Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT02308358 |
| Other study ID # |
1210204 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 2014 |
| Est. completion date |
July 2015 |
Study information
| Verified date |
August 2023 |
| Source |
University of Missouri-Columbia |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The purpose of this study is to evaluate the functional and clinical outcomes of patients
receiving femoral condyle osteochondral allografts, to evaluate potential predisposing
factors to failure of such grafts, and to compare the overall outcomes of the grafts to the
current standard of care for smaller lesions, microfracture. Our hypothesis is that patients
treated with these allografts will demonstrate significant functional improvement as measured
by validated outcome scoring measures and their function will be at least equal to that of
microfracture outcomes.
Description:
Localized articular cartilage defects are a common and challenging problem, particularly in
young patients. These defects cause significant disability and, as participation in sports
activity grows, are increasing in overall number annually. A recent systematic review
evaluating the overall full-thickness focal chondral defects in athletes revealed the
prevalence to be 36%, with 22% of the athletes being symptomatic. As the prevalence of these
injuries increases, they pose increasingly significant challenges to the clinicians who treat
them.
Normal joint cartilage is a firm, elastic tissue that covers the ends of bones to protect
them and allow smooth, pain-free movement over each other. Joint cartilage is described,
macroscopically and microscopically, as articular or "hyaline" cartilage. Hyaline cartilage
is often described as a "glass-like" structural tissue because of its shiny appearance and
translucency. The tissue structure is a hydrated matrix consisting of proteoglycans and at
least 90% (dry weight) Type II collagen fibers. The collagen fibers contribute to the overall
tensile strength and the proteoglycans provide the stiffness and tissue resiliency. Cartilage
cells, or chondrocytes, produce dense matrix, which effectively incarcerate the cells
themselves. In the event of injury, the motility of these cells is restricted due to their
inclusion deep inside the matrix, and the avascularity of the cartilage itself. This lack of
a vascular network prevents the infiltration of inflammatory cells and bioactive molecules
following damage. Thus, once damaged, adult articular cartilage will not effectively heal or
regenerate.
Treatment techniques of osteochondral lesions are relatively new and frequently changing and
evolving. The treatment algorithms for these injuries are complex and often involve multiple
procedures, including non-surgical interventions with pharmacological agents such as oral
non-steroidal anti-inflammatory drugs (NSAIDs), injectable corticosteroids, and activity
modification including rehabilitation and support braces that may provide incomplete or
temporary relief. Lesion characteristics such as grade and thickness may also impact
treatment options and recovery. Arthroscopic debridement and lavage is effective as a
first-line surgical approach for subjects with low physical demands. This procedure
eliminates debris and decreases inflammation in the joints, but the symptomatic relief is
usually transient and the lesion is not repaired. Treatments providing long-term results may
be achieved through a variety of surgical options.
There are many surgical treatments options currently available and each have limitations.
Marrow stimulation techniques include microfracture, drilling, and abrasion arthroplasty. The
Microfracture technique has been described to address lesions up to 1 cm2 while other authors
cite more specific applications depending on lesion size, patient age and physical demands.
While microfracture is considered a reparative treatment, the procedure can produce less than
optimal results because of the inferior nature of fibrocartilaginous tissue formed. Unlike
the Type II collagen normally found in articular cartilage, fibrocartilage consists
predominately of Type I collagen. Because it lacks the long-term wear characteristics of
normal hyaline cartilage, fibrocartilage can degrade with time.
ACI is a two-staged procedure developed to treat cartilage defects in the knee. For ACI, a
primary arthroscopic procedure is performed to assess the defect and a small amount (200mg to
400 mg) of healthy, autologous cartilage is harvested. The tissue is then expanded using a
cell-culture process over a period of several weeks. The expanded cells are then implanted
into the area of the defect during a second surgical procedure. Studies have demonstrated
through histology and quantitative measurements that ACI produces a "hyaline-like cartilage"
with a collagen type II content of between 35 percent and 55 percent. Literature indicates
that hyaline cartilage may have greater biomechanical strength and integrity than the
fibrocartilaginous tissue generated in lesions treated with microfracture. There are several
disadvantages using ACI, however, such as the need for two surgeries. It has increased
surgical time due to and it is associated with substantial cost to account for ex vivo cell
expansion. Potential postoperative complications related to the periosteal patch include cell
leakage, hypertrophy and/or delamination, and unequal chondrocyte distribution within the
lesion.
Osteochondral grafting, the direct transplantation of an osteochondral autograft or
allograft, is the only technique available on the market that transplants intact hyaline
cartilage. Fresh osteochondral allografts use active chondrocytes while avoiding donor site
morbidity. The grafts are avascular and aneural, meaning they are immunopriveleged and
suitable for transplantation. Autograft plugs are typically used to treat small defects (up
to 2.5 cm in diameter) due to donor site size limitation. Osteochondral allografts can be
harvested up to 35 mm in diameter or an entire compartment can be resurfaced using a shell
technique.Clinical outcome of osteochondral autografts has been documented in various studies
as good to excellent, particularly in subjects with isolated femoral lesions. A major benefit
of osteochondral allografts is their ability to provide the surgeon with the capability to
treat much larger defects. A major drawback of many of the aforementioned treatment options
(microfracture, ACI, osteochondral autograft) is their inability to treat such large lesions.
Additionally, fresh OCA longevity after implantation has been documented to be as long as 25
years, indicating that this procedure can provide long term relief to patients.
The purpose of this study is to evaluate the functional and clinical outcomes of patients
receiving femoral condyle osteochondral allografts, to evaluate potential predisposing
factors to failure of such grafts, and to compare the overall outcomes of the grafts to the
current standard of care for smaller lesions, microfracture. Our hypothesis is that patients
treated with these allografts will demonstrate significant functional improvement as measured
by validated outcome scoring measures and their function will be at least equal to that of
microfracture outcomes.
