Clinical trial NCT06028763: Development of Biomedical Technology for the Treatment of Ankle Cartilage Using Injectable Biocomposite Hydrogel
Official title: Development of Biomedical Technology for the Treatment of Ankle Cartilage Using Injectable Biocomposite Hydrogel
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ankle Osteoarthritis
Keywords: Cartilage lesions
Osteoarthritis
Mesenchymal stem cells
Ankle arthroscopy
Lead sponsor: National Scientific Center of Traumatology and Orthopedics named after academician N.D. Batpenov
Sponsor class: OTHER_GOV
First posted: 2023-09-08
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 40 participants will divide into 2 groups main and control. Main group (n=20): implantation of heparin-conjugated fibrin hydrogel with autologous MSCs and growth factors (TGF-β1 and BMP-4) into the cartilage defect during arthroscopy.

Control group (n=20): arthroscopic debridement of the joint with microfracturing (traditional method of treatment).
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the effectiveness of heparin-conjugated gel for treating ankle joint cartilage lesions compared to the conventional microfracture method. It involves 40 participants aged 18 to 65 with localized cartilage defects (Outerbridge II-IV) in the ankle's talus bone.

Participants will be divided into two groups: the main group and the control group. The main group will undergo a two-stage process. Initially, adipose tissue will be collected via lipoaspiration from osteoarthritis patients. This tissue will be used to isolate mesenchymal stem cells (MSCs) and extract growth factors, resulting in a biocomposite hydrogel. In the second stage, arthroscopy will be performed to apply the hydrogel for cartilage treatment.

The control group will undergo standard microfracture surgery, a known cartilage repair method.

The study's main objective is to compare heparin-conjugated gel treatment to microfracture in terms of cartilage repair and patient outcomes. A 12-month follow-up will assess short-term and potential mid-term effects.

Data will be analyzed using Microsoft Excel and Statistica 13.0 for descriptive and comprehensive statistical analysis. Quantitative indicators will be assessed using appropriate tests (Mann-Whitney, Wilcoxon T, χ2) to determine significant differences between groups.

The study addresses key questions: Does heparin-conjugated gel offer better cartilage repair, functional improvement, and pain reduction than microfracture? Does the hydrogel approach better preserve joint integrity and slow degeneration? Are there complications with either method? This study combines cellular and surgical components to explore innovative cartilage lesion treatments. Comparing with microfracture and using a thorough follow-up, it aims to enhance cartilage repair techniques and patient outcomes.

Detailed description: Introduction:

This prospective clinical study aims to investigate the effectiveness of heparin-conjugated gel in treating patients with ankle joint cartilage lesions and to compare its outcomes with the traditional method of microfracture. The study aims to provide valuable insights into novel treatment options for cartilage repair.

Study Design and Participants:

The study plans to enroll 40 male and female patients aged 18 to 65 years with localized defects in the articular cartilage of the talus bone (Outerbridge II-IV) within the ankle joint. Participants will be evenly divided into two groups: the main group and the control group, each comprising 20 participants.

Interventions:

Main Group:

In the main group, participants will undergo a comprehensive two-stage treatment approach:

Stage 1 - Biocomposite Hydrogel Preparation:

Subcutaneous adipose tissue will be collected from patients with signs of ankle joint osteoarthritis through lipoaspiration. The extracted tissue will be transferred to the Kazakh National Center of Biotechnology (Astana, Kazakhstan) for the isolation and cultivation of mesenchymal stromal cells (MSCs). A biocomposite hydrogel, containing MSCs and growth factors (TGF-β1 and BMP-4), will be obtained.

Stage 2 - Arthroscopic Cartilage Therapy:

Participants will undergo arthroscopy of the ankle joint. A heparin-conjugated fibrin hydrogel enriched with MSCs and growth factors will be applied to treat cartilage pathology.

Control Group:

The control group will receive the standard microfracture procedure for ankle cartilage lesion under arthroscopic control.

Follow-Up and Safety Assessment:

A 12-month follow-up period will be implemented to assess short-term and potential mid-term effects. Safety assessment of the heparin-conjugated hydrogel will be based on clinical wound healing assessment, local joint changes, and laboratory data (ESR, white blood cell count, C-reactive protein) 5-7 days post-surgery.

Clinical Evaluation:

The therapeutic efficacy of the heparin-conjugated hydrogel will be evaluated using clinical scales and questionnaires, including the American Orthopedic Foot and Ankle Score (AOFAS) and Visual Analogue Scale (VAS) for joint function and quality of life assessment.

Imaging and Rehabilitation:

Prior to surgery, patients will undergo magnetic resonance imaging (MRI) for defect confirmation and dimension assessment using The Magnetic Resonance Observation of Cartage Repair Tissue (MOCART) scale. Postoperative rehabilitation will be tailored individually based on defect characteristics and patient progress. Axial load on the operated limb will be limited for 6 weeks. Gradual weight-bearing will occur from the 6th to the 12th week.

Postoperative Monitoring:

Cartilage condition and joint health will be monitored postoperatively. Hydrogel survival and cartilage defect closure will be observed using MRI at 6 and 12 months.

Data Analysis:

Statistical analysis will use Microsoft Excel and Statistica 13.0. Descriptive statistics methods will calculate means (M) for parametric indicators, medians (Me) and interquartile ranges (Q25-Q75) for non-parametric indicators, and standard deviations (SD). The Mann-Whitney and Wilcoxon T criteria will assess quantitative differences. The χ2 criterion will assess qualitative parameters. Significance will be considered at p\<0.05.

Conclusion:

This study's rigorous design aims to contribute to understanding the effectiveness of heparin-conjugated gel for ankle cartilage repair, offering potential improvements over traditional microfracture. Insights gained from this study may lead to enhanced treatment options for patients with cartilage lesions in the ankle joint.

Eligibility criteria: Inclusion Criteria:

* patients with a local defect of articular cartilage of the talus bone (Outerbridge II-IV) of the ankle joint;
* an area of no more than 3 cm2 for a single defect or 20 cm2 for multiple defects of the cartilaginous tissue of the talus bone of the ankle joint;
* voluntary consent to participate in the study.

Exclusion Criteria:

* age 18\< and \>65
* progressive osteoarthritis of the ankle joint in the late stages;
* synovitis of the ankle joint;
* instability of the ankle joint;
* BMI\<29.9;
* presence of non-sanitized foci of chronic infection;
* severe mental illnesses (schizophrenia, psycho-organic syndrome);
* hormonal osteopathy;
* hemiparesis on the side of the proposed operation;
* neoplasms of other localizations with or without metastases;
* absence (refusal) of voluntary consent to participate in the study.

Primary outcomes:
measure: The American Orthopedic Foot and Ankle Score
timeFrame: 6; 12 months after surgery
measure: Visual Analogue Scale
timeFrame: 6; 12 months after surgery
Secondary outcomes:
measure: Magnetic resonance imaging of ankle
timeFrame: 6; 12 months after surgery
measure: Complete Blood Count
timeFrame: 5 days after surgery
measure: C-reactive protein
timeFrame: 5 days after surgery
Other outcomes:
Locations:
city: Astana
country: Kazakhstan
facility: Center of National Scientific center Of Traumatology and Orthopedics named after academician N.D. Batpenov
Study officials:
References: