Effects of Anthriscus Sylvestris Leaves on Mild Knee Osteoarthritis

Effects of Oral Administration of Anthriscus Sylvestris Leaves on Mild Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Osteoarthritis (OA) is a common degenerative joint disorder that causes pain, stiffness, and functional impairment. Current treatments for OA are limited to symptom relief and have potential side effects. Anthriscus sylvestris leaves are a natural remedy that has been shown to have anti-inflammatory and cartilage-protective effects in animal models of OA.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis; Articular Cartilage; Functional Food
• Intervention / Treatment: Dietary supplement: Aqueous extract of A. sylvestris leaves; Dietary supplement: microcrystalline cellulose

Detailed Description

Osteoarthritis (OA) is a common degenerative joint disorder that causes pain, stiffness, and functional impairment. Current treatments for OA are limited to symptom relief and have potential side effects. Anthriscus sylvestris leaves are a natural remedy that has been shown to have anti-inflammatory and cartilage-protective effects in animal models of OA. A randomized, double-blind, placebo-controlled trial was conducted with 100 participants aged 40 to 75 with Kellgren & Lawrence grade 1 or 2 knee OA. Participants were assigned to receive either 500 mg of Anthriscus sylvestris leaves extract or placebo daily for 12 weeks. The primary outcome was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline to week 12. Secondary outcomes included the changes in visual analogue scale (VAS) for pain, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) from baseline to week 12. The Anthriscus sylvestris leaves extract group showed a significant improvement in the total WOMAC score, as well as the pain, stiffness, and physical function sub-scores, compared with the placebo group after 12 weeks of treatment. The Anthriscus sylvestris leaves extract group also showed a significant reduction in VAS and CRP, but not in ESR, compared with the placebo group. No adverse events or safety concerns were reported in either group. Anthriscus sylvestris leaves extract enhanced joint and cartilage health in humans with mild OA symptoms, as indicated by the reduction in WOMAC, VAS, and CRP. The extract was also safe and well-tolerated. Anthriscus sylvestris leaves extract may be a promising natural alternative for the management and prevention of OA.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seo-gu
    • Busan, Seo-gu, Korea, Republic of, 49241
      • Pusan National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults aged 40 to 75 years, regardless of gender
• Individuals with a Visual Analogue Scale (VAS) score of 3/10 or higher
• Individuals with a Kellgren & Lawrence grading scale of grade 1 or 2, determined by 'Both Knee Joint AP/LAT' radiographs
• Individuals who have had a washout period of at least 4 weeks for arthritis- related medications or health supplements
• Individuals capable of normal physical activity who have voluntarily provided written informed consent to participate in this study

Exclusion Criteria:

