, lipid profile, liver enzymes)
Measured: Baseline, 6, 12 months
Intestinal microbiota
Composition of intestinal microbiota will be measured in stool samples using Ion Torrent technology and quantitative reverse transcription polymerase chain reaction
Measured: Baseline, 6, 12 months
Plasma endotoxin
Measured: Baseline, 6, 12 months
Plasma free choline
Measured: Baseline, 6, 12 months
Bacterial DNA in plasma
Measured: Baseline, 6, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2010 (estimated)
- Study startOct 2009
- Primary completionJan 2015
- Study completionAug 2015
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johane Allard
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), American College of Gastroenterology
- Responsible party
- Sponsor-investigator, Johane Allard, University Health Network, Toronto
- Investigators
- Johane P Allard, MD, FRCPC, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01056133
- Sponsor's protocol ID
- 08-0874-A
- Other IDs
- CIHR Grant#89705, MOP-123459
- Status last verified
- May 2016
- First submitted
- 22 Jan 2010
- Last updated
- 12 May 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Determine the Effect of Omega-3 Polyunsaturated Fatty Acids From Fish Oil on Patients With Non-Alcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT01056133
- Acronym / sponsor ID
- 08-0874-A
- Keywords
- non-alcoholic fatty liver disease, non-alcoholic steatohepatitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Johane AllardUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), American College of Gastroenterology
- Study start
- Oct 2009
- Primary completion
- Jan 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 26 Jan 2010 (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.
The purpose of this study is to determine the effect of Omega-3 Fish oil supplementation on hepatic gene expression in patients with Non Alcoholic Steatohepatitis (NASH). In addition, effects of fish oil on intestinal microbiota will be assessed.
Detailed description
Changes in fatty acid (FA) composition within the liver may influence lipid metabolism and inflammation. This is poorly understood in humans.
Especially omega-3 FA are important: They promote FA oxidation over storage and are important for export of lipids from the liver. Omega-3 FA have also anti-inflammatory properties.
Changes in liver FA composition may be influenced by dietary intake, high rate of lipid peroxidation (LP) or low delta-6 desaturase enzyme activity. We and others recently showed that NASH patients had lower hepatic n-3 and n-6 polyunsaturated FA (PUFA) with increased lipid peroxidation and low antioxidant status when compared to patients with minimal findings on liver biopsy. The dietary intake of FA was similar among the 3 groups suggesting that the difference in hepatic FA composition may be related to high lipid peroxidation or low delta-6 desaturase activity. This difference in hepatic FA composition may be of significance in the pathogenesis of NASH since it may change gene expressions in regard to lipid metabolism.
This pilot study in NASH to assess the effect of n-3 PUFA supplementation on FA composition (liver and red blood cells), hepatic gene expression, and histology. We will also assess the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) in liver and red blood cells (RBC). Oxidative stress, insulin resistance and nutritional measurements will be performed to further characterize these patients.
New research suggests that the composition of the gut flora (intestinal microbiota) may play a role in the development of NASH. The effect of fish oil on the intestinal microbiota has not been examined in humans. Therefore, intestinal microbiota is also measured before and after intervention and associations between changes in microbiota and changes in liver histology will be examined. In addition, bacterial products (short chain fatty acids in stool, lipopolysaccharide in plasma, bacterial DNA in plasma), and plasma choline will be measured. An environmental questionnaire will capture factors that can influence the intestinal microbiota.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Omega-3 capsules-Fish Oil | Experimental | Other: Omega-3 capsules-Fish OilOmega-3 fatty acids in the form of fish oil capsules (2g/d) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with biopsy-proven NASH; male and female; age 18-65 years; BMI ≤ 40 kg/m2, alcohol consumption <20g/d; non-smokers; if known to have hyperlipidemia or diabetes, need to be stable drug regimen.
Key exclusion criteria (1 listed)
- Liver disease of other etiology; documented HIV infection, anticipated need for liver transplantation in one year or complications such as recurrent variceal bleeding, spontaneous portosystemic encephalopathy, ascites or jaundice; concurrent medical illnesses, abnormal coagulation or other reasons judged by the hepatologist to contraindicate a liver biopsy; chronic gastrointestinal diseases, previous gastrointestinal surgery modifying the anatomy, patients with diabetes requiring insulin; medications known to precipitate steatohepatitis in the 6 months prior to entry; regular intake of non-steroidal anti-inflammatory drugs, regular intake of antioxidant vitamin or omega-3/fish oil supplements, prebiotics, probiotics, antibiotics, or laxatives; ursodeoxycholic acid or any experimental drug in the 6 months prior to study entry; smokers; pregnancy or lactating; female subjects who are not surgically sterile or postmenopausal and who are not using medically acceptable methods of birth control during the trial and for 30 days after the treatment period.
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 |
|---|---|---|
| Omega-3 capsules-Fish OilAlso: Product Name: Amber 40/20 Ethyl ester (EE), 1000 mg capsules (lemon-lime flavor), Product Code: 4020PB1000CTPatients will take 2 capsules (1.0 g each) of n-3 PUFA (0.82/0.44 g of EPA/DHA) daily x 12 months. Since n-3 PUFA supplementation can be a potential treatment for NASH and since BMI will be< 30 kg/m2 for all subjects, patients will be told to keep their lifestyle, diet and medication stable (unless medically necessary) for the study duration in order to minimize environmental effect on gene expression. | Other | Omega-3 capsules-Fish Oil |
Primary outcome
Liver histology
Time frame: Baseline, 12 months
Liver histology will be assessed for diagnosis of NASH (steatosis, inflammation, ballooning, fibrosis, mallory bodies, Non-alcoholic fatty liver disease activity score (NAS)
6 secondary outcomes
Plasma and RBC fatty acid composition and PC:PE ratio
Time frame: At 3,6,12 months
Blood biochemistry (blood sugar control, lipid profile, liver enzymes)
Time frame: Baseline, 6, 12 months
Intestinal microbiota
Time frame: Baseline, 6, 12 months
Plasma endotoxin
Time frame: Baseline, 6, 12 months
Plasma free choline
Time frame: Baseline, 6, 12 months
Bacterial DNA in plasma
Time frame: Baseline, 6, 12 months
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 12 May 2016.
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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.
Johane P Allard, MD, FRCPC principal investigator
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Omega-3 capsules-Fish Oil in people with Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis, run by Johane Allard at 1 site in Canada.
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 1 inclusion and 1 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 12 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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 phase mean?
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 histology (time frame: Baseline, 12 months). 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 12 May 2016.