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

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT04475341
• Collaborator: (none)
• Enrollment: 96
• Arms: 2
• Anticipated Duration (Months): 48

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Osteochondral Lesion of Talus	Biological: BMS + Bone Marrow Aspirate Concentrate; Procedure: BMS alone	N/A

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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'
• Anticipated Study Start Date: Sep 1, 2020
• Anticipated Primary Completion Date: Sep 1, 2024
• Anticipated Study Completion Date: Sep 2, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Numeric Rating Scale of Pain During Weightbearing [2 years post-operatively]

Secondary Outcome Measures

1. EQ5D [pre-operatively]

2. EQ5D [three months postoperatively]

3. EQ5D [one-year post-operatively]

4. EQ5D [two years post-operatively]

5. AOFAS [preoperatively]

   American Orthopaedic Foot and Ankle Score (AOFAS)

6. AOFAS [three months postoperatively]

   American Orthopaedic Foot and Ankle Score (AOFAS)

7. AOFAS [one-year post-operatively]

   American Orthopaedic Foot and Ankle Score (AOFAS)

8. AOFAS [two years post-operatively]

   American Orthopaedic Foot and Ankle Score (AOFAS)

9. FAOS [pre-operatively]

   Foot and Ankle Outcome Score

10. FAOS [three months]

    Foot and Ankle Outcome Score

11. FAOS [one-year post-operatively]

    Foot and Ankle Outcome Score

12. FAOS [two years post-operatively]

    Foot and Ankle Outcome Score

13. NRS in rest [pre-operatively]

    Numeric Rating Scale of Pain During Rest

14. NRS in rest [3 months postoperatively]

    Numeric Rating Scale of Pain During Rest

15. NRS in rest [1 year postoperatively]

    Numeric Rating Scale of Pain During Rest

16. NRS in rest [2 years postoperatively]

    Numeric Rating Scale of Pain During Rest

17. NRS during running [pre-operatively]

    Numeric Rating Scale of Pain During Running

18. NRS during running [3 months postoperatively]

    Numeric Rating Scale of Pain During Running

19. NRS during running [1 year postoperatively]

    Numeric Rating Scale of Pain During Running

20. NRS during running [2 years postoperatively]

    Numeric Rating Scale of Pain During Running

21. NRS during stair-climbing [pre-operatively]

    Numeric Rating Scale of Pain During Stair-Climbing

22. NRS during stair-climbing [3 months postoperatively]

    Numeric Rating Scale of Pain During Stair-Climbing

23. NRS during stair-climbing [1 year postoperatively]

    Numeric Rating Scale of Pain During Stair-Climbing

24. NRS during stair-climbing [2 years postoperatively]

    Numeric Rating Scale of Pain During Stair-Climbing

25. NRS during performing sports [pre-operatively]

    Numeric Rating Scale of Pain During Sports

26. NRS during performing sports [3 months post-operatively]

    Numeric Rating Scale of Pain During Sports

27. NRS during performing sports [1 year post-operatively]

    Numeric Rating Scale of Pain During Sports

28. NRS during performing sports [2 years post-operatively]

    Numeric Rating Scale of Pain During Sports

29. NRS during weight-bearing [pre-operatively]

    Numeric Rating Scale of Pain During Weightbearing

30. NRS during weight-bearing [3 months postoperatively]

    Numeric Rating Scale of Pain During Weightbearing

31. NRS during weight-bearing [1 year post-operativley]

    Numeric Rating Scale of Pain During Weightbearing

32. FAAM [pre-operatively]

    Foot and Ankle Ability Measure

33. FAAM [3 months postoperatively]

    Foot and Ankle Ability Measure

34. FAAM [1 year postoperatively]

    Foot and Ankle Ability Measure

35. FAAM [2 years postoperatively]

    Foot and Ankle Ability Measure

36. SF-12 [pre-operatively]

    Short-Form 12

37. SF-12 [3 months postoperatively]

    Short-Form 12

38. SF-12 [1 year postoperatively]

39. SF-12 [2 years postoperatively]

    Short-Form 12

40. Ankle Activity Scale (AAS) [pre-operatively]

41. Ankle Activity Scale (AAS) [3 months postoperatively]

42. Ankle Activity Scale (AAS) [1 year post-operatively]

43. Ankle Activity Scale (AAS) [2 year post-operatively]

44. Return to sports [post-operatively until 2 years of follow-up post-operatively]

45. Return to work [post-operatively until 2 years of follow-up post-operatively]

46. Radiological outcomes: CT-scan (depth, wide, length, joint space measurement) [pre-operatively]

47. Radiological outcomes: CT-scan (depth, wide, length, joint space measurement) [2 weeks postoperatively]

48. Radiological outcomes: CT-scan (depth, wide, length, joint space measurement) [1 year postoperatively]

49. Radiological outcomes: CT-scan (depth, wide, length, joint space measurement) [2 years postoperatively]

50. Radiological outcomes: MRI scan (T2 relaxation times) [Pre-operatively]

51. Radiological outcomes: MRI scan (T2 relaxation times) [1 year post-operatively]

52. Radiological outcomes: MRI scan (T2 relaxation times) [2 years post-operatively]

53. Cost-effectiviness [From per-operatively to post-operatively at 2 years (one period)]

    all relevant clinical costs will be scored through a patient diary

54. Cell-subset analysis [per-operatively]

    protein analyses will be performed by Sanquin

55. Demographic data [Pre-operatively]

    all kinds of demographic data will be assessed (age, gender, etc.)

56. Complications [From per-operatively to post-operatively at 2 years (one period)]

    all types of complications

57. Re-operations [From per-operatively to post-operatively at 2 years (one period)]

    re-operations will be assessed

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jari Dahmen, MD, BSc, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• ClinicalTrials.gov Identifier: NCT04475341
• Other Study ID Numbers: GK2019OUTBACK
• First Posted: Jul 17, 2020
• Last Update Posted: Jul 17, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Jul 17, 2020