Hepatitis CNCT00444002
Oxidative Stress and Fatty Acids in Hepatitis C
An observational study of Hepatitis C and Hepatic Steatosis, run by Johane Allard at 1 site in Canada.
Trial summary
Hepatitis C virus infection (HCV) is a major health concern in Canada and worldwide. Chronic HCV can cause progressive liver damage leading to inflammation, scarring and, in some cases, cirrhosis or liver cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C, Hepatic Steatosis
- How many people
- 105 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2005to Jul 2010
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with chronic Hep C infection undergoing routine pre-treatment liver biopsy
Who may be able to join
- Male and female patients, age >18 y
- Established hepatitis C infection as confirmed by positive serology and positive hepatitis C RNA in serum
- Convincing evidence of negligible alcohol consumption (<20g of ethanol per day) obtained from a detailed history, confirmed by at least one close relative
- Absence of any other possible cause for liver dysfunction.
- Undergoing routing liver biopsy (usually pre-treatment)
Who cannot join
- Findings highly suggestive of liver disease of other etiology (e.g. other viral hepatitis, auto-immune chronic hepatitis, primary biliary cirrhosis and genetic liver diseases such as hemochromatosis, alpha-1 antitrypsin deficiency, Wilsons disease and biliary obstruction)
- Anticipated need for liver transplantation in one year or complications of liver disease such as recurrent variceal bleeding, spontaneous porto- systemic encephalopathy, resistant ascites or bacterial peritonitis
- Concurrent medical illnesses contraindicating a liver biopsy (history of unexplained bleeding, hemophilia or abnormal coagulation results as per routine laboratory work-up or other reasons judged by the hepatologist to contraindicate a percutaneous liver biopsy)
- Medications known to precipitate steatohepatitis (corticosteroids, high dose estrogens, methotrexate, amiodarone, calcium channel blockers, sulfasalazine or cloxacillin) in the 6 months prior to entry
- Antioxidant vitamin or n-3 supplementation, ursodeoxycholic acid or any other experimental drug in the 6 months prior to study entry
- Pregnant or lactating
Trial locations and contacts
1 site in 1 country.
Canada1 site
University Health Network (Toronto General Hospital & Toronto Western Hospital)
Toronto, Ontario
About this study
Official title: Hepatitis C Infection With Liver Steatosis Compared to Hepatitis C Infection Without Liver Steatosis: Is There a Difference in Lipid Peroxidation and Indicators of Inflammation?
Hepatitis C virus infection (HCV) is a major health concern in Canada and worldwide. Chronic HCV can cause progressive liver damage leading to inflammation, scarring and, in some cases, cirrhosis or liver cancer. It has been shown that fat accumulation in the liver can accelerate the disease progression and is therefore a risk factor in HCV patients.
However, the exact mechanism(s) by which fat accumulation in the liver is involved in disease progression are not clear yet. It is possible that the presence of fat provides a liver susceptible to a second injurious process which leads to scarring. Candidates for this second "hit" may include insulin resistance, leading to accumulation of fat within the liver cells and secondly oxidation of these lipids. In turn, lipid peroxidation can lead to production of reactive oxygen species (unstable molecules that can damage cells) and cytokines (signal molecules that promote inflammation) resulting in more oxidative stress and liver damage.
Aim of the study is to find out, whether patients with HCV and fatty liver have increased oxidative stress and inflammation than patients with HCV without fatty liver, and whether this is associated with a different nutritional status.
Read the detailed description
Hypothesis: Patients with Hepatitis C and steatosis are more oxidatively stressed than those without steatosis. This is associated with 1) increased liver lipid peroxides and cytokines (TNF-alpha, TGF-beta); 2) altered unsaturated fat status (intake, tissue storage as measured in red blood cells); 3) reduced antioxidant status.
Objectives: To assess oxidative stress and nutritional status in patients with Hepatitis C and steatosis on liver biopsy and to compare the results to the same parameters measured in patients with Hepatitis C and no steatosis.
Measurements:
Primary outcome: Liver lipid peroxides (LPO)
Secondary outcomes:
Liver: TNF-alpha; liver pathology and immunohistochemistry for adducts of malondialdehyde (MDA), a product of lipid peroxidation (LP), alpha-smooth muscle actin (alpha-SMA), a marker of hepatic stellate cell activation; and transforming growth factor (TGF-beta), a profibrogenic cytokine involved in fibrogenesis, liver fatty acid composition (substrate for lipid peroxidation).