• Individuals with a history of fractures within the past year
• Individuals with osteophytes around the joints, irregular joint surfaces, or subchondral bone cysts, indicating moderate arthritis
• Individuals currently undergoing treatment for a diagnosed thyroid disorder
• Individuals with kidney disease or serum creatinine levels of 1.4 mg/dL or higher
• Individuals with proteinuria of 2+ or higher
• Individuals with liver disease or AST or ALT levels of 100 IU/L or higher
• Individuals with uncontrolled hypertension or heart conditions such as angina or myocardial infarction
• Individuals taking medication for psychiatric disorders, except for intermittent medication for sleep disorders
• Individuals who have taken herbal or medicinal decoctions within the past two months
• Individuals who have received other investigational drugs within the past four weeks
• Individuals who need to continuously take medication that may affect the outcome of the study
• Individuals with a history of gastrointestinal resection surgery (excluding appendectomy)
• Pregnant or breastfeeding women
• Individuals with alcoholism or those who drink more than four times per week regularly
• Individuals with hypersensitivity to the test food or its ingredients
• Individuals who may be uncooperative or deemed incapable of completing the study by the investigator
• Individuals with arthritis due to specific factors other than degeneration, as determined by the principal investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; The intervention group consumed the test food twice daily (400 mg in the morning and 400 mg in the evening, each time as one hard capsule), 30 minutes after eating, with water. The administration period lasted 12 weeks for each participant. The test food is named Aqueous extract of A. sylvestris leaves. The ingredients and their contents are as follows: Aqueous extract of A. sylvestris leaves 62.5%, Microcrystalline Cellulose 35.5%, Silicon Dioxide 1.0%, Magnesium Stearate 1.0%. The dosage form is a hard capsule, with a content weight of 400 mg per capsule.	Dietary supplement: Aqueous extract of A. sylvestris leaves; Provided functional food made from Aqueous extract of A. sylvestris leaves
Placebo Comparator: Control Group; The Control group consumed the test food twice daily (400 mg in the morning and 400 mg in the evening, each time as one hard capsule), 30 minutes after eating, with water. The administration period lasted 12 weeks for each participant. The test food is named Microcrystalline Cellulose. The ingredients and their contents are as follows: Microcrystalline Cellulose 98%, Silicon dioxide 1.0%, Magnesium stearate 1.0%. The dosage form is a hard capsule, with a content weight of 400 mg per capsule.	Dietary supplement: microcrystalline cellulose; Provided placebo composed of microcrystalline cellulose instead of A. sylvestris leaf extract.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC(Western Ontario and Mcmasters Universities)	The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was assessed through a survey, with scores ranging from 0 to 96. Higher scores indicate worse outcomes.	Visit 2 (baseline) and Visit 3 (during the trial, 4week±7day) and Visit 4 (end of the trial) (12week±7day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS(Visual Analogue Scale)	The Visual Analogue Scale (VAS) was assessed through a survey, with scores ranging from 0 to 100. Higher scores indicate worse outcomes.	Visit 2 (baseline) and Visit 3 (during the trial, 4week±7day) and Visit 4 (end of the trial) (12week±7day)
Anti-inflammatory indicator	Concentration of C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) were measured from blood samples collected from the Jeonju vein after fasting for 8 hours and analyzed in our hospital's laboratory.	Visit 1 (screening) and Visit 3 (during the trial, 4week±7day) and Visit 4 (end of the trial) (12week±7day)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Blood pressure was measured in a sitting position after resting using BP-203 RVII(Colin Corp, Aichi, Japan).	Visit 1 (screening) Visit 2 (baseline) and Visit 3 (during the trial, 4week±7day) and Visit 4 (end of the trial) (12week±7day)
Body weight	Body weight in kilograms were measured using a digital scale and stadiometer (BSM370, Biospace Co Ltd, Seoul).	Visit 1 (screening)
Height	Height in meters were measured using a digital scale and stadiometer (BSM370, Biospace Co Ltd, Seoul).	Visit 1 (screening)
Gathering subject information from the survey	All participants received information on demographics, history (diagnosis or drug treatment of hypertension, diabetes or dyslipidemia), health-related habits (smoking, drinking and alcohol), and medications taken through the survey. Participants were defined as non-smokers, past smokers, and current smokers, and non-smokers (0 to 98 g/week) or drinkers who drink an average of 7 cups of men and 5 or more cups of women twice per person.	Visit 1 (screening)
