Osteochondral Lesions Under 15mm2 of the Talus; is Iliac Crest Bone Marrow Aspirate Concentrate the Key to Success?

Study Overview
=================
Brief Summary
-----------------
Osteochondral defects (OCDs) of the talus have a significant impact on the quality of life of patients. When OCDs are of small nature (up to 15 mm in diameter), and have failed conservative management, surgical intervention may be necessary. For small cystic defects the current treatment is an arthroscopic bone marrow stimulation (BMS) procedure, during which the damaged cartilage is resected and the subchondral bone is microfractured (MF), in order to disrupt intraosseous blood vessels and thereby introduce blood and bone marrow cells into the debrided lesion, forming a microfracture fibrin clot, which contains a dilute stem cell population from the underlying bone marrow. This procedure has been reported to have a 75% successful long-term outcome. Recently, the additional use of biological adjuncts has become popular, one of them being bone marrow aspirate concentrate (BMAC) from the iliac crest. BMAC consists of mesenchymal stem cells, hematopoietic stem cells and growth factors, which may therefore theoretically improve the quality of subchondral plate and cartilage repair. The current evidence for treating talar OCDs with BMS plus BMAC is limited and heterogeneous. It is unclear to what extent the treatment of talar OCDs with BMS plus BMAC is beneficial in comparison to BMS alone.

Detailed Description
-----------------
Osteochondral defects (OCDs) of the talus have a significant impact on the quality of life of patients. When OCDs are of small nature (up to 15 mm in diameter), and have failed conservative management, surgical intervention may be necessary. For small cystic defects the current treatment is an arthroscopic bone marrow stimulation (BMS) procedure, during which the damaged cartilage is resected and the subchondral bone is microfractured (MF), in order to disrupt intraosseous blood vessels and thereby introduce blood and bone marrow cells into the debrided lesion, forming a microfracture fibrin clot, which contains a dilute stem cell population from the underlying bone marrow. This procedure has been reported to have a 75% successful long-term outcome. Recently, the additional use of biological adjuncts has become popular, one of them being bone marrow aspirate concentrate (BMAC) from the iliac crest. BMAC consists of mesenchymal stem cells, hematopoietic stem cells and growth factors, which may therefore theoretically improve the quality of subchondral plate and cartilage repair. The current evidence for treating talar OCDs with BMS plus BMAC is limited and heterogeneous. It is unclear to what extent the treatment of talar OCDs with BMS plus BMAC is beneficial in comparison to BMS alone.

Official Title
-----------------
'A Randomized Clinical Trial on the Clinical Efficacy of Bone Marrow Stimulation Combined With the Insertion of Bone Marrow Aspirate Concentrate (BMAC) for the Treatment of Small Primary and Non-primary Talar Osteochondral Lesions'

