Autologous Stromal Vascular Fraction of Cells for Treatment of Knee Articular Cartilage Dystrophy

Evaluation of Safety and Effectiveness of Intraarticular Administration of Autologous Stromal Vascular Fraction of Cells for Treatment of Knee Articular Cartilage Dystrophy

Stromal vascular fraction of cells (SVF) will be extracted from lipoaspirate by enzymatic digestion. SVF will be administered in a single dose intraarticularly 4 weeks after arthroscopic debridement. All patients will receive cell therapy.This is a single arm study with no control.

Study Overview

• Status: Unknown
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Procedure: Liposuction; Other: SVF isolation; Other: Intraarticular administration of autologous SVF

Detailed Description

Patients undergone arthroscopic debridement for knee osteoarthritis will be subjected to abdominal liposuction under local anaesthesia. Harvested adipose tissue will be processed according to patent pending technology based on enzymatic digestion, washing and concentration of cell pellet in 5 ml of Hartmann's solution. Isolated SVF will be administered in a single dose into anterior part of knee joint cavity 28 days after arthroscopy.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 121359
    • Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation
  • Orenburg, Russian Federation, 460018
    • Orenburg Regional Clinical Hospital
  • Orenburg, Russian Federation, 460000
    • Orenburg City Clinical Hospital #4
  • Orenburg, Russian Federation, 460018
    • Orenburg Regional Clinical Donor Blood Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pain in the knee joint during more than a half day assessed by Visual Analog Pain Scale (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 liposuction
• 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 Cockcroft-Gault formula)
• Confirmed syphilis, HIV, hepatitis B or C infections

Dropout Criteria:

• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SVF injection; Subjects will undergo liposuction under local anesthesia. Lipoaspirate will be processed to isolate and concentrate stromal vascular fraction of cells (SVF). After SVF isolation autologous cells suspension will be injected intraarticularly into knee joint.	Procedure: Liposuction; Other: SVF isolation; SVF will be isolated according to patent pending technology based on enzymatic digestion, washing and concentration of cell pellet in 5 ml of Hartmann's solution.; Other: Intraarticular administration of autologous SVF

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee pain intensity monitoring	Knee pain intensity assessed by Visual Analog Pain Scale (no pain=0; maximum pain=100 mm)	Follow up to completion (up to 24 weeks after treatment)
Changes in knee joint structure-1	Changes in knee joint structure assessed by 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 joint structure-2	Changes in knee joint structure assessed by X-ray (joint space width, bone contour, presence of osteophytes and sclerosis)	Follow up to completion (up to 24 weeks after treatment)
Changes in knee joint structure-3	Changes in knee joint structure assessed by MRI (articular cartilage, osteophytes, bone marrow abnormality, meniscal integrity, synovial effusion/tissue, anterior and posterior cruciate ligaments, and medial and lateral collateral ligaments)	Follow up to completion (up to 24 weeks after treatment)
Quality of life monitoring-1	Quality of life estimated by validated questionnaire - the Short Form (36) Health Survey (SF-36)	Follow up to completion (up to 24 weeks after treatment)
Quality of life monitoring-2	Quality of life estimated by validated questionnaire - Knee Injury and Osteoarthritis Outcome Score (KOOS)	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)

Collaborators and Investigators

• Sponsor: Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation
• Collaborators: Orenburg Regional Clinical Blood Donor Center
• Investigators: Principal Investigator: Ilya I Eremin, MD, PhD, Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation; Center for Biomedical Technologies; Principal Investigator: Rinat G Gilmutdinov, MD, PhD, Orenburg Regional Clinical Donor Blood Center; Principal Investigator: Sergey I Gilfanov, MD, PhD, Prof, Federal State Budgetary Institution "Central Clinical Hospital with Outpatient Health Center" of the Business Administration for the President of the Russian Federation; Principal Investigator: Andrey A Averyanov, MD, PhD, Orenburg Regional Clinical Hospital; Principal Investigator: Vadim A Kopylov, MD, PhD, Orenburg City Clinical Hospital #4

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Anticipated): May 1, 2018
• Study Completion (Anticipated): November 1, 2018

Study Registration Dates

• First Submitted: June 24, 2016
• First Submitted That Met QC Criteria: July 6, 2016
• First Posted (Estimate): July 11, 2016

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 19, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Stem cells; Adipose tissue; Stromal vascular fraction; Intraarticular injection; SVF; Damage of articular cartilage; Cartilage degeneration; Adipose-derived regenerative cells (ADRC)
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: RU-ССН-03-01-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided