The Comparison of Effect Between Salsalate and Placebo in Osteoarthritis With Nonalcoholic Fatty Liver Disease

Study Overview
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Brief Summary
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This Study purpose to verify change of variety factors that the cause of nonalcoholic fatty liver disease and its process through salsalate injection to osteoarthritis patient who has non alcoholic fatty liver

Detailed Description
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Salsalate, the salicylic acid dimer that is one of anti-inflammatory and kind of salicylate. Aspirin(Acetylated salicylic) is known as nonsteroidal anti-inflammatory, also salsalate is widely used painkiller and anti-inflammatory without prescription in Europe and America through the long time and it was approved as osteoarthritis and rheumarthritis treatment in Korea. Especially salsalate is switched to salicylic acid(active metabolite) 15% rate lower than the same dose of aspirin (3.5g vs. 5g). Salsalate is cyclooxygenase antagonist, it make anti-inflammatory effect by hinder creation of variety inflammatory induction factors like interleukin-6, Tumor Necrosis Factor (TNF)-alpha, C-reactive protein. This anti-inflammatory reaction is known to block Nuclear Factor(NF)-kappaB gene action by hinder action of IkappaB kinase. Also salsalate was reported it has positive effect to gluco metabolism as performed role of insulin-sensitizing. Therefore, the above mechanism of salsalate was expected that it can be had positive effect to metabolic disease like diabetes and obesity, and related studies are performed considerably at present. There is no clinical trial for non alcoholic fatty acid related salsalate, and there was the animal study result that salsalate may reduce occurence of non alcoholic fatty acid and fibrosis by hinder non alcoholic fatty acid creation and inflammation mediation path. Therefore, this Study purpose to verify change of variety factors that the cause of nonalcoholic fatty liver disease and its process through salsalate injection to osteoarthritis patient who has non alcoholic fatty liver

Official Title
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The Comparison of Effect Between Salsalate and Placebo in Osteoarthritis With Nonalcoholic Fatty Liver Disease: Investigator Initiated Randomized Placebo-controlled Double-blind, Pilot Study

Conditions
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Non Alcoholic Fatty Liver, Osteo Arthritis

Intervention / Treatment
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* Drug: Salsalate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Osteoarthritis patient who has non alcoholic fatty liver Standard of non alcoholic fatty liver diagnosis Fatty liver on abdominal ultrasonography Patient who has no evidence as hepatitis B, hepatitis C, immune hepatitis, metabolic hepatitis and other chronic hepatitis Osteoarthritis patient who has never been treated Exclusion Criteria: Unsuitable on inclusion criteria Thiazolidinedione injected patient for diabetes treatment or patient who has changed injected drug last 6 month Patient who is treating nonsteroidal antiinflammatory drugs for osteoarthritis Renal dysfunction : serum creatinine level 1.5mg/dl or creatinine clearance < 60ml/min Anamnesis of gastrointestinal tract bleeding Upper 5 times(200IU/l) the normality of Aspartate Transaminase(AST), Alanine Transaminase(ALT) Pregnant or Breastfeeding Patient who has untreated malignant tumor Liver transplantation patient Patient who has liver function Child-Pugh B over Patient who has serious disease that was estimated influence to study (e.g. Congestive heart failure, Kidney failure, Chronic pancreatitis, Malignant tumor) Patients who has been injected immunomodulatory and immunosuppressant(inclusive universal corticosteroids) before 6 month enrollment or at present Patient who was judged unsuitable for study by investigator

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Salsalate (2g/d), Place (2g/d)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Salsalate<br>17 patients received continuous medication with salsalate 2g/day after run-in period | Drug: Salsalate<br>* Medicate salsalate 2g/day after run-in period Check side effect after 1 month and Control dosage (2g/day or 3g/day) Check side effect after 2 month<br>* Other names: A03850041;|
| Placebo Comparator: Placebo<br>17 patients received continuous medication with Placebo 2g/day after run-in period | Other: Placebo<br>* Medicate placebo 2g/day after run-in period Check side effect after 1 month and Control dosage (2g/day or 3g/day) Check side effect after 2 month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of controlled attenuation parameter | Estimation of salsalate single injection group and placebo injection group | baseline and 8weeks | 
| Change of hepatokine as Fetuin-A | Estimation of salsalate single injection group and placebo injection group | baseline and 8weeks | 
| Change of pulse wave velocity | Estimation of salsalate single injection group and placebo injection group | baseline and 8weeks | 
| Change of adipokine as Adiponectin | Estimation of salsalate single injection group and placebo injection group | baseline and 8weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of controlled attenuation parameter | Estimation of salsalate single injection group and placebo injection group | baseline and 4weeks | 
| Change of hepatokine as Fetuin-A | Estimation of salsalate single injection group and placebo injection group | baseline and 4weeks | 
| Change of pulse wave velocity | Estimation of salsalate single injection group and placebo injection group | baseline and 4weeks | 
| Change of adipokine as Adiponectin | Estimation of salsalate single injection group and placebo injection group | baseline and 4weeks | 
| Numerical value change of fatty liver index | Estimation of salsalate single injection group and placebo injection group | baseline, 4weeks and 8weeks | 
| Numerical value change of hepatic fibrosis as Nonalcoholic Fatty Liver Disease(NAFLD) fibrosis score | Estimation of salsalate single injection group and placebo injection group | baseline, 4weeks and 8weeks | 
| Change of saccharometabolic factors as Homeostasis Model Assessment(HOMA)-Insulin Resistance(IR), Homeostasis Model Assessment(HOMA)-B, Fasting glucose, Insulin, C-peptide, HbA1c, Glycated albumin | Estimation of salsalate single injection group and placebo injection group | baseline, 4weeks and 8weeks | 
| Change of lipid metabolic factors as Cholesterol, Triglyceride, LDL-cholesterol HDL-cholesterol and liver function test as Aspartate Transaminase(AST) and Alanine Transaminase(ALT) | Estimation of salsalate single injection group and placebo injection group | baseline, 4weeks and 8weeks | 
| Change of inflammatory factors as C Reactive Protein(CRP), Tumor Necrosis Factor(TNF)-a | Estimation of salsalate single injection group and placebo injection group | baseline, 4weeks and 8weeks | 
| Change of liver fibrosis factors as hyaluronic acid | Estimation of salsalate single injection group and placebo injection group | baseline, 4weeks and 8weeks | 
| Change of symptom of osteoarthritis as visual analog score for pain | Estimation of salsalate single injection group and placebo injection group | baseline, 4weeks and 8weeks | 
| Change of function of osteoarthritis as WOMAC (The Western Ontario and McMaster Universities Osteoarthritis Index) | Estimation of salsalate single injection group and placebo injection group | baseline, 4weeks and 8weeks | 
| Stability comparison like side effect | Estimation with treatment-related adverse events as assessed by CTCAE v4.0 | Up to 2month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatokine, Adipokine, Saccharometabolism, Lipid metabolism