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

'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'

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteochondral Lesion of Talus
• Intervention / Treatment: Procedure: BMS alone; Biological: BMS + Bone Marrow Aspirate Concentrate

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.

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jari Dahmen, MD, BSc; Phone Number: +31638522988; Email: j.dahmen@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BMS without BMAC	Procedure: BMS alone; 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.
Experimental: BMS with BMAC	Biological: BMS + Bone Marrow Aspirate Concentrate; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): September 2, 2024

Study Registration Dates

• First Submitted: July 10, 2020
• First Submitted That Met QC Criteria: July 14, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Actual): July 17, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: GK2019OUTBACK

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No