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Autologous Cartilage Implantation vs Arthroscopic Debridement (ACI)

Primary Purpose

Knee Injury, Cartilage Injury

Status
Recruiting
Phase
Not Applicable
Locations
Norway
Study Type
Interventional
Intervention
Autologous Chondrocyte Implantation
Arthroscopic Debridement
Sponsored by
University Hospital, Akershus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Knee Injury

Eligibility Criteria

18 Years - 49 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Single symptomatic lesion of the trochlea, medial or lateral femoral condyle of the knee larger than 2 cm2.
  • Cartilage lesion ICRS grade 3 or 4.
  • More than 50 % of the menisci intact.
  • Ligamentous stable knee
  • Lysholm Score < 75
  • Acceptable range of motion (5-105 degrees)

Exclusion Criteria:

  • Osteoarthritis
  • Malalignment > 5 degrees measured on HKA (hip-knee-ankle) radiographs
  • Systemic arthritis
  • Previous cartilage surgery
  • Obesity BMI > 30
  • Serious drig or alcohol abuse
  • Inability to answer questionnaires or partake in rehabilitation
  • Comorbidity that may influence surgery or rehabilitation

Sites / Locations

  • Akershus University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Autologous Chondrocyte Implantation

Arthroscopic Debridement

Arm Description

A diagnostic arthroscopy of the knee joint.The lesion is stabilized down to the subchondral bone, but not through it. Cartilage biopsy is taken from the medial femoral notch. The harvested cartilage is transported to the cell culture Laboratory and cultured for two weeks. The chondrocyte implantation: A mini-open arthrotomy is performed and the lesion is curetted down to subchondral bone, avoiding bleeding. The lesion is measured and a template of sterile aluminum foil is used to cut out a matching piece of collagen sheet which is used to contain the cells in the defect. The flap is sutured to the lesion and sealed with fibrin glue, leaving and opening at the upper part for injection of the cells. The last opening is then closed with a last stitch and fibrin glue.

The AD group will be subjected to a diagnostic arthroscopy with a full inspection of the knee joint to ensure the inclusion criteria are fulfilled. Lose bodies are removed, any meniscal pathology is addressed. Inflamed synovium is debrided. The lesion is stabilized by debridement around the edges and down to the subchondral bone using a ring curette, but not through it. Microfracture or any other cartilage treatment will not be performed. No intra-articular local anesthetics will be used due to the possible harmful effect on cartilage [41-43]. All the operating surgeons will receive proper training in the operative procedure before study start.

Outcomes

Primary Outcome Measures

The Knee Injury and Osteoarthritis Outcome Score (KOOS) Quality of Life
The KOOS is a validated patient oriented outcome measure validated to use in cartilage Research. It assesses five domains, and the Fifth domain (knee related quality of life) will be the primary endpoint in this study.

Secondary Outcome Measures

The Knee Injury and Osteoarthritis Outcome Score (KOOS) Other domains
The other four domains of the KOOS score (pain, symptoms, Activity of daily living, sport and recreational function) will act as secondary endpoints
Tegner Score
A validated knee-score to assess the Level of physical activity
Lysholm Knee Score
A condition specific knee score that assesses 8 domains: limp, locking, swelling, pain, stair climbing, use of support, instability and squatting
EQ5D
A generic measure of health status that produces a simple descriptive profile of Health status used in clinical evaluation of Health care.
Visual Analogue Scale
VAS scale for pain from 0 to 10
Range of motion
Clinical evaluation of the joint range of motion
Magnetic Resonance Imaging
A radiographic evaluation of the cartilage injury at 2 years
A Hop test
Clinical evaluation of the knees agility, validated in knee sport medicine Research.

Full Information

First Posted
December 14, 2015
Last Updated
June 29, 2022
Sponsor
University Hospital, Akershus
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1. Study Identification

Unique Protocol Identification Number
NCT02636881
Brief Title
Autologous Cartilage Implantation vs Arthroscopic Debridement
Acronym
ACI
Official Title
Focal Cartilage Defects in the Knee -A Randomized Controlled Trial Comparing Autologous Chondrocyte Implantation With Arthroscopic Debridement
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
April 2016 (Actual)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Akershus

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
82 patients aged 18-49 years with an isolated focal cartilage defect in the knee will be randomized to either receive autologous cartilage implantation or arthroscopic debridement. Both groups will then undergo a systematic physiotherapy training regime for 6-9 months. The Groups will then be compared for results, after 3, 6, 12 and 24 months, by using validated patient reported outcome scores (Lysholm, KOOS, Tegner) and EQ5D (European Quality of Life 5 dimensions) as well as clinical examination and radiological findings at 2 years (MRI).
Detailed Description
Details Focal cartilage defects in the knee - A randomized controlled trial comparing Autologous Chondrocyte Implantation with arthroscopic debridement Clinical Compare the effect of Autologous Chondrocyte Implantation (ACI) with arthroscopic debridement (AD) in patients with symptomatic full thickness knee cartilage injuries larger than 2cm2. Focal cartilage injuries in the knee might have devastating effect both in the short term and in the long term. Various surgical treatment options are available; with ACI established as a recognized treatment method for larger lesions. Meta-analysis and systematic reviews have required well-designed, long-term, multicenter studies to evaluate clinical outcomes of ACI with the use of a "no treatment" group as a control group. H0: There is no difference in KOOS QoL after ACI or AD from baseline to 24 months after surgery. H1: There is a difference in KOOS QoL after ACI or AD from baseline to 24 months after surgery. Questionnaires: KOOS, Tegner score, Lysholm score, EQ-5D, VAS (Visual analogue scale). Physical examination: range of motion and hop test. Radiology: x-ray and MRI of the knee. Primary aim: KOOS quality of life (QoL) subscore. Prospective, single-blinded parallel-group bicenter study with 2 treatment arms. Approx. 36 months inclusion and 24 months follow up. In total 5 years. 24 months. All will be invited to participate in late controls after 5 and 10 years. 2 Norwegian hospitals: Akershus University Hospital and Oslo University Hospital - Ullevål. 82 patients Inclusion: age 18-50 years old, single symptomatic cartilage defect on femoral condyle or trochlea, defect size larger than 2 cm2, defect ICRS (International Cartilage Repair Society) grade 3-4, ligamentous stable knee, range of motion 5-105°, Lysholm score < 75 and informed consent. Exclusion: Osteoarthritis, rheumatoid or other systemic arthritis, malalignment > 5° measured on x-rays, BMI > 30, comorbidities that may influence surgery or rehabilitation, pregnancy, inability to complete questionnaires or rehabilitation, serious alcohol or drug abuse, previous cartilage surgery to the chondral defect except OCD (osteochondritis dissecans)surgery. 2 treatment groups with 41 patients in each group. 3 months (± 2 weeks), 6 months (± 4 weeks), 12 months (± 6 weeks) and 24 months (± 8 weeks). All will be invited to participate in late controls after 5 and 10 years. If any unforeseen complication outside normal clinical practice occurs, the sponsor representative will be contacted as soon as possible with a parallel message to the local coordinators at the involved hospitals. During each follow up, there will be a case report form (CRF) regarding complications and safety. A 5 mL venous blood sample will be drawn on the day of operation. The blood sample will be centrifuged before serum is pipetted in a sterile tube. The serum will be analyzed at Oslo University Hospital - Rikshospitalet on the cartilage biomarker microRNA-140 (miR-140). During the open chondrocyte implantation the excess cartilage debrided from the rim of the lesion will be sent for similar microRNA-140 (miR-140) analysis. (applicable for the 41 patients in the ACI arm only) If normal distribution, aims will be analyzed using linear mixed models (LMM), and the primary aim will be performed as a post hoc test for the LMM, similar to performing a two-sample t-test. If no normal distribution, analysis will be performed using Mann-Whitney U-test. Detecting a difference of 10 in primary aim with 80% power using a standard deviation of 15. A p < 0,05 is statistically significant. This gives 37 patients in each group, adding 10% drop out meaning 41 patients in each group and 82 in total. No interim analysis will be done. Monitor at Akershus University Hospital. Inclusion of 82 patients. The end of this study is 24 months after the last included patient. Inability to include 82 patients in 3 years. May prolong the inclusion period, or add other including hospitals in the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Knee Injury, Cartilage Injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
82 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Autologous Chondrocyte Implantation
Arm Type
Active Comparator
Arm Description
A diagnostic arthroscopy of the knee joint.The lesion is stabilized down to the subchondral bone, but not through it. Cartilage biopsy is taken from the medial femoral notch. The harvested cartilage is transported to the cell culture Laboratory and cultured for two weeks. The chondrocyte implantation: A mini-open arthrotomy is performed and the lesion is curetted down to subchondral bone, avoiding bleeding. The lesion is measured and a template of sterile aluminum foil is used to cut out a matching piece of collagen sheet which is used to contain the cells in the defect. The flap is sutured to the lesion and sealed with fibrin glue, leaving and opening at the upper part for injection of the cells. The last opening is then closed with a last stitch and fibrin glue.
