Adipose-tissue-derived Total-Stromal-cells (TOST) Therapy in Knee Osteoarthritis

Outcomes of Single Intra-articular Injection of Adipose-tissue-derived Total-Stromal-cells (TOST) Therapy in Knee Osteoarthritis

In this phase II Randomized Clinical Trial (RCT), impacts of a single Intra-articular injection of autologous adipose tissue derive total-stromal-cells (TOST) on knee pain, physical function, stiffness, and cartilage thickness assessed and compared changes before and after intervention.

Individuals with knee osteoarthritis (KOA) diagnosed by using the American College of Rheumatology (ACR) criteria for Osteoarthritis knee were included in the study. Kellgren-Lawrence (KL) radiological scores were used to define radiological changes and high-frequency musculoskeletal ultrasonogram (MSUS) was used to measure cartilage thickness.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis Knees
• Intervention / Treatment: Biological: Adipose Tissue derived Total-Stromal-Cells (TOST)

Detailed Description

A phase II randomized clinical trial (RCT) was performed with primary Knee osteoarthritis (KOA) attended in the department of physical medicine and rehabilitation, BSMMU, between January 2018 and December 2021. Approval was obtained from the institutional review board of BSMMU for this clinical trial (Reference No: BSMMU/2018/25, dated 01/01/2018). Impacts of a single intra-articular (IA) injection of autologous adipose tissue derived total-stromal-cells (TOST) containing mesenchymal stem cells on pain, physical function, stiffness, and cartilage thickness assessed and compared before and after intervention. Patients satisfied the American College of Rheumatology (ACR) criteria for osteoarthritis (OA) knee included in the study. Kellgren-Lawrence (KL) radiological scores were used to define OA grade; however, high-frequency musculoskeletal ultrasonogram (MSUS) was used to measure cartilage thickness. There is no standard protocol to follow while assessing cartilage thickness; however, recent work of Podlipska and co-workers would be a worth consideration for using adipose tissue for cartilage regeneration. As medial tibio-femoral joint is the most commonly involved in KOA, here, we consider medial femoral cartilage thickness. The assessment used a commercially available ultrasound device (Samsung Accuvix, 2010, origin- South Korea) with a 15 megahertz linear transducer ML6-15. The patient was positioned supine with the knee in full flexion. A proximal-distal probe sweeping over the anterior-central knee area, medial femoral articular cartilage imaged in an axial plane. Degenerated cartilage signified either loss of surface sharpness or increased inner echogenicity; local or total thinning of articular cartilage. The definitions for articular cartilage degeneration are as follows: Grade 0 - a monotonous anechoic band with sharp hyperechoic anterior and posterior interfaces, Grade 1 - loss of the average sharpness of cartilage interfaces and or increased echogenicity of the cartilage, Grade 2a - grade 1 plus thinning of articular cartilage less than 50%, Grade 2b - more than 50% but less than 100% thinning of articular cartilage, Grade 3 -100% local loss of the cartilage tissue.

A total of thirty KOA was randomly divided into two groups - case and control. Both groups received conventional care for KOA (acetaminophen 1 gram thrice daily for 14 days, quadriceps strengthening exercises, aerobic exercise, mind-body, proprioception, mechanical diagnosis, and therapy (MDT) exercises, and activities of daily living (ADL) modifications4, 18-20. Fifteen received six milliliters (ml) single-dose of autologous adipose tissue derived total-stromal-cells (TOST) and 3 ml activated PRP). PRP was activated with 0.1 ml calcium gluconate per 0.9 ml of PRP (1:9 ratio). However, no orthobiological product was given in another fifteen participants.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • Bangabandhu Sheikh Mujib Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary KOA with KL-grade II and III radiological changes

Exclusion Criteria:

• KOA received IA steroid, viscosupplementation, or PRP injection or undergone knee surgery within the last six months.
• Patients with septic and tubercular arthritis, post-traumatic hemarthrosis, unstable knee joint due to anterior cruciate ligament (ACL) injury, malignancy, autoinflammatory arthritis (gout), inflammatory disease (rheumatoid arthritis, psoriatic arthritis, reactive, and ankylosing spondylitis), and charcot arthropathy.
• Patients with local eczematous skin and skin infection

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adipose Tissue derived Total-Stromal-Cells (TOST); Adipose Tissue derived Total-Stromal-Cells (TOST) containing mesenchymal stem cells plus standard conservative care.	Biological: Adipose Tissue derived Total-Stromal-Cells (TOST); Single dose autologous aAdipose Tissue derived Total-Stromal-Cells (TOST) containing mesenchymal stem cell was injected in each knee of the participants having knee osteoarthritis.
No Intervention: Control; Standard Conventional Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in pain intensity	Changes in pain intensity are assessed from baseline and at week 4, 12, and 24 using Visual Analogue scale (VAS) [0-10 cm scale], where score '0' denotes no pain and 10 means worst pain.	Before treatment and after treatment at week 4, 12, and 24
Changes in Physical functioning of knee joints.	Changes in Physical functioning of knee joints were measured by The Western Ontario and McMaster Universities Arthritis Index (WOMAC). There are 17 items consist in WOMAC physical function such as Physical Function (17 items): using stairs, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on / taking off socks, rising from bed, lying in bed, getting in / out of bath, sitting, getting on / off toilet, heavy domestic duties, light domestic duties. Each item is scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The WOMAC physical score ranges between 0 and 68. The lower score means better knee functioning.	Before treatment and after treatment at week 4, 12, and 24
Changes in femoral cartilage thickness	Changes in cartilage thickness was measured from baseline to 24 weeks of the study period using high frequency ultrasound 15 MHz (6-15 MHz) transducer (Samsung Accuvix, 2010, South Korea). Mean femoral cartilage was considered for analysis	Baseline and 24 weeks after treatment

Collaborators and Investigators

• Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Collaborators: Dhaka Medical College
• Investigators: Principal Investigator: Moshiur Rahman Khasru, MBBS, FCPS, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): October 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: February 24, 2022
• First Submitted That Met QC Criteria: March 4, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 4, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Osteoarthritis, Adipose Tissue, TOST, Stem Cell
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: BSMMU/2018/25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Decision is required from all the investigators on consensus basis.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No