Clinical trial NCT03222206: The Comparison of Effect Between Salsalate and Placebo in Osteoarthritis With Nonalcoholic Fatty Liver Disease
Official title: The Comparison of Effect Between Salsalate and Placebo in Osteoarthritis With Nonalcoholic Fatty Liver Disease: Investigator Initiated Randomized Placebo-controlled Double-blind, Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Non Alcoholic Fatty Liver
Osteo Arthritis
Keywords: Hepatokine
Adipokine
Saccharometabolism
Lipid metabolism
Lead sponsor: Korea University Guro Hospital
Sponsor class: OTHER
Collaborators: name: Kuhnil Pharmaceutical Co., Ltd.
First posted: 2017-07-19
Enrollment: 34
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Salsalate (2g/d), Place (2g/d)
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: Inclusion Criteria:

* Osteoarthritis patient who has non alcoholic fatty liver
* Standard of non alcoholic fatty liver diagnosis

  1. Fatty liver on abdominal ultrasonography
  2. 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

Primary outcomes:
measure: Change of controlled attenuation parameter
timeFrame: baseline and 8weeks
measure: Change of hepatokine as Fetuin-A
timeFrame: baseline and 8weeks
measure: Change of pulse wave velocity
timeFrame: baseline and 8weeks
measure: Change of adipokine as Adiponectin
timeFrame: baseline and 8weeks
Secondary outcomes:
measure: Change of controlled attenuation parameter
timeFrame: baseline and 4weeks
measure: Change of hepatokine as Fetuin-A
timeFrame: baseline and 4weeks
measure: Change of pulse wave velocity
timeFrame: baseline and 4weeks
measure: Change of adipokine as Adiponectin
timeFrame: baseline and 4weeks
measure: Numerical value change of fatty liver index
timeFrame: baseline, 4weeks and 8weeks
measure: Numerical value change of hepatic fibrosis as Nonalcoholic Fatty Liver Disease(NAFLD) fibrosis score
timeFrame: baseline, 4weeks and 8weeks
measure: 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
timeFrame: baseline, 4weeks and 8weeks
measure: Change of lipid metabolic factors as Cholesterol, Triglyceride, LDL-cholesterol HDL-cholesterol and liver function test as Aspartate Transaminase(AST) and Alanine Transaminase(ALT)
timeFrame: baseline, 4weeks and 8weeks
measure: Change of inflammatory factors as C Reactive Protein(CRP), Tumor Necrosis Factor(TNF)-a
timeFrame: baseline, 4weeks and 8weeks
measure: Change of liver fibrosis factors as hyaluronic acid
timeFrame: baseline, 4weeks and 8weeks
measure: Change of symptom of osteoarthritis as visual analog score for pain
timeFrame: baseline, 4weeks and 8weeks
measure: Change of function of osteoarthritis as WOMAC (The Western Ontario and McMaster Universities Osteoarthritis Index)
timeFrame: baseline, 4weeks and 8weeks
measure: Stability comparison like side effect
timeFrame: Up to 2month
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
Study officials:
affiliation: Associate Professor
name: Ji Hoon Kim, MD
role: PRINCIPAL_INVESTIGATOR
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