Arm Title
Arthroscopic Debridement
Arm Type
Sham Comparator
Arm Description
The AD group will be subjected to a diagnostic arthroscopy with a full inspection of the knee joint to ensure the inclusion criteria are fulfilled. Lose bodies are removed, any meniscal pathology is addressed. Inflamed synovium is debrided. The lesion is stabilized by debridement around the edges and down to the subchondral bone using a ring curette, but not through it. Microfracture or any other cartilage treatment will not be performed. No intra-articular local anesthetics will be used due to the possible harmful effect on cartilage [41-43]. All the operating surgeons will receive proper training in the operative procedure before study start.
Intervention Type
Procedure
Intervention Name(s)
Autologous Chondrocyte Implantation
Intervention Description
Implantation of the patients own cartilage cells in a chondral defect of the knee
Intervention Type
Procedure
Intervention Name(s)
Arthroscopic Debridement
Intervention Description
Arthroscopic diagnosis and debridement of the lesion, without cartilage therapy. Removal of lose bodies etc.
Primary Outcome Measure Information:
Title
The Knee Injury and Osteoarthritis Outcome Score (KOOS) Quality of Life
Description
The KOOS is a validated patient oriented outcome measure validated to use in cartilage Research. It assesses five domains, and the Fifth domain (knee related quality of life) will be the primary endpoint in this study.
Time Frame
up to 24 months
Secondary Outcome Measure Information:
Title
The Knee Injury and Osteoarthritis Outcome Score (KOOS) Other domains
Description
The other four domains of the KOOS score (pain, symptoms, Activity of daily living, sport and recreational function) will act as secondary endpoints
Time Frame
preop, 3, 6, 12 and 24 months.
Title
Tegner Score
Description
A validated knee-score to assess the Level of physical activity
Time Frame
preop, 3, 6, 12 and 24 months.
Title
Lysholm Knee Score
Description
A condition specific knee score that assesses 8 domains: limp, locking, swelling, pain, stair climbing, use of support, instability and squatting
Time Frame
preop, 3, 6, 12 and 24 months.
Title
EQ5D
Description
A generic measure of health status that produces a simple descriptive profile of Health status used in clinical evaluation of Health care.
Time Frame
preop, 3, 6, 12 and 24 months.
Title
Visual Analogue Scale
Description
VAS scale for pain from 0 to 10
Time Frame
preop, 3, 6, 12 and 24 months.
Title
Range of motion
Description
Clinical evaluation of the joint range of motion
Time Frame
preop, 3, 6, 12 and 24 months.
Title
Magnetic Resonance Imaging
Description
A radiographic evaluation of the cartilage injury at 2 years
Time Frame
24 months
Title
A Hop test
Description
Clinical evaluation of the knees agility, validated in knee sport medicine Research.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Single symptomatic lesion of the trochlea, medial or lateral femoral condyle of the knee larger than 2 cm2. Cartilage lesion ICRS grade 3 or 4. More than 50 % of the menisci intact. Ligamentous stable knee Lysholm Score < 75 Acceptable range of motion (5-105 degrees) Exclusion Criteria: Osteoarthritis Malalignment > 5 degrees measured on HKA (hip-knee-ankle) radiographs Systemic arthritis Previous cartilage surgery Obesity BMI > 30 Serious drig or alcohol abuse Inability to answer questionnaires or partake in rehabilitation Comorbidity that may influence surgery or rehabilitation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Per-Henrik Randsborg, PhD
Phone
+47 97040480
Email
pran@ahus.no
First Name & Middle Initial & Last Name or Official Title & Degree
Asbjorn Aaroen, Professor
Phone
+47 91587140
Email
asbjorn.aroen@medisin.uio.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heidi Hanvold, PT
Organizational Affiliation
Research coordinator
Official's Role
Principal Investigator
Facility Information:
Facility Name
Akershus University Hospital
City
Lørenskog
State/Province
Oslo
ZIP/Postal Code
0587
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Per-Henrik Randsborg, PhD MD
Phone
+4797040480
Email
pran@ahus.no
First Name & Middle Initial & Last Name & Degree
Asbjørn Årøen, PhD MD
Phone
+4791587140
Email
asbjorn.aroen@uio.no

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33913035
Citation
Banitalebi H, Owesen C, Aroen A, Tran HT, Myklebust TA, Randsborg PH. Is T2 mapping reliable in evaluation of native and repair cartilage tissue of the knee? J Exp Orthop. 2021 Apr 28;8(1):34. doi: 10.1186/s40634-021-00350-1.
Results Reference
derived
PubMed Identifier
26956476
Citation
Randsborg PH, Brinchmann J, Loken S, Hanvold HA, Aae TF, Aroen A. Focal cartilage defects in the knee - a randomized controlled trial comparing autologous chondrocyte implantation with arthroscopic debridement. BMC Musculoskelet Disord. 2016 Mar 8;17:117. doi: 10.1186/s12891-016-0969-z.
Results Reference
derived

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Autologous Cartilage Implantation vs Arthroscopic Debridement

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