Clinical trial NCT06960343: Long Term Clinical Outcome After Arthroscopic Rotator Cuff Repair Augmentation With Autologous Microfragmented Lipoaspirate Tissue
Official title: Long Term Clinical Outcome After Arthroscopic Rotator Cuff Repair Augmentation With Autologous Microfragmented Lipoaspirate Tissue: a Prospective Randomized Controlled Trialin Question Won by Our Research Group.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Arthroscopic Rotator Cuff Repair
Augmentation
Microfragmented Adipose Tissue
Lead sponsor: University of Milan
Sponsor class: OTHER
Collaborators: name: International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS)
name: ASST Gaetano Pini-CTO
First posted: 2025-05-07
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study is a prospective, randomized, double-blind, controlled clinical trial and represents the final follow-up of an our previous study with short follow-up (2 years). At least 5 years after surgery, all enrolled patients in the previous study will be call again and will be asked to complete the ASES, SST, and VAS questionnaire and they will undergo a clinical examination, including the CMS and measurement of isometric strength in shoulder forward flexion, abduction, and external rotation. All strength measures will be performed in triplicate with a dynamometer.

During the same assessment day, the patients would be evaluated with MRI of the operated shoulder in order to assess tendon integrity and calculate rerupture rate according to the classification proposed by Sugaya (types IV and V defined as retears). Atrophy of the supraspinatus muscle belly was evaluated according to Warner and fatty degeneration was classified according to Fuchs.

Brief summary: Specific Aims :

The aim of this prospective randomized controlled single-blind clinical trial was to evaluate the safety and efficacy of autologous microfragmented lipoaspirate tissue in arthroscopic rotator cuff repair.

The primary goal of this study was to test the following hypothesis: an intraoperative injection of autologous microfragmented adipose tissue processed with an enzyme-free technology could improve the clinical outcomes of single-row arthroscopic rotator cuff repair in terms of points in the Constant-Murley score (CMS) collected at least 5 years after surgery.

Background and Significance:

Rotator cuff surgery was initially proposed at the end of the 19th century and evolved then from open to arthroscopic techniques, rising quickly from a minor niche to a fully recognized subspecialty.

To improve clinical and functional results and reduce the retear rate, new fixation techniques and biological solutions to enhance tendon healing are being developed at a fast pace, as shown by the dramatic increase in the number of articles published per year.

Biological solutions to enhance rotator cuff healing include growth factors and platelet-rich plasma, as well as mesenchymal stem cells (MSCs) and their derivatives.

MSCs are believed to enhance tissue healing mainly through stimulation of local cells via paracrine mechanisms and anti-inflammatory and/or immunomodulatory activity, thus creating a suitable microenvironment for tissue repair.

Autologous microfragmented lipoaspirate tissue has been recently introduced in orthopaedics as an easily available source of adipose derived MSCs (ADSCs) to support and accelerate tissue regeneration. Lipoaspirates contain human ADSCs and produce growth factors, such as platelet-derived growth factor, fibroblast growth factor, transforming growth factor beta, and vascular endothelial growth factor, which play important regulatory roles in cellular functions, including adhesion, chemotaxis, proliferation, migration, matrix synthesis, differentiation, and angiogenesis.

Herewith, autologous microfragmented lipoaspirate tissue is expected to optimize the microenvironment for tendon regeneration. Among many approaches, devices relying on nonenzymatic methods and avoiding the use of additives and other additional manipulations (eg, centrifugation) allow one to harvest, process, and obtain autologous microfragmented lipoaspirate tissue directly in the operative theatre under sterile conditions. This permits immediate use in the same surgical intervention without delays owing to the difficulty of an ex vivo cell expansion and the complexity of the current good manufacturing practice requirements for preparing cells for therapeutic use.

Although several animal studies have been published showing promising results for the use of ADSCs in enhancing the healing of rotator cuff tears, minimal evidence describing augmentation of rotator cuff treatment with lipoaspirate.

