Allogenic Mesenchymal Stem Cell Intraarticular Injection for Knee Osteoarthritis Therapy

Study Overview
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Brief Summary
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This phase I and II double blinded randomized clinical controlled trial investigates the safety and efficacy of intraarticular knee injection with allogenic adipose derived mesenchymal stem cells (AD-MSC), in patients suffering from mild-moderate knee osteoarthritis compared to placebo injection with saline.

Official Title
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Allogenic Mesenchymal Stem Cell Intraarticular Injection for Knee Osteoarthritis Therapy, an RCT Explorative Mode-of-action Study

Conditions
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Knee Osteoarthritis

Intervention / Treatment
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* Biological: Allogenic adipose derived mesenchymal stem cells (AD-MSC)
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic knee pain (defined for at least 6 months with NRS 4 or above when pain worst) Patients with Grade II-III osteoarthritis according to the Kellgren Lawrence Classification and a joint width space of 1-3 mm. Axial hip, knee, ankle x-ray with no more than 5 degrees valgus/varus deformity Medial, lateral or dual compartment OA as determined above BMI <35 Danish speaker Patients must be legally competent and must be able to sign the written consent Exclusion Criteria: Severe Osteoarthritis (Grade IV according to Kellgren Lavrence Classification) Intraarticular tumor, infection or fracture Pregnancy and breast feeding Cognitive impairment Treatment with cytostatic drugs Previous intraarticular knee injection in the past 3 mo. Unable to perform MRI scan (non-compatible implants, claustrophobia and severe obesity(>BMI 35) Previous ligament reconstruction Meniscal operation with resection with more than 50% or multiple meniscal operations (more than one resection) Diabetes mellitus type 1 and 2 Knee instability and anterior-posterior laxity of 3mm or above on physical examination History of allergy to antibiotics Concomitant severe infection, malignant tumor, coagulation diseases or uncontrolled or unmanaged systemic disease Presence of other types of inflammatory arthritis

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Interventional group Single intraarticular knee injection with allogenic adipose derived mesenchymal stem cells Placebo group Single intraarticular knee injection with saline
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br>Single intraarticular knee injection with allogenic adipose derived mesenchymal stem cells (AD-MSC) 20 million AD-MSC in 10 mL saline | Biological: Allogenic adipose derived mesenchymal stem cells (AD-MSC)<br>* Laboratory isolated, cultivated and cryopreserved allogenic adipose derived mesenchymal stem cells (AD-MSC) from health donors undergoing cometic plastic surgery will be thawed on the injection day and formulated in 10 mL saline. The AD-MSCs will then be intraarticular injected using ultrasonic guidance.<br>|
| Placebo Comparator: Control<br>Single intraarticular knee injection with saline alone 10 mL saline | Other: Saline<br>* 10 mL saline will be intraarticular injected using ultrasonic guidance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observation (change) of adverse events | Pain Diary first 30 days after treatment, any reported adverse events after treatment | Baseline, 3 months, 12 months, 24 months, 3 years, 4 years, 5 years | 
| Change in Knee symptoms (questionnaire Knee injury and Osteoarthritis Outcome Score (KOOS) (symptoms)) from baseline | (questionnaire Knee injury and Osteoarthritis Outcome Score (KOOS) (symptoms)) | Baseline, 3 months, 12 months, 24 months, 3 years, 4 years, 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pain from baseline | Numeric Rating Scale (NRS) | Baseline, 3 months, 12 months, 24 months, 3 years, 4 years, 5 years | 
| Observation (change) of cartilage regeneration compared to baseline | MRI Osteoarthritis Knee Score | Baseline, 3 months, 12 months, 24 months | 
| Observation (change) of quantitative cartilage regeneration compared to baseline | Quantitative MRI (unit: stress and strain and volumen cartilage) | Baseline, 3 months, 12 months, 24 months | 
| Improvement (change) during clinical examination with range of motion compared to baseline | Range of motion (unit: degrees) | Baseline, 3 months, 12 months, 24 months | 
| Improvement (change) during clinical examination with Effusion tests (swelling) compared to baseline | Effusion tests (swelling) (unit: effusion (YES/NO)) | Baseline, 3 months, 12 months, 24 months | 
| Improvement (change) during clinical examination with measurement of knee diameter (swelling) compared to baseline | Measure knee diameter (unit: cm) | Baseline, 3 months, 12 months, 24 months | 
| Improvement (change) during clinical examination with measurement of quadriceps muscle diameter (atrofi) compared to baseline | Measure quadriceps muscle (unit: cm) | Baseline, 3 months, 12 months, 24 months | 
| Change in HLA-typing from baseline | Bloodsample HLA-typing | Baseline, 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allogenic adipose derived mesenchymal stem cells, adipose derived mesenchymal stem cells, mesenchymal stem cells, stem cells