Safety and Efficacy of Sahasthara ME vs Diclofenac ME for Treating Primary Knee Osteoarthritis

A Comparative Double-Blinded Randomized Study: Clinical Safety and Efficacy of Sahasthara Microemulsion Versus Diclofenac Microemulsion for Treating Primary Knee Osteoarthritis

Background: Sahasthara is a traditional Thai herbal remedy used for the anti-inflammatory treatment of the musculoskeletal system, while diclofenac sodium is one of the most topically administered anti-inflammatory drug. However, there has not been scientifically researched regarding the efficacy and safety of SHT formulated as ME.

Purpose: To assess the safety and effectiveness of Sahasthara microemulsion (SHT-ME) in comparison to a diclofenac microemulsion (DF-ME) in treating primary osteoarthritis (OA) of the knee.

Methods: A randomized, double blinded clinical trial phase II was conducted. One treatment group received 1% SHT-ME, while the other received 2% DF-ME (2 ml, 3 times per day for 28 days) on their affected knee area. All patients were followed up at 14 and 28 days. Changes in the visual analogue scale (VAS) for pain as well as 100-meter walking times, the WOMAC index scores, and a global assessment were examined for efficacy. Clinical examinations, abnormalities in laboratory tests, and the incidence of adverse events (AEs) were assessed for safety.

Study Overview

• Status: Completed
• Conditions: Primary Knee Osteoarthritis
• Intervention / Treatment: Drug: Sahasthara Microemulsion; Drug: Diclofenac Microemulsion

Detailed Description

Outpatient participants, aged between 40 - 70 years old, were recruited. They were screened for symptoms of primary knee OA at the Department of Orthopedics, Thammasat University Hospital, Pathum Thani, Thailand, between October - December 2021. A diagnosis of knee OA in this clinical trial were made with a combination of clinical and radiographic findings according to the American College of Rheumatology (ACR). Inclusion criteria for participants were those who had a pain score higher than 30 mm out of 100 mm on the visual analog scale (VAS), experiencing moderate to severe pain intensity from OA in one or both knees (patients who affected by knee OA bilaterally were evaluated, which more severely affected knee was included in the study) and had OA grade 1 to 3 (moderate/medium degree of pain) according to the Kellgren-Lawrence classification grading scale for OA severity. The subjects would be excluded if they: 1) had a history of hypersensitivity to ingredients in SHT ME or DF-ME, 2) were pregnant or breast feeding, 3) had previous surgery knee replacement or intra-articular steroid injections within 3 months of inclusion in the study, 4) were having any coexisting musculoskeletal diseases (including rheumatoid arthritis, septic arthritis, metabolic arthritis, gout, pseudogout, and traumatic arthritis ) or dermatologic disorder which affected the surrounding skin of the knees, or 5) was assessed by body mass index (BMI) more than 32 kg/m2. The participants who were accepted to enroll in the study signed an informed consent.

Following enrollment, eligible patients were given a washout period of one week with no administration of analgesics before being randomly assigned to receive one of the treatments daily for 4 weeks. A randomized code number from a non-stratified randomization list generated by computer was used. The physicians, researchers, and statisticians were blinded from the allocation of patients involved in the trial. During the study, they were instructed not to use other analgesics, including injection drugs or other medications. Following the baseline visit, patients returned to the study site after 2 and 4 weeks for follow-up assessments of safety, efficacy and study protocol compliance.