Oxidative stress and nutrition: Plasma lipid peroxides, plasma antioxidant vitamins, antioxidant status and power, and red blood cell fatty acid composition, 7 day food record, anthropometry.
Other measurements:
Insulin resistance parameters such as blood glucose, insulin, c-peptide, hemoglobin A1c (HbA1c) Blood lipid profile, liver enzymes (as part of standard medical assessment) Subject demographics and medical history will also be recorded.
- Conditions
- Hepatitis C, Hepatic Steatosis
- Keywords
- Hepatitis C, Steatosis, Oxidative Stress, Antioxidants, Inflammation, Fatty acids
- Medical subject headings
- Hepatitis C, Fatty Liver, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Hepatitis C - Steatosis | Patients with chronic Hep C infection undergoing liver biopsy with >=5% steatosis on liver biopsy | |
| Hepatitis C - no steatosis | Patients with chronic Hep C infection without steatosis on liver biopsy (<5% of hepatocytes involved) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lipid peroxidation (LPO) in the liver
LPO by commercially available kit
Measured: Single time point
Secondary outcomes (4)
Hepatic fatty acid composition
Fatty acid and lipid composition measured by gas chromatography and mass spectrometry
Measured: Single time point
Antioxidant power in the liver
Antioxidant power (AOP) measured by test kit
Measured: Single time point
Plasma vitamin C
Plasma vitamin C by colorimetric assay
Measured: Single time point
Tocopherols in plasma
alpha- and gamma-tocopherol in plasma by gas chromatography
Measured: Single time point
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2007 (estimated)
- Study startJul 2005
- Primary completionJul 2008
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies 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
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johane Allard
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Association of Gastroenterology
- Responsible party
- Sponsor-investigator, Johane Allard, University Health Network, Toronto
- Investigators
- Johane P Allard, MD, FRCPC, Principal investigator, University Health Network, Toronto General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00444002
- Sponsor's protocol ID
- 05-0305 AE
- Status last verified
- Jan 2014
- First submitted
- 6 Mar 2007
- Last updated
- 10 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Arendt BM, Mohammed SS, Aghdassi E, Prayitno NR, Ma DW, Nguyen A, Guindi M, Sherman M, Heathcote EJ, Allard JP. Hepatic fatty acid composition differs between chronic hepatitis C patients with and without steatosis. J Nutr. 2009 Apr;139(4):691-5. doi: 10.3945/jn.108.101782. Epub 2009 Feb 11.
PubMed 19211827
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hepatitis C Infection With Liver Steatosis Compared to Hepatitis C Infection Without Liver Steatosis: Is There a Difference in Lipid Peroxidation and Indicators of Inflammation?
- ClinicalTrials.gov ID
- NCT00444002
- Acronym / sponsor ID
- 05-0305 AE
- Conditions
- Hepatitis C, Hepatic Steatosis
- Keywords
- Hepatitis C, Steatosis, Oxidative Stress, Antioxidants, Inflammation, Fatty acids
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Johane AllardUniversity, hospital or other
- Collaborators
- Canadian Association of Gastroenterology
- Study start
- Jul 2005
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 7 Mar 2007 (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.
Hepatitis C virus infection (HCV) is a major health concern in Canada and worldwide. Chronic HCV can cause progressive liver damage leading to inflammation, scarring and, in some cases, cirrhosis or liver cancer. It has been shown that fat accumulation in the liver can accelerate the disease progression and is therefore a risk factor in HCV patients.
However, the exact mechanism(s) by which fat accumulation in the liver is involved in disease progression are not clear yet. It is possible that the presence of fat provides a liver susceptible to a second injurious process which leads to scarring. Candidates for this second "hit" may include insulin resistance, leading to accumulation of fat within the liver cells and secondly oxidation of these lipids. In turn, lipid peroxidation can lead to production of reactive oxygen species (unstable molecules that can damage cells) and cytokines (signal molecules that promote inflammation) resulting in more oxidative stress and liver damage.
Aim of the study is to find out, whether patients with HCV and fatty liver have increased oxidative stress and inflammation than patients with HCV without fatty liver, and whether this is associated with a different nutritional status.
