Clinical trial NCT06505135: Stem Cell Treatment for Regeneration of the Rotator Cuff (Lipo-Cuff Study)
Official title: Stem Cell Treatment for Regeneration of the Rotator Cuff (Lipo-Cuff Study)
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Rotator Cuff Tears
Rotator Cuff Injuries
Rotator Cuff Tear Arthropathy
Keywords: Stem cells
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
First posted: 2024-07-17
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is designed as a prospective, randomized interventional trial to evaluate the effectoutcome of the treatment of rotator cuff tear with combined standard surgical attachment (standard care) of the supraspinatus tendon and supplementary injection of micro-fragmented tissue into the supraspinatus muscle (cell treatment group) compared to standard care only.
Primary purpose: TREATMENT

Brief summary: Treatment of rotator cuff tears with micro-fragmented adipose tissue is a minimal-invasive procedure with the potential to shorten and ease recovery, accelerate return to daily activity and work of thus with a potential capacity to improve the functional result compared to conventional surgery alone. The study will provide evidence whether the addition of micro-fragmented adipose tissue therapy can augment conventional rotator cuff tear treatment. The study will also reveal whether this treatment can be feasible for standard care of patients with rotator cuff tear as it will be simple to standardize. Moreover, besides providing a novel treatment for patients with rotator cuff tears, the project will based on data from muscle biopsies and scanning modalities, generate new knowledge, preparing for precision regenerative medicine in shoulder disease.

Detailed description: Damage to the tendons that stabilize the shoulder, particularly the supraspinatus tendon tear, has been recognized as the key lesion in rotator cuff tears. However, the lack of full functional recovery after surgical tendon reconstruction suggests that additional changes in the tissue are obstacles to rehabilitation. Recent studies demonstrate pathological changes in the supraspinatus muscle in animal models as a consequence of tendon tear. The muscle pathology includes muscle fibre atrophy, intracellular lipid accumulation, mitochondrial dysfunction, fibril disorganization, and reduced regenerative capacity. Moreover, fibrosis, accumulation of adipocytes, and inflammation develop in these muscles. Muscle strength is decreased by 30% several months after rotator cuff tear repair. Thus, the muscle becomes weaker and stiffer despite repair, suggesting that treatment of rotator cuff tear should include managing cuff muscle dysfunction.

Adipose derived cell therapy Muscle regeneration occurs in a specific environment to which several cell types contribute. The resident stem cell in skeletal muscle is the satellite cell. When skeletal muscle is damaged, the satellite cells are activated and start to proliferate to muscle repairing myoblast. Additional cell types support the regeneration by modulating the myoblast response, inflammation and vascularization. Skeletal muscle harbours a mesenchymal cell, the Fibro-Adipogenic Progenitor (FAP) cell. We have shown that FAPs respond to muscle damage, and is part of the muscle stem cell niche with supportive functions in muscle regeneration. This makes the use of FAPs or mesenchymal cells with a similar function derived from fat an interesting approach for muscle repair.

Implantation of various preparations of cell material that contain Mesenchymal Stromal Cells (MSC) have been used as therapy in a wide range of disorders including lesions in cardiac muscle. The most common sources of cells have been the bone marrow and adipose tissue, and the preparations have ranged from crude isolates of mononuclear cells, e.g. total stromal cells to more homogenous cultured cell isolates, that mainly contain MSC. Although these mesenchymal cells are able to differentiate into tissues such as bone and fat18, their major implication in tissue repair appears to be a capacity to support the regenerative milieu. Their known capacities include stimulation of tissue-specific cells like the myogenic cells, induction of vessel growth, and regulation of inflammation and apoptosis. Cells extracted from adipose tissue cells have shown a regenerative effect without major adverse effects when used as therapy in a range of tissue. Compared to skeletal muscle it is easier and less traumatic to obtain regenerative cells in a sufficient quantum from adipose tissue.

Production of cell preparations exclusively consisting of MSC requires isolation procedures and culturing for weeks, all of which has to be performed in certified laboratories. In case of homolog transplantation, the patient will have to have tissue harvested weeks before the operation. However, cell preparations enriched with MSC can be manufactured with simple, physical treatment of aspirated adipose tissue in a closed system. This can take place in the operation theatre within an hour. This means, that the preparation can be performed the same day as the implantation shall take place, in connection with the main operation.

The adipose tissue will be processed with cutting, grinding, and filtering - not to be considered as substantial manipulation. Likewise, the expected functions of the implanted, active cells in muscle are also found in adipose tissue, which is why the material probably not should be considered as engineered.

The material is derived from adipose tissue and will be used in skeletal muscle, and the use can in this respect be considered non-homologous. However, as the expected major functions in skeletal muscle are the same as in adipose tissue, the function may be accepted as homologous.

Therefore this trial treats patients in a one-day procedure. The adipose tissue will be harvested and processed as an initial procedure during surgery. At the end of the tendon suture procedure, the MSC enriched fragmented tissue will be injected into the supraspinatus muscle.

Eligibility criteria: Inclusion Criteria

* Clinical signs and symptoms compatible with a traumatic RCT
* MR verified supraspinatus tear
* Reparable lesion with tendon retraction \< 2 cm.
* Fatty infiltration level 0-2 (out of 5) according to Fuchs et al. and based on Goutalliers classification
* No history of inflammatory disease
* ASA score \< 3 (patients in good health)
* Signed consent to the study (including use of relevant data from the patient's electronic health records)

Exclusion Criteria

* No MRI of the shoulder
* Former surgery in the affected shoulder
* Signs of infection
* Immunosuppression (due to clinical condition or medical therapy)
* History of inflammatory disease
* Malignancy within 5 years
* Previous radiotherapy to the shoulder
* BMI under 18
* BMI above 35
* Coagulopathy
* Non-Danish speaking patients

Primary outcomes:
measure: Patient reported outcome of Oxford shoulder score
timeFrame: From inclusion and until 12 months after operation
Secondary outcomes:
measure: Clinical healing of the shoulder
timeFrame: 12 months post surgery
measure: Radiological healing
timeFrame: baseline, 6 and 12 months post-surgery
measure: Functioning of the supraspinatus muscle with improved muscle strain
timeFrame: baseline, 3, 6 and 12 months post-surgery
measure: Oxford shoulder score
timeFrame: baseline, 3, 6 and 12 months post-surgery
measure: Quality of life (EQ5D)
timeFrame: baseline, 3, 6 and 12 months post-surgery
Other outcomes:
Locations:
city: Sønderborg
country: Denmark
facility: Orthopaedic Research Unit, Department of Orthopaedics, Hospital Sønderjylland, Region of Southern Denmark.
state: Danmark
Study officials:
affiliation: University of Hospital of Southern Denmark - Aabenraa
name: Lars H. Frick, Prof.
role: PRINCIPAL_INVESTIGATOR
References: