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

Sponsor

Korea University Guro Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03222206

Collaborator

Kuhnil Pharmaceutical Co., Ltd. (Industry)

Enrollment

Location

Arms

15.5

Actual Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Non Alcoholic Fatty Liver Osteo Arthritis	Drug: Salsalate Other: Placebo	Phase 4

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

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Salsalate (2g/d), Place (2g/d)Salsalate (2g/d), Place (2g/d)

Masking:

Double (Participant, Investigator)

Masking Description:

Double-Blind

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 8, 2017

Actual Primary Completion Date :

Feb 22, 2019

Actual Study Completion Date :

Feb 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Salsalate 17 patients received continuous medication with salsalate 2g/day after run-in period	Drug: Salsalate 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 Other Names: A03850041
Placebo Comparator: Placebo 17 patients received continuous medication with Placebo 2g/day after run-in period	Other: Placebo 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

Arm

Intervention/Treatment

Experimental: Salsalate

17 patients received continuous medication with salsalate 2g/day after run-in period

Drug: Salsalate

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

Other Names:

A03850041

Placebo Comparator: Placebo

17 patients received continuous medication with Placebo 2g/day after run-in period

Other: Placebo

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

Outcome Measures

Primary Outcome Measures

Change of controlled attenuation parameter [baseline and 8weeks]
Estimation of salsalate single injection group and placebo injection group
Change of hepatokine as Fetuin-A [baseline and 8weeks]
Estimation of salsalate single injection group and placebo injection group
Change of pulse wave velocity [baseline and 8weeks]
Estimation of salsalate single injection group and placebo injection group
Change of adipokine as Adiponectin [baseline and 8weeks]
Estimation of salsalate single injection group and placebo injection group

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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