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

Non Alcoholic Fatty Liver Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03222206
• Other study ID #: KUGH16353
• Status: Completed
• Phase: Phase 4
• Start date: November 8, 2017
• Est. completion date: February 22, 2019

Study information

• Verified date: August 2019
• Source: Korea University Guro Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: February 22, 2019
• Est. primary completion date: February 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non Alcoholic Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Osteo Arthritis
• Osteoarthritis

Intervention

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:
• 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

Locations

Country	Name	City	State
Korea, Republic of	Korea University Guro Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Korea University Guro Hospital	Kuhnil Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (21)

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* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of controlled attenuation parameter	Estimation of salsalate single injection group and placebo injection group	baseline and 8weeks
Primary	Change of hepatokine as Fetuin-A	Estimation of salsalate single injection group and placebo injection group	baseline and 8weeks
Primary	Change of pulse wave velocity	Estimation of salsalate single injection group and placebo injection group	baseline and 8weeks
Primary	Change of adipokine as Adiponectin	Estimation of salsalate single injection group and placebo injection group	baseline and 8weeks
Secondary	Change of controlled attenuation parameter	Estimation of salsalate single injection group and placebo injection group	baseline and 4weeks
Secondary	Change of hepatokine as Fetuin-A	Estimation of salsalate single injection group and placebo injection group	baseline and 4weeks
Secondary	Change of pulse wave velocity	Estimation of salsalate single injection group and placebo injection group	baseline and 4weeks
Secondary	Change of adipokine as Adiponectin	Estimation of salsalate single injection group and placebo injection group	baseline and 4weeks
Secondary	Numerical value change of fatty liver index	Estimation of salsalate single injection group and placebo injection group	baseline, 4weeks and 8weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change of liver fibrosis factors as hyaluronic acid	Estimation of salsalate single injection group and placebo injection group	baseline, 4weeks and 8weeks
Secondary	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
Secondary	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
Secondary	Stability comparison like side effect	Estimation with treatment-related adverse events as assessed by CTCAE v4.0	Up to 2month