In the trial, demographic data, clinical signs and symptoms, physical examination, visual analogue scale (VAS) for pain, 100-meter walk times, the WOMAC index scores (pain, physical function, stiffness), and laboratory tests (fasting blood sugar, lipid profile, liver function tests (AST, ALT, ALP), and renal function tests (BUN, creatinine clearance)) were collected as baseline data and as study data on day 14 and on day 28

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Pathum Thani
    • Klong Luang, Pathum Thani, Thailand, 12120
      • Thammasat University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• who had a pain score higher than 30 mm out of 100 mm on the visual analog scale (VAS)
• experiencing moderate to severe pain intensity from OA in one or both knees (patients who affected by knee OA bilaterally were evaluated, which more severely affected knee was included in the study) and had OA grade 1 to 3 (moderate/medium degree of pain) according to the Kellgren-Lawrence classification grading scale for OA severity

Exclusion Criteria:

• had a history of hypersensitivity to ingredients in SHT ME or DF-ME
• were pregnant or breast feeding
• had previous surgery knee replacement or intra-articular steroid injections within 3 months of inclusion in the study
• were having any coexisting musculoskeletal diseases (including rheumatoid arthritis, septic arthritis, metabolic arthritis, gout, pseudogout, and traumatic arthritis ) or dermatologic disorder which affected the surrounding skin of the knees
• was assessed by body mass index (BMI) more than 32 kg/m2

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sahasthara Microemulsion; The extract of Sahasthara remedy was obtained by maceration with 95% ethanol for 3 days. The marc was re-extracted using the same process two more times. After that, the extract was filtered, concentrated using a rotary evaporator at 40 degree C and vacuum (Rotavapor R-205, Buchi, Switzerland), to gave a yield of 10.3% w/w. Finally, SHT ethanolic extract was formulated into a microemulsion with 1% (w/w) of extract and was stored in 50 ml bottles.	Drug: Sahasthara Microemulsion; All patients were instructed to treat the knee with 2 ml, 3x/day, for 28 days. Each of the patients received the same appearance of drug packaging, which was not revealed until data analysis was completed, or medical emergency conditions would require an unblinding.; Other Names: Diclofenac Microemulsion
Experimental: Diclofenac Microemulsion; DF-ME, which consists of 2% diclofenac sodium, was compounded according to the published instructions by RS Therapeutics Inc. (Canada) and stored in the same containers as SHT-ME.	Drug: Diclofenac Microemulsion; All patients were instructed to treat the knee with 2 ml, 3x/day, for 28 days. Each of the patients received the same appearance of drug packaging, which was not revealed until data analysis was completed, or medical emergency conditions would require an unblinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The WOMAC index	It is a self-administered questionnaire from the latest version of WOMAC 3.1 (the Western Ontario and McMaster Universities Osteoarthritis Index) (Haq & Davatchi, 2011; Roos et al., 1999). The patients were evaluated by the WOMAC index in terms of three domains: pain score ranged from 0 (no pain) to 4 (extreme pain); physical function score ranged from 0 (no difficulty) to 4 (the most severe difficulty); stiffness score ranged from 0 (no stiffness) to 4 (the worst stiffness).	28 days (ฺDay0, Day14, Day28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The visual analogue scale (VAS)	The pain intensity was measured using the visual analogue scale (VAS), a 100-mm line representing the continuum of pain degree, arranged into 3 levels of pain: mild = 0-30; moderate = 31-60; and maximum pain = 61-100 (Haefeli & Elfering, 2006).	28 days (ฺDay0, Day14, Day28)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
100-meter time walk	Time to walk a straight horizontal indoor distance of 100 m (100-meter time walk) and the need of the participants for taking analgesics were evaluated.	28 days (ฺDay0, Day14, Day28)
The global assessment	The global assessment on a 0-4 Likert scale (0: none, 4: excellent) was executed by the patients themselves at the last follow-up.	28 days (ฺDay0, Day14, Day28)

Collaborators and Investigators

• Sponsor: Thammasat University

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Actual): November 17, 2021
• Study Completion (Actual): December 8, 2021

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: December 24, 2023
• First Posted (Actual): December 28, 2023

Study Record Updates

• Last Update Posted (Actual): December 28, 2023
• Last Update Submitted That Met QC Criteria: December 24, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Clinical; Knee Osteoarthritis; Topical; Diclofenac; Microemulsion; Sahasthara
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Diclofenac
• Other Study ID Numbers: Ninnart Intharit 01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: During publication

Drug and device information, study documents

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