Preliminary Studies/Progress Report:

This study is a prospective, randomized, double-blind, controlled clinical trial and represents the final follow-up of an our previous study with short follow-up (2 years). The previous study demonstrated that the intraoperative injection of autologous microfragmented adipose tissue is safe and effective in improving short-term clinical and functional results after single-row arthroscopic rotator cuff repair.

Nevertheless, no significant differences emerged between the groups in terms of rerupture rate, complication rate, number of adverse events, and mid-term clinical outcomes.

A previous in vitro study showed that autologous microfragmented adipose tissue significantly increases the proliferation rate of human tendon stem cells without altering their stemness and differentiation capability. Moreover, treated cells increase the expression of VEGF, which is crucial for the neovascularization of the tissue during the healing process.

Research Design and Method:

At least 5 years after surgery, all enrolled patients in the previous study will be call again and will be asked to complete the ASES, SST, and VAS questionnaire and they will undergo a clinical examination, including the CMS and measurement of isometric strength in shoulder forward flexion, abduction, and external rotation. All strength measures will be performed in triplicate with a dynamometer.

During the same assessment day, the patients would be evaluated with MRI of the operated shoulder in order to assess tendon integrity and calculate rerupture rate according to the classification proposed by Sugaya (types IV and V defined as retears). Atrophy of the supraspinatus muscle belly was evaluated according to Warner and fatty degeneration was classified according to Fuchs.


Eligibility criteria: Inclusion Criteria:

* Age \> 18 years
* Full-thickness supraspinatus and infraspinatus tendon tears (C1, C2, and C3 according to the SCOI classification)
* Indication for arthroscopic rotator cuff repair
* Informed consent to participate in the study
* Informed consent to participate for the duration of the study

Exclusion Criteria:

* Partial rotator cuff tendon tears (A1, A2, A3, B1, B2, and B3 according to the SCOI classification)
* Massive rotator cuff tear (C4 according to the SCOI classification)
* Subscapularis tendon tear (grade III, IV, or IV according to Lafosse classification)
* Associated anterior, posterior, or multidirectional shoulder instability
* Indication for repair of a SLAP lesion of the biceps anchor
* Grade III or IV muscle atrophy of the supraspinatus and infraspinatus tendons (according to Goutallier or Fuchs classification)
* Intra-articular hyaluronic acid or corticosteroid infiltration within 3 mo from the planned surgical procedure
* Medical comorbidities contraindicating arthroscopic shoulder surgery
* Local (shoulder, abdominal region, gluteal region) or systemic infection, osteomyelitis, or sepsis
* Diabetes mellitus, untreated thyroid disease, chronic kidney disease, rheumatoid arthritis
* Immunodeficiency
* Chronic disorders involving coagulation, platelet aggregation, or severe coagulopathy
* Severe cardiovascular disease
* Stroke or acute cardiovascular event within 6 mo from the planned surgical procedure
* Weight loss for any cause .30 kg in 12 mo or .10 kg in 12 mo without a cause
* Eating disorders or body dysmorphic disorder
* Varices, phlebitis, or scars next to the planned adipose tissue harvesting site
* Alcohol/drug addiction or psychiatric disease compromising compliance with postoperative protocols
* Pregnancy or breastfeeding women
* Informed consent not accepted

Primary outcomes:
measure: Comparison between the two groups of the incidence of retears at least 5 years after surgery
timeFrame: 5 years
Secondary outcomes:
measure: Comparison of the Constant-Murley score (CMS) between the two groups at least 5 years after surgery.
timeFrame: 5 years
measure: Comparison between the two groups of the difference in the Visual Analogue Scale (VAS) score at least 5 years after surgery.
timeFrame: 5 years
measure: Comparison between the two groups of abduction and external rotation strength at least 5 years after surgery.
timeFrame: 5 years
measure: Comparison of the ASES (American Shoulder and Elbow Surgeons score) and SST (Simple Shoulder Test) between the two groups at least 5 years after surgery.
timeFrame: 5 years
measure: Comparison between the two groups of the progression of supraspinatus fatty degeneration at least 5 years after surgery
timeFrame: 5 years
Other outcomes:
Locations:
city: Milan
country: Italy
facility: ASST Gaetano Pini-CTO
Study officials:
References:
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