Adipose-tissue-derived Total-Stromal-cells (TOST) Therapy in Knee Osteoarthritis
Primary Purpose
Osteoarthritis Knees
Status
Completed
Phase
Phase 2
Locations
Bangladesh
Study Type
Interventional
Intervention
Adipose Tissue derived Total-Stromal-Cells (TOST)
Sponsored by
About this trial
This is an interventional treatment trial for Osteoarthritis Knees focused on measuring Osteoarthritis, Adipose Tissue, TOST, Stem Cell
Eligibility Criteria
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
Sites / Locations
- Bangabandhu Sheikh Mujib Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Adipose Tissue derived Total-Stromal-Cells (TOST)
Control
Arm Description
Adipose Tissue derived Total-Stromal-Cells (TOST) containing mesenchymal stem cells plus standard conservative care.
Standard Conventional Treatment
Outcomes
Primary Outcome Measures
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.
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.
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
Secondary Outcome Measures
Full Information
NCT ID
NCT05280002
First Posted
February 24, 2022
Last Updated
March 4, 2022
Sponsor
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Collaborators
Dhaka Medical College
1. Study Identification
Unique Protocol Identification Number
NCT05280002
Brief Title
Adipose-tissue-derived Total-Stromal-cells (TOST) Therapy in Knee Osteoarthritis
Official Title
Outcomes of Single Intra-articular Injection of Adipose-tissue-derived Total-Stromal-cells (TOST) Therapy in Knee Osteoarthritis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
January 1, 2018 (Actual)
Primary Completion Date
October 31, 2021 (Actual)
Study Completion Date
December 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Collaborators
Dhaka Medical College
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis Knees
Keywords
Osteoarthritis, Adipose Tissue, TOST, Stem Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
Both clinical and high-frequency-ultrasound-scanning Assessors were blinded about the case and control.
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Adipose Tissue derived Total-Stromal-Cells (TOST)
Arm Type
Experimental
Arm Description
Adipose Tissue derived Total-Stromal-Cells (TOST) containing mesenchymal stem cells plus standard conservative care.
Arm Title
Control
Arm Type
No Intervention
Arm Description
Standard Conventional Treatment
Intervention Type
Biological
Intervention Name(s)
Adipose Tissue derived Total-Stromal-Cells (TOST)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in pain intensity
Description
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.
Time Frame
Before treatment and after treatment at week 4, 12, and 24
Title
Changes in Physical functioning of knee joints.
Description
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.
Time Frame
Before treatment and after treatment at week 4, 12, and 24
Title
Changes in femoral cartilage thickness
Description
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
Time Frame
Baseline and 24 weeks after treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Moshiur Rahman Khasru, MBBS, FCPS
Organizational Affiliation
Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bangabandhu Sheikh Mujib Medical University
City
Dhaka
Country
Bangladesh
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Decision is required from all the investigators on consensus basis.
Learn more about this trial
Adipose-tissue-derived Total-Stromal-cells (TOST) Therapy in Knee Osteoarthritis
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