Clinical trial NCT05865899: Impact of High Tibial Osteotomy in Preventing Degenerative Disease Progression in Medial Knee Osteoarthritis.
Official title: Impact of High Tibial Osteotomy in Preventing Disease Progression in Medial Knee Osteoarthritis: Quantifying the Effects on Cartilage and Subchondral Bone by Using a Combined Biomechanical and Medical Imaging Approach.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Knee Osteoarthritis
Cartilage Degeneration
Malalignment, Bone
Keywords: Knee
Osteoarthritis
Varus
Malalignment
Cartilage
Correction Accuracy
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
First posted: 2023-05-19
Enrollment: 50
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: High tibial osteotomy (HTO) surgical procedure can lead to clinically significant improvements in the cartilage and in subchondral bone quality, with a slow down of the osteoarthritis (OA) progression.

Aim of the project is to:

(i) clinically validate a 3D planned HTO surgical approach, through a quantitative grading of OA progression in a prospective randomized case-control clinical trial; (ii) correlate the internal knee loads with the changes assessed in cartilage and subchondral bone status to verify the hypothesis that HTO induced mechanical changes are associated with clinically significant OA improvements; (iii) relate imaging data with cartilage and subchondral bone mechanical properties, in order to classify OA progression in a more sensitive manner and allow a more precise diagnosis of the pathology stage.

Detailed description: High tibial osteotomy (HTO) is a well tracked procedure aimed to reduce the overload in the medial compartment of the varus knee with early and mid-stage osteoarthritits (OA).

Clear evidence still lacks regarding whether it has the ability to determine regenerative processes in the cartilage and subchondral bone. Furthermore, prospective randomised analysis regarding the effectiveness of HTO with respect to conservative treatment are needed.

The hypothesis is that an accurately planned HTO surgery result in measurable changes in the internal knee biomechanics, leading to clinically significant improvements in cartilage and subchondral bone quality, slowing down OA progression.

Accurate HTO could thus become the first choice in young/fit patients with medial knee OA, preserving their bone stock, slowing down OA progression and eventually reversing its trend, with a high impact on patients' quality of life and on public health system spending.

Aims of the study:

1. To quantify by quantitative imaging and subject-specific modeling the biomechanical changes induced in patients' joint by accurate HTO surgery, and the consequent changes of articular tissues composition and structure, related to OA progression.
2. To evaluate the surgical accuracy of a new 3D HTO planning system. Once association of biomechanical corrections with clinical outcome is established (Aim 1), such 3D HTO planning will help surgeons performing personalized HTO corrections.
3. To define an enhanced methodology for OA staging, by correlating quantitative medical imaging with mechanical properties of cartilage and subchondral bone.

Metodologies and statistical analyses:

Sample Size:The primary outcome of the study is the clinical assessment of cartilage/subchondral bone. In absence of standard subchondral bone scores, sample size has been determined on MRI T2 relaxometry, a reliable quantitative descriptor of cartilage in OA. Power analysis, based on cartilage T2 variations due to HTO (Independent t test, T2 expected difference 3.5 ms, standard deviation 4.5 ms, significance level 0.05, power 0.8, one tail), indicated 44 patients (22 per group). We target to enroll 50 patients to compensate for possible drop-outs.

Surgical technique: opening wedge HTO will be performed through a medial incision and stabilized with a plate and screws. Hardware will be removed within 10-12 months to avoid soft tissue irritation.

Imaging assessment: cartilage morphology and composition will be assessed via T1rho and T2 mapping from 3T MRI. Subchondral bone density and orientation will be computed from CBCT images. To quantify the biomechanical changes induced by HTO, subject-specific musculoskeletal models of the lower limbs will be created from MRI with nmsBuilder freeware, and used to calculate (with OpenSim software) knee loads during daily motor activities from marker trajectories and ground reaction forces measured in the gait analysis. A knee joint model enabling calculation of cartilage contact pressure will be implemented. Arthroscopic assessment of cartilage will follow the International Cartilage Repair Society (ICRS) score. Histological analysis of cartilage biopsies will be performed.

Eligibility criteria: Inclusion Criteria:

* medial knee osteoarthritis in varus knee malalignment (\> 4°)

Exclusion Criteria:

* Inability to sign informed consent
* joint infection
* inflammatory chronic disease
* previous major surgical procedure of the indexed knee (simple arthroscopy or meniscectomy would be not considered major procedure)
* BMI \> 30

Primary outcomes:
measure: Cartilage morphology and composition assessment via T1rho and T2 mapping from 3Tesla (3T) magnetic resonance imaging(MRI).
timeFrame: 3 years
measure: Subchondral bone morphological and structural analysis via Cone Bean Computed Tomography (CBCT) of the knee.
timeFrame: 3 years
measure: Clinical Score for Knee function 1
timeFrame: 3 years
measure: Clinical Score for Knee function 2
timeFrame: 3 years
measure: Clinical Score for Knee function 3
timeFrame: 3 years
Secondary outcomes:
measure: Gait analysis assessment
timeFrame: 3 years
measure: Scores for general health
timeFrame: 3 years
measure: Scores for pain
timeFrame: 3 years
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Stefano Zaffagnini
Study officials:
References: