Effectiveness and Safety of Autologous ADRC for Treatment of Anterior Cruciate Ligament Partial Rupture

Phase 1

• Conditions: Anterior Cruciate Ligament Partial Rupture
• Interventions: Procedure: Liposuction; Device: ADRC isolation; Procedure: Arthroscopic surgery; Other: Intraarticular administration of autologous ADRC

• Registration Number: NCT02469792
• Lead Sponsor: Central Clinical Hospital w/Outpatient Health Center of Business Administration for the President of Russian Federation

Brief Summary

Autologous adipose-derived regenerative cells (ADRC) will be extracted using Celution 800/CRS System (Cytori Therapeutics Inc) from a portion of the fat harvested from the patient's front abdominal wall. Patients will undergo knee arthroscopic surgery followed by one-time intraarticular ADRC administration (directly into anterior cruciate ligament). This is a single arm study with no control. All patients receive cell therapy.

Detailed Description

Patients with verified diagnosis partial rupture of anterior cruciate ligament 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. Same day patients will undergo knee arthroscopic surgery followed by one-time intraarticular freshly isolated ADRC administration (directly into anterior cruciate ligament close to the rupture).

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2015-06-09
• Study First Submitted QC: 2015-06-09
• Study First Posted: 2015-06-11
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-19
• Last Update Posted: 2017-07-21
• Primary Completion: 2018-06
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Patient suffers from partial rupture of anterior cruciate ligament (confirmed by MRI or knee arthroscopic surgery)
• Clinically significant knee instability (positive anterior drawer test, pivot shift test, and Lachman test)
• Patient is familiar with Participant information sheet
• Patient signed informed consent form

Non-inclusion Criteria:

• Knee osteoarthritis grade III and grade IV
• Medical history of autoimmune diseases
• Patients prescribed for immunosuppressive treatment
• Contraindications to the general or local anesthesia or medical history of allergic reactions to anesthetics
• Subcompensated or decompensated forms of chronic diseases of internal organs
• 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
• 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:

• Complete anterior cruciate ligament rupture confirmed by knee arthroscopic surgery
• Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ADRC injection	ADRC isolation	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 anterior cruciated ligament.
ADRC injection	Intraarticular administration of autologous ADRC	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 anterior cruciated ligament.
ADRC injection	Arthroscopic surgery	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 anterior cruciated ligament.
ADRC injection	Liposuction	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 anterior cruciated ligament.

Primary Outcome Measures

Name	Time	Method
Number of serious adverse events (SAEs) and serious adverse reactions (SARs)	2 weeks after treatment

Secondary Outcome Measures

Name	Time	Method
Knee pain intensity monitoring	Follow up to completion (up to 24 weeks after treatment)	Knee pain intensity assessed by Visual Analogue Scale (no pain=0; maximum pain=100 mm)
Quality of life monitoring	Follow up to completion (up to 24 weeks after treatment)	Quality of life estimated by validated questionnaires: the Short Form (36) Health Survey (SF-36), Knee Injury and Osteoarthritis Outcome Score (KOOS)
Changes in knee function	Follow up to completion (up to 24 weeks after treatment)	Changes in knee function assessed by questionnaire: Knee Society Score (KSS)
Changes in knee joint structures	Follow up to completion (up to 24 weeks after treatment)	Changes in knee joint structure assessed by: 1. X-ray (joint space width, bone contour, presence of osteophytes and sclerosis); 2. MRI (articular cartilage, osteophytes, bone marrow abnormality, meniscal integrity, synovial effusion/tissue, anterior and posterior cruciate ligaments, and medial and lateral collateral ligaments); 3. Ultrasonography (effusion, synovial thickening or hypertrophy, cartilage parameters, vascularity, Baker's cysts, osteophytes, tendon and ligament abnormalities, meniscal changes, bursitis, erosions and panniculitis)

Trial Locations

Locations (1)

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; 🇷🇺 Moscow, Russian Federation