Treatment of Refractory Patellar Tendinopathy with MSV *. Comparative study with P-PRP

INTERVENTION: Product Name: MSV ‐células progenitoras mesenquimales de médula ósea autóloga expandidas con procedimientos NCF Pharmaceutical Form: Living tissue equivalent INN or Proposed INN: MSV‐CMT Other descriptive name: EX VIVO CULTURED HUMAN MESENCHYMAL STEM CELLS Concentration unit: ml millilitre(s) Concentration type: equal Concentration number: 3300000‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use Product Name: P‐PRP Pharmaceutical Form: Injection INN or Proposed INN: P‐PRP Current Sponsor code: P‐PRP Other descriptive name: P‐PRP Concentration unit: µl microlitre(s) Concentration type: range Concentration number: 600000000‐800000000 CONDITION: Patients diagnosed with patellar tendinopathy with a minimum of 4 months evolution and have presented two acute episodes, refractory to standard treatments present a gap equal or greater than 3 mm at rest. ; MedDRA version: 20.0 Level: LLT Classification code 10034123 Term: Patellar tendinitis System Organ Class: 100000004859 Therapeutic area: Diseases [C] ‐ Musculoskeletal Diseases [C05] SECONDARY OUTCOME: Secondary end point(s): 1.‐ Pain and Functionality: The evolution of the classic visual analog scale (VAS) will be recorded, taking as reference the baseline value established before the treatment and by means of manual dynamometer (HHD) will measure the forces of extension of the knee. The somewhat functional evaluation will be performed using the VISA‐P score, specific to evaluate pain and functionality in patellar tendinopathy. It is a scale from 0 to 100. The value 100 would indicate absence of pain at rest, walking, going down or up stairs or during exercise (Hernández‐Sanchez 2012).; Usually patients with chronic patellar tendinopathy have values ??between 30 to 50, from 60 is allowed to start physical activity and with values ??above 70 is fit for competition, although in professional sports the demands are greater. The minimum significant difference has been set at 13 points. Criteria for the assessment of improvement applied in this trial (Hoksrud 2011):; ‐ Desired: = 60/100 (at 3 months) ; ‐ Very satisfactory: = 70/100 (at 6 months); ‐ Ideal: = 80/100 (at 12 months); ; 2.‐ Adverse Effects: Possible adverse events, related or not related with the procedure, that can occur throughout the test, will be recorded and tabulated.; ; 3.‐ Concomitant medication: The concomitant medication will be registered from the day of application of treatment, until the termination of the study. Timepoint(s) of evaluation of this end point: 12 Months PRIMARY OUTCOME: Main Objective: ‐Confirm the presence of regeneration of the patellar tendon gap after peritendinous and intratendinous infusion of MSV and the comparison with the P‐PRP group evaluated with ultrasound, MRI and UTC.; ; ‐To assess the clinical efficacy of MSV infusion by means of refractory patellar tendinopathy compared to the P‐PRP group by subjective patient outcomes, VAS and VISA‐P questionnaires and the strength of the extensor muscle group using dynamometry. Primary end point(s): The objective is to evaluate the response by:; ; 1. Ultrasound: The patellar tendon will be examined longitudinally and transversely using gray scale and color, exerting a minimal pressure with the probe. Images will be recorded in static and dynamic formats to build a consensus of the findings. The therapeutic action will be considered positive if there is evidence of improvement of the tendon ecotexture, reduction of the gap, reduction of neovascularization and, to a lesser extent, decrease in thickness, since this latter parameter is conditioned by the adaptive‐protective effect of the Increase in thickness; Ie both increase and decrease may represent a favorable aspect (Warden 2007).; It will be determined: 1. Location of the lesion (medial, central, lateral) and (anterior, central, posterior).; 2. Thickness of the tendon at 5 mm from the inferior pole of the kneecap.; 3. Ecotexture using scale 0‐3.; 4. GAP longitudinal, axial measures and area value.; 5. Vascularization degree I‐V; ; 2.‐ UTC: The tendon eco‐architecture will be evaluated by establishing 4 subtypes marked by ROIs in cross section: I, II, III, IV according to percentages.; The distance in millimeters from the lower pole of patella in anteroposterior and transverse section will also be measured according to percentages. "I" is considered the perfect value and corresponds to ecotexuture with linearity of the collagen fibers; 'IV' is the worst value that corresponds to absence of fibrillar organization. As a criterion of cure, we propose the evaluation of the 4 subtypes and evaluate the changes, calculating the increase in relative% of subtypes I and II and the decrease of subtypes III and IV.; ; 3.‐ MRI: UTE (Ultrashort Echo TE) sequences will be used in the sagittal plane and the ROI corresponding to the gap will be established in the medial‐lateral zone, external lateral zone and healthy tendon.; With T2 FAT SAT sequence (fat saturation) in the sagittal plane, the gap signal will be measured with different items: hyposignal, homogeneous, heterogeneous, isointense and normal.; The gap will be measured in mm proximally, medially and distally.; Hoffa fat edema and patellar bone edema will be evaluated.; The FFE (Fast FE) 3D sequence in the coronal plane will measure the gap in millimeters, the gap in transverse diameter and the existence of calcifications will be evaluated.; An intra‐articular study and quantification of the degree of arthrosis I‐IV of each compartment of the knee will also be carried out. Secondary Objective: To assess the viability and safety of the advanced therapy medicinal product MSV and P‐PRP when applied by percutaneous infusion into the patellar tendon, demonstrating that each of the procedures established in the protocol is feasible and registering the possible related adverse effects With both treatments and adverse events occurring during the clinical trial period, whether or not they are related to them. Timepoint(s) of evaluation of this end point: 12 meses INCLUSION CRITERIA: 1. Males with ages between 18 and 48 years. 2. Patellar tendon pain, located in the insertion zone, of more than 4 months duration that does not show significant improvement after conservative treatments such as rest, analgesia, physiotherapy and / or infiltration. 3. Echographic image confirming, in both static and dynamic states, the loss of the fibrillar structure of the proximal part of the patellar tendon, thickening of the patellar tendon and a hypoechogenic lesion compatible with a gap =3 mm. 4. Patellar tendon MRI scan T2 FAT SAT (fat saturation) showing a gap =3mm in longitudinal diameter at the proximal insertion. 5. Informed Consent in writing and signed by the patient. 6. The patient is able to understand the nature of the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.