Clinical trial NCT03905824: The Effectiveness of Adding Allogenic Stem Cells After Traditional Treatment of Osteochondral Lesions of the Talus
Official title: Randomized, Multicentric, Prospective, Double-blind Study: Effectiveness of Adding Allogenic Stem Cells to a Platelet-poor Plasma Scaffold After Arthroscopic Debridement and Microfractures in Patients With Osteochondral Lesions of the Talus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Osteochondral Fracture of Talus
Lead sponsor: University of Chile
Sponsor class: OTHER
First posted: 2019-04-05
Enrollment: 70
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Randomized, multicentric, prospective, double-blind study: effectiveness of adding allogenic stem cells to a platelet-poor plasma scaffold after arthroscopic debridement and microfractures in patients with osteochondral lesions of the talus Osteochondral lesions of the talus (LOC), affects the ankle cartilage, which it seems to have less repair capacity than that of other joints such as the knee of the hip. The LOC can be an important source of pain and affects comparatively younger, working age and athletically active patients.

Although there are several therapeutic strategies, debridement and microfractures performed arthroscopically are the most frequent procedures. After this surgery, it is expected that fibrocartilage will form that covers the osteochondral lesion. Though good results have been reported, this fibrocartilage presents histological characteristics of lower quality to those of the native articular cartilage.

Based on previous studies in different joints, it is hypothesized that the augmentation treatment of osteochondral lesions of the talus with mesenchymal allogeneic stromal cells derived from the umbilical cord produces better clinical and imaging results than standard treatment with debridement and microfractures only.

Therefore, the present study seeks to compare the effectiveness of traditional debridement and microfracture treatment versus adding a platelet-poor plasma (PPP) scaffold embedded in allogeneic mesenchymal stromal cells derived from the umbilical cord in patients with osteochondral lesions of the talus.

Detailed description: As with other major joints of the lower limb that carry weight (hip, knee), the osteochondral lesion (LOC) of the talus, can be a major source of pain and disability for the affected patient. The LOC of the talus can appear after one (or repeated) traumatic injury, compromises the bone and adjacent cartilage, being able to cause blisters in the cartilage layers, lesions similar to a cyst within the bone under the cartilage, or fracture of the cartilage and the bony layers.

The ankle joint supports multiple loads of the corporal weight in the daily activities, the reason why the properties of the cartilage in the ankle are different from those that appear in the hip and the knee. In the absence of an injury, the cartilage of the ankle has better resistance and tension properties to face the increase of forces than the hip or knee throughout life.

However, once an injury appears, the cartilage of the ankle appears to have less repair capacity compared to the hip or knee. Since the most common cause of LOC of the talus is post-traumatic, the average age of these patients is comparatively lower than that of patients affected by injuries to other joints.

Osteochondral injuries have an incidence of 27 per 10,0000 inhabitants in the USA. They are injuries that usually affect the working population and active sportsperson, producing pain, functional limitation and that probably contribute towards the evolution of an accelerated joint degeneration. Currently, there are multiple treatment modalities used by ankle and foot surgeons. These include debridement and microfractures of the subchondral plaque, utilization of totipotential cells, osteochondral autograft/allograft, tibiotalar arthrodesis, and partial/total ankle arthroplasty. However, no treatment offers a clear superiority over the others.

Debridement and microfractures performed arthroscopically is the most frequently used procedure and involves; the removal of degenerated cartilage and subchondral bone; obtaining firm lesional edges that prevent the spread of the lesion; and finally the stimulation of the bone marrow talar by performing microfractures of the subchondral plate. This with the hope that fibrocartilage will form that covers the osteochondral lesion. Although this fibrocartilage has histological characteristics different from those of native articular cartilage, good results have been reported in 82% of the cases when combining good quality studies in this regard.

The standard technique is not able to generate a replacement articular cartilage strong enough to support the joint loads to which the ankle is exposed. Therefore, clinical trials seek to increase the traditional treatment of debridement and microfractures with the intra-articular use of totipotent cells at the end of the procedure. Although the results of these series are promising and comparable at least to those of traditional treatment, the absence of comparative studies between them complicates the choice of treatment for both the patient and the surgeon. For this reason, the investigators have designed a prospective, comparative, double-blind study that will allow elucidating which of these interventions is the best alternative for our patients.

General Objective:

To compare the effectiveness of traditional debridement and microfracture treatment versus adding a platelet-poor plasma (PPP) scaffold embedded in allogenic stromal mesenchymal cells derived from the umbilical cord in patients with osteochondral lesions of the talus.

Specific Objectives:

* To compare functional and radiological results before versus post-surgery within each group studied (control and experimental)
* To compare functional results after surgery of the groups in traditional treatment versus traditional treatment plus mesenchymal stromal cells (MSC).
* To compare the quality of repair of the tissues of the groups in traditional treatment versus traditional treatment plus mesenchymal stromal cells (MSC).

Work hypothesis:

The augmentation treatment of the osteochondral lesions of the talus with mesenchymal cells produces better clinical and imaging results than standard treatment with only debridement and microfractures.

Eligibility criteria: Inclusion Criteria:

* Patients with a symptomatic osteochondral lesion of the Talus.
* Magnetic resonance of the ankle showing osteochondral injury of a single talus, with perilesional oedema

Exclusion Criteria:

* Recurrent osteochondral lesions of the talus
* Multiple osteochondral lesions
* Severe ankle instability, requiring open repair
* History of a previous foot or ankle surgery of the ipsilateral foot
* Rheumatoid arthritis
* Inability to return to the surgery site to practice long-term follow-up evaluations or lack of readiness to complete the indicated evaluation forms.
* Patients with a qualitative or quantitative commitment that prevents consent or assent their participation in the study.

Primary outcomes:
measure: Change on tissue reparation quality
timeFrame: Baseline and 1 year follow up
measure: Change over time of general health status
timeFrame: Baseline, 1 year and 2 years follow up
measure: Change over time of functional limitations of foot and ankle.
timeFrame: Baseline, 1 year and 2 years follow up
measure: Change over time of functionality of musculoskeletal ankle and foot pathology
timeFrame: Baseline, 1 year and 2 years follow up
measure: Change on declared pain
timeFrame: Baseline, 1 year and 2 years follow up
Secondary outcomes:
measure: Surgical time
timeFrame: During surgery
measure: Complication rate
timeFrame: Two years follow up from baseline (surgery)
measure: Cost-effective comparative analysis
timeFrame: Two years follow up from baseline (surgery)
Other outcomes:
Locations:
city: Santiago
country: Chile
facility: Universidad de Chile Clinical Hospital
state: Independencia
Study officials:
affiliation: Universidad de Chile Clinical Hospital
name: Manuel Pellegrini, MD
role: PRINCIPAL_INVESTIGATOR
References: