Non.Alcoholic Fatty Liver DiseasePhase 3NCT01623024
Effect on Liver Histology of Vitamin D in Patients With Non-alcoholic Steatohepatitis
A Phase 3 study testing Vitamin D and Lifestyle counseling in people with Non.Alcoholic Fatty Liver Disease, run by University of Palermo at 1 site in Italy.
Trial summary
Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disorders characterized by predominantly macrovesicular hepatic steatosis occurring in individuals in the absence of significant alcohol consumption. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non.Alcoholic Fatty Liver Disease
- What is being tested?
- Vitamin D and Lifestyle counseling
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2012to Sep 2014
- Phase
- Phase 3
- 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
Who may be able to join
- Patients older 18 years
- Histological diagnosis of possible or definite NASH, according to Kleiner score, within 6 months before randomization.
Who cannot join
- Average alcohol consumption exceeding 20 g per day in women and 30 g per day in men for at least 3 consecutive months during the previous 5 years, as evaluated by self-administrated questionnaires, 7-day recall tests rand confirmed by a family member.
- Other causes of chronic liver disease: Wilson's disease (normal serum ceruloplasmin); alpha-1-antitrypsin deficiency (normal serum alpha-1-antitrypsin); viral hepatitis (anti-HCV and HBsAg negativity); primary biliary cirrhosis (ANA<1:160 and AMA negativity); autoimmune hepatitis (ANA, SMA and LKM <1:160 and absence of histological features of autoimmune hepatitis); HIV infection (anti-HIV negativity); hypo or hyperthyroidism (normal TSH).
- History of or planned gastrointestinal bypass or any additional bariatric surgery/intervention.
- Hepatic cirrhosis with a Child-Pugh score of B or C, and/or concomitant hepatocellular carcinoma
- Recent significant weight loss (>5% TBW within previous 6 months)
- Recent (within 6 months of baseline liver biopsy and screening visit) or concomitant use of agents known to cause hepatic steatosis (corticosteroids, amiodarone, methotrexate, tamoxifen, tetracycline, high dose estrogens (with the exclusion of standard HRT and oral contraceptive treatment), valproic acid)
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- Recent (within 6 months of baseline liver biopsy and screening visit) change in dose/regimen or first treatment with vitamin E, Vitamin C, betaine, s-adenosyl methionine, ursodeoxycholate, sylimarin, fibrate, statin, pentoxyfilline, angiotensin II inhibitors, orlistat, sibutramine. Oral hypoglycaemic agents and insulin will be allowed, provided they had been initiated at least 6 months before enrollment and are maintained at stable doses.
- Ongoing or recent therapy (within 6 months of baseline liver biopsy and screening visit) with vitamin D or with medications known to affect vitamin D3 metabolism, including vitamin/mineral supplements.
- Any additional condition that might interfere with optimal participation in the study, according to Investigators opinion.
- Be pregnant or breastfeeding.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Sezione di Gastroenterologia, Di.Bi.M.I.S. AOUP Paolo Giaccone, University of Palermo, Italy
Palermo, Palermo, 90127
Antonio Craxì, Professor, 00390916552280, antonio.craxi@unipa.it
Antonio Craxì, Professor
About this study
Official title: A Randomised Controlled Trial of Vitamin D Plus Plus Lifestyle Versus Lifestyle in Patients With Non-alcoholic Steatohepatitis:Effect on Liver Histology and Metabolic Parameters
Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disorders characterized by predominantly macrovesicular hepatic steatosis occurring in individuals in the absence of significant alcohol consumption. In this context it is possible to distinguish a condition of simple fatty liver, where the only histologic finding is the presence of steatosis, from a state of non-alcoholic steatohepatitis (NASH), characterized by hepatocellular injury/inflammation with or without fibrosis. The prevalence of NAFLD is around 20-30% in the general population. With a rapid increase in the risk factors for metabolic syndrome, NAFLD has become the most common cause of liver disease in Western countries. The clinical relevance of NAFLD arises from the fact that a considerable proportion of subjects (20-30%) develop NASH, and this condition can progress to cirrhosis in up to 15% of patients. In addition NAFLD, and particularly NASH, represents a cardiovascular risk factor, independent of other well-known conditions contributing to heart and vascular diseases.
Lifestyle modification is the effective medical treatment recommended for NASH, while there is currently no pharmacologic therapy of proven benefit in these patients. Several pilot studies, using insulin sensitizers (thiazolidinediones or metformin), and antioxidants, like vitamin E, have provided inconclusive evidence that these drugs may improve clinical and histological features of NASH.