Assessment of Bilateral Knee Joint Degeneration using AP/LAT Radiographs	Assessment of Bilateral Knee Joint Degeneration using AP/LAT Radiographs: Radiographic evaluation of bilateral knee joints will be performed using anterior-posterior (AP) and lateral (LAT) views. X-ray equipment in the hospital will be used to obtain these images. The degree of joint degeneration will be measured and reported based on established radiographic criteria, including the Kellgren-Lawrence grading scale.	Visit 1 (screening)
Presence of Hepatitis B Surface Antigen (HbsAg)	At Visit 1, the presence of Hepatitis B Surface Antigen (HbsAg) was tested through blood analysis.	Visit 1 (screening)
Presence of Hepatitis C Virus Antibodies (Anti-HCV)	At Visit 1, the presence of Hepatitis C Virus Antibodies (Anti-HCV) was tested through blood analysis.	Visit 1 (screening)
Presence of Human Chorionic Gonadotropin (HCG) in Urine	At Visit 1, the presence of HCG in urine was tested for all females of reproductive age, excluding males and postmenopausal women.	Visit 1 (screening)
Blood Glucose Level	Blood glucose level was measured from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening) and Visit 3 (during the trial, 4week±7day) Visit 4 (end of the trial) (12week±7day)
Complete Blood Count (CBC)	CBC was analyzed from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening) and Visit 3 (during the trial, 4week±7day) Visit 4 (end of the trial) (12week±7day)
Blood Urea Nitrogen (BUN) Level	BUN level was measured from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening) and Visit 3 (during the trial, 4week±7day) Visit 4 (end of the trial) (12week±7day)
Serum Creatinine Level	Serum creatinine level was measured from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening) and Visit 3 (during the trial, 4week±7day) Visit 4 (end of the trial) (12week±7day)
Estimated Glomerular Filtration Rate (GFR)	GFR was estimated from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening) and Visit 3 (during the trial, 4week±7day) Visit 4 (end of the trial) (12week±7day)
Total Cholesterol Level	Total cholesterol level was measured from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening) and Visit 3 (during the trial, 4week±7day) Visit 4 (end of the trial) (12week±7day)
Urine pH	The pH level of urine was measured at Visit 1 (screening) using a dipstick method.	Visit 1 (screening)
Urine Specific Gravity	The specific gravity of urine was measured at Visit 1 (screening) using a refractometer.	Visit 1 (screening)
Urine Protein	The protein level in urine was measured at Visit 1 (screening) using a dipstick method.	Visit 1 (screening)
Urine Glucose	The glucose level in urine was measured at Visit 1 (screening) using a dipstick method.	Visit 1 (screening)
Urine Ketones	The ketone level in urine was measured at Visit 1 (screening) using a dipstick method.	Visit 1 (screening)
Urine Blood	The presence of blood in urine was measured at Visit 1 (screening) using a dipstick method.	Visit 1 (screening)
Urine Leukocytes	The presence of leukocytes in urine was measured at Visit 1 (screening) using a dipstick method.	Visit 1 (screening)
Aspartate Aminotransferase (AST)	Aspartate Aminotransferase (AST) levels were measured using blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
Alanine Aminotransferase (ALT)	Alanine Aminotransferase (ALT) levels were measured using blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
Alkaline Phosphatase (ALP)	Alkaline Phosphatase (ALP) levels were measured using blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
Gamma-Glutamyl Transferase (GGT)	Gamma-Glutamyl Transferase (GGT) levels were measured using blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
Total Bilirubin	Total Bilirubin levels were measured using blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
Serum Sodium (Na)	Serum Sodium (Na) levels were measured from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
Serum Potassium (K)	Serum Potassium (K) levels were measured from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
Serum Chloride (Cl)	Serum Chloride (Cl) levels were measured from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
C-Reactive Protein (CRP)	C-Reactive Protein (CRP) levels were measured from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
Erythrocyte Sedimentation Rate (ESR)	Erythrocyte Sedimentation Rate (ESR) levels were measured from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
Triglycerides	Triglyceride levels were analyzed from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
High-Density Lipoprotein (HDL)	HDL levels were analyzed from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)
Low-Density Lipoprotein (LDL)	LDL levels were analyzed from blood samples (12 cc) collected after fasting for 8 hours.	Visit 1 (screening), Visit 3 (during the trial, 4 weeks ±7 days), Visit 4 (end of the trial, 12 weeks ±7 days)

Collaborators and Investigators

• Sponsor: Pusan National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2019
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: July 14, 2024
• First Submitted That Met QC Criteria: July 31, 2024
• First Posted (Actual): August 2, 2024

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: H-1905-043-079

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No