Effect on Liver Histology of Vitamin D in Patients With Non-alcoholic Steatohepatitis

This study is not yet open for participant recruitment.
Verified June 2012 by University of Palermo
Sponsor:
Information provided by (Responsible Party):
Antonio Craxi, University of Palermo
ClinicalTrials.gov Identifier:
NCT01623024
First received: June 15, 2012
Last updated: June 20, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Non.Alcoholic Fatty Liver Disease
Drug: Vitamin D
Behavioral: Lifestyle counseling
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Palermo:

Primary Outcome Measures:
  • (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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Changes in individual components of NAS score [ Time Frame: 96 WEEKS ] [ Designated as safety issue: Yes ]
  • Changes in intima-media thickness [ Time Frame: 96 WEEKS ] [ Designated as safety issue: Yes ]
  • Changes in liver fibrosis [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]
  • Changes in insulin resistance [ Time Frame: 96 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: September 2012
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vitamin D and Lifestyle counseling Drug: Vitamin D
20.000 UI/week for 96 weeks
Active Comparator: Lifestyle counseling Behavioral: Lifestyle counseling
Lifestyle counseling for 96 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients older 18 years
  2. Histological diagnosis of possible or definite NASH, according to Kleiner score, within 6 months before randomization.

Exclusion Criteria:

  1. 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.
  2. 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).
  3. History of or planned gastrointestinal bypass or any additional bariatric surgery/intervention.
  4. Hepatic cirrhosis with a Child-Pugh score of B or C, and/or concomitant hepatocellular carcinoma
  5. Recent significant weight loss (>5% TBW within previous 6 months)
  6. 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)
  7. 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.
  8. 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.
  9. Any additional condition that might interfere with optimal participation in the study, according to Investigators opinion.
  10. Be pregnant or breastfeeding.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01623024

Contacts
Contact: Antonio Craxì, MD 00390916552280 antonio.craxi@unipa.it

Locations
Italy
Sezione di Gastroenterologia, Di.Bi.M.I.S. AOUP Paolo Giaccone, University of Palermo, Italy Not yet recruiting
Palermo, Italy, 90127
Contact: Antonio Craxì, Professor    00390916552280    antonio.craxi@unipa.it   
Principal Investigator: Antonio Craxì, Professor         
Sponsors and Collaborators
University of Palermo
Investigators
Principal Investigator: Antonio Craxì, Professor Sezione di Gastroenterologia, Di.Bi.M.I.S. University of PALERMO, ITALY
  More Information

Publications:
Responsible Party: Antonio Craxi, Full Professor of Gastroenterology, University of Palermo
ClinicalTrials.gov Identifier: NCT01623024     History of Changes
Other Study ID Numbers: NAFLD-VITAMIN D 01
Study First Received: June 15, 2012
Last Updated: June 20, 2012
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Additional relevant MeSH terms:
Fatty Liver
Fatty Liver, Alcoholic
Liver Diseases
Digestive System Diseases
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Vitamin D
Ergocalciferols
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 17, 2014