Conditions
-----------------
Osteochondral Lesion of Talus

Intervention / Treatment
-----------------
* Biological: BMS + Bone Marrow Aspirate Concentrate
* Procedure: BMS alone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with a symptomatic OCL of the talus who are scheduled for arthroscopic debridement and microfracture OCL depth and/or diameter ≤ 15 mm on computed tomography medial-lateral and/or anterior-posterior Age 18 years or older Intact remaining articular cartilage of the joint Kellgren-Lawrence stage 0-1 Exclusion Criteria: Concomitant OCL of the tibia Ankle osteoarthritis grade 2 or 3 van Dijk et al. [53] Ankle fracture < 6 months before scheduled arthroscopy Inflammatory arthropathy (e.g Rheumatoid arthritis) History of (or current) hemopoeitic disease or immunotherapy Acute or chronic instability of the ankle Use of prescribed orthopaedic shoewear Other concomitant painful or disabling disease of the lower limb Pregnancy Implanted pacemaker Participation in previous trials < 1 year, in which the subject has been exposed to radiation (radiographs or CT) Patients who are unable to fill out questionnaires and cannot have them filled out No informed consent HIV positive or hepatitis B or C infection (based on the anamnesis of the patient)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BMS without BMAC<br> | Procedure: BMS alone<br>* Both groups of patients are surgically treated with arthroscopic bone marrow stimulation (BMS). The control group will receive BMS alone but with a sham-treatment consisting of a Jamashidi (bone marrow aspiration) needle puncture of the iliac crest. The aspirated bone marrow concentrate will be collected and sent for cell characterisation but will not be inserted in the talar OCD. The intervention group will also receive arthroscopic BMS. From this group, BMAC from the iliac crest will be taken by the same needle puncture. Part of this concentrate will be sent for cell characterisation. Another part will be implanted into the talar OCD.<br>|
| Experimental: BMS with BMAC<br> | Biological: BMS + Bone Marrow Aspirate Concentrate<br>* Both groups of patients are surgically treated with arthroscopic bone marrow stimulation (BMS). The control group will receive BMS alone but with a sham-treatment consisting of a Jamashidi (bone marrow aspiration) needle puncture of the iliac crest. The aspirated bone marrow concentrate will be collected and sent for cell characterisation but will not be inserted in the talar OCD. The intervention group will also receive arthroscopic BMS. From this group, BMAC from the iliac crest will be taken by the same needle puncture. Part of this concentrate will be sent for cell characterisation. Another part will be implanted into the talar OCD.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Rating Scale of Pain During Weightbearing |  | 2 years post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EQ5D |  | pre-operatively | 
| EQ5D |  | three months postoperatively | 
| EQ5D |  | one-year post-operatively | 
| EQ5D |  | two years post-operatively | 
| AOFAS | American Orthopaedic Foot and Ankle Score (AOFAS) | preoperatively | 
| AOFAS | American Orthopaedic Foot and Ankle Score (AOFAS) | three months postoperatively | 
| AOFAS | American Orthopaedic Foot and Ankle Score (AOFAS) | one-year post-operatively | 
| AOFAS | American Orthopaedic Foot and Ankle Score (AOFAS) | two years post-operatively | 
| FAOS | Foot and Ankle Outcome Score | pre-operatively | 
| FAOS | Foot and Ankle Outcome Score | three months | 
| FAOS | Foot and Ankle Outcome Score | one-year post-operatively | 
| FAOS | Foot and Ankle Outcome Score | two years post-operatively | 
| NRS in rest | Numeric Rating Scale of Pain During Rest | pre-operatively | 
| NRS in rest | Numeric Rating Scale of Pain During Rest | 3 months postoperatively | 
| NRS in rest | Numeric Rating Scale of Pain During Rest | 1 year postoperatively | 
| NRS in rest | Numeric Rating Scale of Pain During Rest | 2 years postoperatively | 
| NRS during running | Numeric Rating Scale of Pain During Running | pre-operatively | 
| NRS during running | Numeric Rating Scale of Pain During Running | 3 months postoperatively | 
| NRS during running | Numeric Rating Scale of Pain During Running | 1 year postoperatively | 
| NRS during running | Numeric Rating Scale of Pain During Running | 2 years postoperatively | 
| NRS during stair-climbing | Numeric Rating Scale of Pain During Stair-Climbing | pre-operatively | 
| NRS during stair-climbing | Numeric Rating Scale of Pain During Stair-Climbing | 3 months postoperatively | 
| NRS during stair-climbing | Numeric Rating Scale of Pain During Stair-Climbing | 1 year postoperatively | 
| NRS during stair-climbing | Numeric Rating Scale of Pain During Stair-Climbing | 2 years postoperatively | 
| NRS during performing sports | Numeric Rating Scale of Pain During Sports | pre-operatively | 
| NRS during performing sports | Numeric Rating Scale of Pain During Sports | 3 months post-operatively | 
| NRS during performing sports | Numeric Rating Scale of Pain During Sports | 1 year post-operatively | 
| NRS during performing sports | Numeric Rating Scale of Pain During Sports | 2 years post-operatively | 
| NRS during weight-bearing | Numeric Rating Scale of Pain During Weightbearing | pre-operatively | 
| NRS during weight-bearing | Numeric Rating Scale of Pain During Weightbearing | 3 months postoperatively | 
| NRS during weight-bearing | Numeric Rating Scale of Pain During Weightbearing | 1 year post-operativley | 
| FAAM | Foot and Ankle Ability Measure | pre-operatively | 
| FAAM | Foot and Ankle Ability Measure | 3 months postoperatively | 
| FAAM | Foot and Ankle Ability Measure | 1 year postoperatively | 
| FAAM | Foot and Ankle Ability Measure | 2 years postoperatively | 
| SF-12 | Short-Form 12 | pre-operatively | 
| SF-12 | Short-Form 12 | 3 months postoperatively | 
| SF-12 |  | 1 year postoperatively | 
| SF-12 | Short-Form 12 | 2 years postoperatively | 
| Ankle Activity Scale (AAS) |  | pre-operatively | 
| Ankle Activity Scale (AAS) |  | 3 months postoperatively | 
| Ankle Activity Scale (AAS) |  | 1 year post-operatively | 
| Ankle Activity Scale (AAS) |  | 2 year post-operatively | 
| Return to sports |  | post-operatively until 2 years of follow-up post-operatively | 
| Return to work |  | post-operatively until 2 years of follow-up post-operatively | 
| Radiological outcomes: CT-scan (depth, wide, length, joint space measurement) |  | pre-operatively | 
| Radiological outcomes: CT-scan (depth, wide, length, joint space measurement) |  | 2 weeks postoperatively | 
| Radiological outcomes: CT-scan (depth, wide, length, joint space measurement) |  | 1 year postoperatively | 
| Radiological outcomes: CT-scan (depth, wide, length, joint space measurement) |  | 2 years postoperatively | 
| Radiological outcomes: MRI scan (T2 relaxation times) |  | Pre-operatively | 
| Radiological outcomes: MRI scan (T2 relaxation times) |  | 1 year post-operatively | 
| Radiological outcomes: MRI scan (T2 relaxation times) |  | 2 years post-operatively | 
| Cost-effectiviness | all relevant clinical costs will be scored through a patient diary | From per-operatively to post-operatively at 2 years (one period) | 
| Cell-subset analysis | protein analyses will be performed by Sanquin | per-operatively | 
| Demographic data | all kinds of demographic data will be assessed (age, gender, etc.) | Pre-operatively | 
| Complications | all types of complications | From per-operatively to post-operatively at 2 years (one period) | 
| Re-operations | re-operations will be assessed | From per-operatively to post-operatively at 2 years (one period) |