In the complex and not completely understood pathogenic puzzle of NAFLD and NASH, also vitamin D might have an important role. Vitamin D deficiency is associated with many common pathological conditions frequently observed in NAFLD, like cardiovascular disease, and insulin resistance. A recent paper by Targher and colleagues showed low vitamin D serum levels in NAFLD patients, identifying an inverse relation between vitamin D levels and the severity of liver disease. In keeping with the above data, recent experimental evidence also suggested the potential ability of vitamin D, through interaction with its nuclear receptor (vitamin D receptor - VDR), to interfere with inflammatory response, T cell function and fibrogenesis. Therefore considering the link between vitamin D serum levels, severity of NAFLD, and risk factors for NAFLD, we speculate that vitamin D might represent a new therapeutic target in the management of NASH patients.
- Conditions
- Non.Alcoholic Fatty Liver Disease
- Being tested
- Vitamin D, Lifestyle counseling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin DDrug
20.000 UI/week for 96 weeks
Lifestyle counselingBehavioural
Lifestyle counseling for 96 weeks
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D and Lifestyle counseling | Experimental | Not described Receives: Drug: Vitamin D |
| Lifestyle counseling | Active comparator | Not described Receives: Behavioral: Lifestyle counseling |
What is being measured
The primary outcome is the main question the study is designed to answer.
(a) improvement in NAS by at least 2 points spread across at least 2 of the NAS components or post-treatment NAS of 3 points or less, (b) at least 1 point improvement in the score for ballooning degeneration and (c) no worsening of the fibrosis score.
Measured: 96 weeks
Secondary outcomes (4)
Changes in individual components of NAS score
Measured: 96 WEEKS
Changes in intima-media thickness
Measured: 96 WEEKS
Changes in liver fibrosis
Measured: 96 weeks
Changes in insulin resistance
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2012 (estimated)
- Study startSep 2012
- Primary completionSep 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Palermo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Antonio Craxi, University of Palermo
- Investigators
- Antonio Craxì, Professor, Principal investigator, Sezione di Gastroenterologia, Di.Bi.M.I.S. University of PALERMO, ITALY
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01623024
- Sponsor's protocol ID
- NAFLD-VITAMIN D 01
- Status last verified
- Jun 2012
- First submitted
- 15 Jun 2012
- Last updated
- 21 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Targher G, Bertolini L, Scala L, Cigolini M, Zenari L, Falezza G, Arcaro G. Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. 2007 Sep;17(7):517-24. doi: 10.1016/j.numecd.2006.04.002. Epub 2006 Aug 22.
PubMed 16928437Petta S, Camma C, Scazzone C, Tripodo C, Di Marco V, Bono A, Cabibi D, Licata G, Porcasi R, Marchesini G, Craxi A. Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C. Hepatology. 2010 Apr;51(4):1158-67. doi: 10.1002/hep.23489.
PubMed 20162613von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol. 2010 Apr;11(4):344-9. doi: 10.1038/ni.1851. Epub 2010 Mar 7.
PubMed 20208539Abramovitch S, Dahan-Bachar L, Sharvit E, Weisman Y, Ben Tov A, Brazowski E, Reif S. Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats. Gut. 2011 Dec;60(12):1728-37. doi: 10.1136/gut.2010.234666. Epub 2011 Aug 4.
PubMed 21816960
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial of Vitamin D Plus Plus Lifestyle Versus Lifestyle in Patients With Non-alcoholic Steatohepatitis:Effect on Liver Histology and Metabolic Parameters
- ClinicalTrials.gov ID
- NCT01623024
- Acronym / sponsor ID
- NAFLD-VITAMIN D 01
- Conditions
- Non.Alcoholic Fatty Liver Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of PalermoUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Sep 2014 (estimated)
- First posted
- 19 Jun 2012 (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.
Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disorders characterized by predominantly macrovesicular hepatic steatosis occurring in individuals in the absence of significant alcohol consumption. In this context it is possible to distinguish a condition of simple fatty liver, where the only histologic finding is the presence of steatosis, from a state of non-alcoholic steatohepatitis (NASH), characterized by hepatocellular injury/inflammation with or without fibrosis. The prevalence of NAFLD is around 20-30% in the general population. With a rapid increase in the risk factors for metabolic syndrome, NAFLD has become the most common cause of liver disease in Western countries. The clinical relevance of NAFLD arises from the fact that a considerable proportion of subjects (20-30%) develop NASH, and this condition can progress to cirrhosis in up to 15% of patients. In addition NAFLD, and particularly NASH, represents a cardiovascular risk factor, independent of other well-known conditions contributing to heart and vascular diseases.
Lifestyle modification is the effective medical treatment recommended for NASH, while there is currently no pharmacologic therapy of proven benefit in these patients. Several pilot studies, using insulin sensitizers (thiazolidinediones or metformin), and antioxidants, like vitamin E, have provided inconclusive evidence that these drugs may improve clinical and histological features of NASH.
