Clinical trial NCT04889443: Spontaneous Healing of ARticular Cartilage (SHARC)
Official title: How do Cartilage Injuries Heal Naturally? An Observational Study of Spontaneously Healing Cartilage Defects
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cartilage Damage
Cartilage Injury
Keywords: Cartilage repair
Lead sponsor: Keele University
Sponsor class: OTHER
Collaborators: name: Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust
First posted: 2021-05-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients undergoing surgery that involves the harvest of cartilage tissue as part of the treatment

Brief summary: SHARC is an observational study of cartilage patients who are treated with surgery that involves obtaining a harvest biopsy. SHARC will study the natural healing process of the harvest biopsy site based on histological and biochemical analyses of repair tissue biopsies, synovial fluid biomarkers, medical imaging (MRI) and gait analysis.

Detailed description: Osteoarthritis (OA) is a very common disease of the joints, for which in the United Kingdom alone almost 9 million people have sought treatment. This painful disease affects the cartilage and bone inside the joint. Many factors are known to increase the risk of getting osteoarthritis, or the rate at which it gets worse. Very important among these factors is an injury or a defect of the cartilage. It was believed for hundreds of years that cartilage, once injured, does not heal.

Research from the past 10 years is now throwing doubt on this old certainty, as researchers who took regular scans of volunteers over time noted that sometimes these defects come and then go. A Japanese group of surgeons decided to look again after a year to see what had happened to these defects, and noted that about half of them had got better! Cartilage defects in human therefore can heal, but nobody knows how this works.

For many years, our Center has helped patients who have knee cartilage damage by using the patients' own cartilage cells to help repair areas of damaged cartilage. This cell therapy starts by taking a piece of cartilage (10 mm) from the patient's knee, and this created defect always heals after a year. Thus, our proposal is to use our cell therapy patients as a human experimental model of natural cartilage healing using a wide range of techniques including Magnetic Resonance Imaging (MRI), visual inspection of the joint itself during knee joint surgery, examining biopsies of repair tissue down the microscope and measuring various kinds of molecules researchers think are important. The information gathered from these tests will help bridge the gap in our understanding of the mechanisms involved in the cartilage tissue regeneration.

Eligibility criteria: Inclusion Criteria:

* Being able to provide signed and dated informed consent form.
* Scheduled for one of the following surgical treatments

  * Surgery that involves the harvest of cartilage tissue as part of the treatment, thus creating a fresh cartilage defect, which is then left to heal naturally. Examples of such surgery are autologous chondrocyte implantation (ACI) and mosaicplasty.
  * Autologous stromal cell implantation (ASCI), as part of the ASCOT randomised clinical trial.

Exclusion Criteria:

* Inadequate understanding of verbal explanations or written information given in English, or having special communication needs.
* Chronic severe renal insufficiency
* Anything that would preclude the individual's full compliance with or completion of the study.

Primary outcomes:
measure: Fraction of hyaline cartilage in harvest repair tissue
timeFrame: 1 year after tissue harvest
Secondary outcomes:
measure: Visual quality of the repair tissue in harvest repair tissue
timeFrame: 1 year after tissue harvest
measure: Quality of harvest repair tissue assessed from MRI images
timeFrame: 1 year after tissue harvest
measure: Mean signal intensity of harvest repair tissue on MRI
timeFrame: 1 year after tissue harvest
measure: Quality of harvest repair tissue assessed from a biopsy using the ICRS-II histology score
timeFrame: 1 year after tissue harvest
measure: Quality of harvest repair tissue assessed from a biopsy using the OsScore histology score
timeFrame: 1 year after tissue harvest
measure: Correlation of harvest repair tissue quality with baseline risk of osteoarthritis
timeFrame: 1 year after tissue harvest
measure: Correlation of harvest repair tissue quality with local mechanical load at the defect
timeFrame: 1 year after tissue harvest
measure: Match of biomarker level time course to a postulated pattern of cartilage repair, namely Inflammation-Repair-Remodelling.
timeFrame: 1 year after tissue harvest
measure: Correlation between levels of inflammatory biomarkers and inflammatory activity measured on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at baseline and 1 year.
timeFrame: 1 year after tissue harvest
measure: Correlation of level of levels of inflammatory activity determined in a repair tissue biopsy versus that measured on DCE-MRI.
timeFrame: 1 year after tissue harvest
Other outcomes:
Locations:
city: Oswestry
country: United Kingdom
facility: RJAH Orthopaedic Hospital NHS Foundation Trust
state: Shropshire
Study officials:
affiliation: Keele University
name: Jan Herman Kuiper, PhD
role: PRINCIPAL_INVESTIGATOR
References: