Effectiveness and Safety of Autologous ADRC for Treatment of Degenerative Damage of Knee Articular Cartilage

Study Overview
=================
Brief Summary
-----------------
Autologous adipose-derived regenerative cells (ADRC) extracted using Celution 800/CRS System (Cytori Therapeutics Inc) from a portion of the fat harvested from the patient's front abdominal wall. ADRC will be administered one-time intraarticularly. This is a single arm study with no control. All patients receive cell therapy.

Detailed Description
-----------------
Patients with verified diagnosis knee joint osteoarthritis (degenerative damage of knee articular cartilage) will undergo knee arthroscopic debridement. 28 days later patients will will undergo liposuction from front abdominal wall under local anesthesia. After that autologous ADRC will be extracted using Celution 800/CRS System (Cytori Therapeutics Inc) from harvested adipose tissue. Extracted ADRC will be administered one-time intraarticularly.

Official Title
-----------------
Effectiveness and Safety of Intraarticular Administration of Autologous Adipose-Derived Regenerative Cells for Treatment of Degenerative Damage of Knee Articular Cartilage

Conditions
-----------------
Knee Joint Osteoarthritis

Intervention / Treatment
-----------------
* Procedure: Arthroscopic surgery
* Procedure: Liposuction
* Device: ADRC isolation
* Other: Intraarticular administration of autologous ADRC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pain in the knee joint during more than a half day assessed by VAS (score more than 40 mm) At least three of the following 6 criteria: 50 years of age or older, stiffness lasting less than 30 minutes, crepitus, bony tenderness, bony enlargement, no warmth to the touch Patient is able to walk without assistance Patient is familiar with Participant information sheet Patient signed informed consent form Non-inclusion Criteria: Medical history of endoprosthetic knee replacement Medical history of lower extremity osteotomy Medical history of knee surgery (including arthroscopy) during preceding 1 year prior to enrollment Medical history of intraarticular injections during preceding 6 months prior to enrollment Secondary osteoarthritis of the knee joint: posttraumatic osteoarthritis (developed after clinically significant injury), intra-articular fractures, clinically significant varus or valgus deformities of lower limbs, septic arthritis, joint's inflammatory disorders, gout, advanced chondrocalcinosis, Paget's disease, ochronosis, acromegaly, hemochromatosis, Wilson's disease, primary synovial osteochondromatosis, osteonecrosis, hemophilia Patients prescribed for immunosuppressive treatment Medical history of systemic autoimmune and inflammatory diseases Significant weight loss (> 10% of body weight in the previous year) of unknown etiology Medical history of venous thromboembolism or estimated high risk of venous thromboembolism Patients prescribed for systemic corticosteroids or other medications treatment with proven impact on bone or cartilage tissue metabolism Clinically significant abnormalities in results of laboratory tests Any conditions limiting compliance (dementia, neuropsychiatric disease, drug and alcohol abuse etc.) Participation in other clinical trials (or administration of investigational drugs) during 3 months prior inclusion Patients with malignant tumors including postoperative period, patients receiving chemotherapy and/or radiotherapy. Patient's activated partial thromboplastin time exceeds normal levels more than 1,8 times Patients prescribed for anticoagulants treatment or patient received anticoagulants at least one hour prior lipoaspiration Medical history of heterotopic ossifications Patients prescribed for glycoprotein inhibitors treatment Exclusion Criteria: Patient's refusal from the further participation in trial Patient's refusal from compliance with the requirements of contraception during the participation in research Chronic kidney disease IV- V stages (creatinine clearance < 30 mL/min estimated by Cockroft-Gault formula) Confirmed syphilis, HIV, hepatitis B or C infections Dropout Criteria: Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADRC injection<br>Subjects will undergo liposuction under local anesthesia. Lipoaspirate will be processed to isolate and concentrate adipose-derived regenerative cells (ADRC). After ADRC isolation autologous cells suspension will be injected intraarticularly into knee joint. | Procedure: Arthroscopic surgery<br> <br> Procedure: Liposuction<br> <br> Device: ADRC isolation<br>* ADRC isolation performed using Celution 800/CRS System (Cytori Therapeutics Inc) according to manufacturer's protocol<br>Other: Intraarticular administration of autologous ADRC<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of serious adverse events (SAEs) and serious adverse reactions (SARs) | Types, probability and severity of treatment emergent serious adverse events (SAEs) and serious adverse reactions (SARs) | 4 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life monitoring | Quality of life estimated by validated questionnaires: the Short Form (36) Health Survey (SF-36), Knee Injury and Osteoarthritis Outcome Score (KOOS) | Follow up to completion (up to 24 weeks after treatment) | 
| Knee pain intensity monitoring | Knee pain intensity assessed by Visual Analogue Scale (no pain=0; maximum pain=100 mm) | Follow up to completion (up to 24 weeks after treatment) | 
| Changes in knee joint structures | Changes in knee joint structure assessed by: X-ray (joint space width, bone contour, presence of osteophytes and sclerosis); MRI (articular cartilage, osteophytes, bone marrow abnormality, meniscal integrity, synovial effusion/tissue, anterior and posterior cruciate ligaments, and medial and lateral collateral ligaments); Ultrasonography (effusion, synovial thickening or hypertrophy, cartilage parameters, vascularity, Baker's cysts, osteophytes, tendon and ligament abnormalities, meniscal changes, bursitis, erosions and panniculitis) | Follow up to completion (up to 24 weeks after treatment) | 
| Changes in knee function | Changes in knee function assessed by validated questionnaire: Knee Society Score (KSS) | Follow up to completion (up to 24 weeks after treatment) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Damage of articular cartilage, Cartilage degeneration, Intraarticular injection, ADRC, Adipose-derived regenerative cells, Adipose tissue, Stem cells