In the complex and not completely understood pathogenic puzzle of NAFLD and NASH, also vitamin D might have an important role. Vitamin D deficiency is associated with many common pathological conditions frequently observed in NAFLD, like cardiovascular disease, and insulin resistance. A recent paper by Targher and colleagues showed low vitamin D serum levels in NAFLD patients, identifying an inverse relation between vitamin D levels and the severity of liver disease. In keeping with the above data, recent experimental evidence also suggested the potential ability of vitamin D, through interaction with its nuclear receptor (vitamin D receptor - VDR), to interfere with inflammatory response, T cell function and fibrogenesis. Therefore considering the link between vitamin D serum levels, severity of NAFLD, and risk factors for NAFLD, we speculate that vitamin D might represent a new therapeutic target in the management of NASH patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin D and Lifestyle counseling | Experimental | Drug: Vitamin D |
| Lifestyle counseling | Active comparator | Behavioral: Lifestyle counseling |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients older 18 years
- Histological diagnosis of possible or definite NASH, according to Kleiner score, within 6 months before randomization.
Key exclusion criteria (10 listed)
- Average alcohol consumption exceeding 20 g per day in women and 30 g per day in men for at least 3 consecutive months during the previous 5 years, as evaluated by self-administrated questionnaires, 7-day recall tests rand confirmed by a family member.
- Other causes of chronic liver disease: Wilson's disease (normal serum ceruloplasmin); alpha-1-antitrypsin deficiency (normal serum alpha-1-antitrypsin); viral hepatitis (anti-HCV and HBsAg negativity); primary biliary cirrhosis (ANA<1:160 and AMA negativity); autoimmune hepatitis (ANA, SMA and LKM <1:160 and absence of histological features of autoimmune hepatitis); HIV infection (anti-HIV negativity); hypo or hyperthyroidism (normal TSH).
- History of or planned gastrointestinal bypass or any additional bariatric surgery/intervention.
- Hepatic cirrhosis with a Child-Pugh score of B or C, and/or concomitant hepatocellular carcinoma
- Recent significant weight loss (>5% TBW within previous 6 months)
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 |
|---|---|---|
| Vitamin D20.000 UI/week for 96 weeks | Drug | Vitamin D and Lifestyle counseling |
| Lifestyle counselingLifestyle counseling for 96 weeks | Behavioural | Lifestyle counseling |
Primary outcome
(a) improvement in NAS by at least 2 points spread across at least 2 of the NAS components or post-treatment NAS of 3 points or less, (b) at least 1 point improvement in the score for ballooning degeneration and (c) no worsening of the fibrosis score.
Time frame: 96 weeks
4 secondary outcomes
Changes in individual components of NAS score
Time frame: 96 WEEKS
Changes in intima-media thickness
Time frame: 96 WEEKS
Changes in liver fibrosis
Time frame: 96 weeks
Changes in insulin resistance
Time frame: 96 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2012.
- Background: PubMed 16928437Targher G, Bertolini L, Scala L, Cigolini M, Zenari L, Falezza G, Arcaro G. Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. 2007 Sep;17(7):517-24. doi: 10.1016/j.numecd.2006.04.002. Epub 2006 Aug 22.
- Background: PubMed 20162613Petta S, Camma C, Scazzone C, Tripodo C, Di Marco V, Bono A, Cabibi D, Licata G, Porcasi R, Marchesini G, Craxi A. Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C. Hepatology. 2010 Apr;51(4):1158-67. doi: 10.1002/hep.23489.
- Background: PubMed 20208539von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol. 2010 Apr;11(4):344-9. doi: 10.1038/ni.1851. Epub 2010 Mar 7.
- Background: PubMed 21816960Abramovitch S, Dahan-Bachar L, Sharvit E, Weisman Y, Ben Tov A, Brazowski E, Reif S. Vitamin D inhibits proliferation and profibrotic marker expression in hepatic stellate cells and decreases thioacetamide-induced liver fibrosis in rats. Gut. 2011 Dec;60(12):1728-37. doi: 10.1136/gut.2010.234666. Epub 2011 Aug 4.
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.
Antonio Craxì, Professor principal investigator
Sezione di Gastroenterologia, Di.Bi.M.I.S. University of PALERMO, ITALY
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitamin D and Lifestyle counseling in people with Non.Alcoholic Fatty Liver Disease, run by University of Palermo at 1 site in Italy.
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 2 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 21 Jun 2012. 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 Italy. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Antonio Craxì, MD (00390916552280, antonio.craxi@unipa.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
(a) improvement in NAS by at least 2 points spread across at least 2 of the NAS components or post-treatment NAS of 3 points or less, (b) at least 1 point improvement in the score for ballooning degeneration and (c) no worsening of the fibrosis score. (time frame: 96 weeks). 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 NCT01623024, which also lists 4 linked publications.
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 21 Jun 2012.