Detailed description
Hypothesis: Patients with Hepatitis C and steatosis are more oxidatively stressed than those without steatosis. This is associated with 1) increased liver lipid peroxides and cytokines (TNF-alpha, TGF-beta); 2) altered unsaturated fat status (intake, tissue storage as measured in red blood cells); 3) reduced antioxidant status.
Objectives: To assess oxidative stress and nutritional status in patients with Hepatitis C and steatosis on liver biopsy and to compare the results to the same parameters measured in patients with Hepatitis C and no steatosis.
Measurements:
Primary outcome: Liver lipid peroxides (LPO)
Secondary outcomes:
Liver: TNF-alpha; liver pathology and immunohistochemistry for adducts of malondialdehyde (MDA), a product of lipid peroxidation (LP), alpha-smooth muscle actin (alpha-SMA), a marker of hepatic stellate cell activation; and transforming growth factor (TGF-beta), a profibrogenic cytokine involved in fibrogenesis, liver fatty acid composition (substrate for lipid peroxidation).
Oxidative stress and nutrition: Plasma lipid peroxides, plasma antioxidant vitamins, antioxidant status and power, and red blood cell fatty acid composition, 7 day food record, anthropometry.
Other measurements:
Insulin resistance parameters such as blood glucose, insulin, c-peptide, hemoglobin A1c (HbA1c) Blood lipid profile, liver enzymes (as part of standard medical assessment) Subject demographics and medical history will also be recorded.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hepatitis C - Steatosis | – | –Patients with chronic Hep C infection undergoing liver biopsy with >=5% steatosis on liver biopsy |
| Hepatitis C - no steatosis | – | –Patients with chronic Hep C infection without steatosis on liver biopsy (<5% of hepatocytes involved) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with chronic Hep C infection undergoing routine pre-treatment liver biopsy
Key inclusion criteria (5 listed)
- Male and female patients, age >18 y
- Established hepatitis C infection as confirmed by positive serology and positive hepatitis C RNA in serum
- Convincing evidence of negligible alcohol consumption (<20g of ethanol per day) obtained from a detailed history, confirmed by at least one close relative
- Absence of any other possible cause for liver dysfunction.
- Undergoing routing liver biopsy (usually pre-treatment)
Key exclusion criteria (6 listed)
- Findings highly suggestive of liver disease of other etiology (e.g. other viral hepatitis, auto-immune chronic hepatitis, primary biliary cirrhosis and genetic liver diseases such as hemochromatosis, alpha-1 antitrypsin deficiency, Wilsons disease and biliary obstruction)
- Anticipated need for liver transplantation in one year or complications of liver disease such as recurrent variceal bleeding, spontaneous porto- systemic encephalopathy, resistant ascites or bacterial peritonitis
- Concurrent medical illnesses contraindicating a liver biopsy (history of unexplained bleeding, hemophilia or abnormal coagulation results as per routine laboratory work-up or other reasons judged by the hepatologist to contraindicate a percutaneous liver biopsy)
- Medications known to precipitate steatohepatitis (corticosteroids, high dose estrogens, methotrexate, amiodarone, calcium channel blockers, sulfasalazine or cloxacillin) in the 6 months prior to entry
- Antioxidant vitamin or n-3 supplementation, ursodeoxycholic acid or any other experimental drug in the 6 months prior to study entry
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Lipid peroxidation (LPO) in the liver
Time frame: Single time point
LPO by commercially available kit
4 secondary outcomes
Hepatic fatty acid composition
Time frame: Single time point
Antioxidant power in the liver
Time frame: Single time point
Plasma vitamin C
Time frame: Single time point
Tocopherols in plasma
Time frame: Single time point
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 10 Jan 2014.
- Results publication: PubMed 19211827Arendt BM, Mohammed SS, Aghdassi E, Prayitno NR, Ma DW, Nguyen A, Guindi M, Sherman M, Heathcote EJ, Allard JP. Hepatic fatty acid composition differs between chronic hepatitis C patients with and without steatosis. J Nutr. 2009 Apr;139(4):691-5. doi: 10.3945/jn.108.101782. Epub 2009 Feb 11.
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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 General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis C and Hepatic Steatosis, 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 5 inclusion and 6 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 10 Jan 2014. 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.
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?
Lipid peroxidation (LPO) in the liver (time frame: Single time point). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00444002, which also lists 1 linked publication.
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 10 Jan 2014.