Evaluation of the Efficacy of the Use MD Tissue Collagen Medical Device in the Infiltrative Treatment of Greater Trochanter Pain Syndrome (GTPS)

Study Overview
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Brief Summary
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Greater Trochanteric Pain Syndrome, also known as GTPS (Greater Trochanteric Pain Syndrome) is a complex clinical condition characterized by chronic and recurrent pain in the lateral region of the hip, near the greater trochanter of the femur. Biomechanical and anatomic-histologic interactions of the structures of the peri trochanteric space, in which, given the close anatomic-functional relationships, the origin can be traced to three different pathologic entities that may influence each other and fuel the progressive exacerbation of symptomatology. These are: external snap hip, trochanteric bursitis, and tendinopathies of the tendons of the gluteus mediums and gluteus minimums muscles. Recent studies regarding GTPS have shown that in most cases this condition is due to degenerative tendinopathy of the tendons of the gluteus minimums and gluteus mediums muscles. Tendinopathy is defined as a pathological condition associated with histological changes that may result in a change in the organization of collagen fibrils, relative increase in the percentage of proteoglycans, glycosaminoglycans, and no collagenous components of the ECM accompanied by neo-vascularization and inflammatory state. Tendinopathies thus result in painful symptomatology that very often also results in biomechanical functional deficit. Clinically, GTPS presents as pain that is often debilitating and exacerbated by activities such as walking, climbing stairs, and lying on the affected side at night, associated with a progressive loss of stenia in hip abduction movements. On objective examination, a point of tenderness (trigger point) is noted at the level of the region of the greater trochanter, which may radiate to the lumbar area and along the lateral aspect of the thigh to the ipsilateral knee and a difficulty on strength versus resistance tests in hip abduction movements. Although it is a very common syndrome, the treatment of painful grand trochanter syndrome, as well as that of tendinopathies in general, is still a major hurdle because the specific cellular pathogenetic and biomechanical etiopathogenetic mechanisms are still partly unknown and many treatments are empirical. Traditionally, the treatment of GTPS is initially conservative and includes rest, ice, NSAIDs and physiotherapy with stretching exercises of the fascia late. The use of corticosteroids, with systemic or local infiltrative intake, for the treatment of tendinopathies is highly controversial and, in any case, does not seem to have long-term efficacy. MD-Tissue Collagen Medical Device is an injectable medical device based on porcine collagen type I; the collagen content is 100µg/2mL. Porcine collagen is like human collagen and highly compatible; it has very low risks of inducing adverse effects and is therefore used in several clinical settings.

Detailed Description
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This is a pilot monocentric Clinical Investigation based on a One sample design. In the ex vivo study, MD-Tissue Collagen Medical Device was used as a substrate for cell cultures of human gluteal tenocytes on culture plates. The results suggest how MD-Tissue can induce an anabolic phenotype in tenocytes by stimulating their proliferation and migration; it would also be able to promote the synthesis, maturation, and secretion of COL-I, thereby promoting tendon homeostasis and repair. Specifically, the modification of gene expression and proteins involved in collagen turnover pathways were analyzed by real-time PCR, Slot blot and SDS-zymography. Data from the study showed that tenocytes cultured with MD-Tissue compared with controls exhibited increased secretion and migration of COL-1 increased mRNA levels of the matrix metalloprotease inhibitor proteins MMP-1 and TIMP-1. The tenocytes used for the cell cultures were gluteal tenocytes, derived from human gluteal tendon fragments (obtained from subjects without any tendon pathology who had undergone total hip replacement surgery); therefore, it is reasonable to think that the porcine type I collagen-based compound may be a viable treatment in GTPS. The results of the preclinical study suggest how MD-Tissue Collagen Medical Device can induce an anabolic phenotype in tenocytes by stimulating tenocyte proliferation and COL-I synthesis, maturation, and secretion, thereby promoting tendon repair. As these effects have been evaluated ex vivo on tenocytes of gluteal muscle tendons, the purpose of this study is to evaluate its efficacy in local infiltrative treatment, in the pertechnetic region, of GTPS, in terms of resolution of pain symptoms and recovery of stenia in abduction. Variables will be assessed at 6 different times; at baseline (day 0), after week 1, weeks 2, weeks 6, weeks 10 and after weeks 24.

Official Title
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Evaluation of the Efficacy of the Use of a Type I Collagen-based MD Tissue Collagen Medical Device in the Infiltrative Treatment of Greater Trochanter Pain Syndrome (GTPS) MEDANTRO PILOT STUDY

Conditions
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Greater Trochanteric Pain Syndrome, GTPS - Greater Trochanteric Pain Syndrome, Tendon Disorder, Pertrochanteric Fracture, Gluteal Tendinitis, Gluteal Muscles

Intervention / Treatment
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* Device: MD Tissue Collagen Medical Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects aged 18 to 70 years; subjects with lateral palpatory pain that has appeared for at least 1 month; subjects with hip pain symptomatology assessed by Numerical rating scale (NRS) ≥ to 5; Subjects able to cooperate for the assessments in the Survey plan; subjects able to understand and sign informed consent. Exclusion Criteria: subjects with true coxalgia (with positive FADDIR); subjects with ESHS (external snap hip syndrome); subjects already undergoing candidate hip replacement surgery; subjects with radiologic and clinical evidence of small and/or middle gluteal tendon detachment with indication for surgical repair; subjects with evidence of radiographically documented tendon calcifications; subjects with a degree of coxarthrosis of the hip that is a candidate for treatment according to the classification of Tonnis>1 subjects who have taken fluoroquinolones within 30 days prior to enrollment subjects who have undergone treatment with hyaluronic acid or corticosteroids in the hip candidate for infiltrative treatment within 4 weeks before enrollment; subjects with local infections of the treatment candidate hip or systemic infections, osteomyelitis, or sepsis; subjects on chronic treatment with corticosteroids or immunosuppressants; subjects who are drug addicts, alcoholics, have psychiatric disorders, or have clinical conditions that may compromise the correct interpretation of PROMs or follow-up; subjects with coagulopathies, platelet aggregation disorders, or on treatment with oral anticoagulants or antiplatelets that cannot be discontinued during the study period; Pregnant and lactating subjects (female subjects of childbearing age should be tested for pregnancy before enrollment); subjects with allergy to porcine collagen.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: One sample study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MD-Tissue Medical Device<br> | Device: MD Tissue Collagen Medical Device<br>* The Experimental Group will be treated with 2-mL volume ultrasound-guided infiltration of: MD-Tissue (GUNA, Milan-Italy). Composition for 2 ml: collagen 100 micrograms Subjects will be treated with No.1 infiltration per week for 3 consecutive weeks. The infiltrations will be performed in an echoguided mode. MD-Tissue Collagen Medical Device will be infiltrated into the trochanteric bursa and at the level of the tendons of the gluteus minimus and gluteus medius, particularly at the level of the most degenerated insertional areas.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the NRS (Numerical rafing scale score) at time week 10 to determinated the absence or tolerance pain. | The primary end point will be assessed at week 10 and will include: - Evaluation of the NRS score at time week 10 compared to day 0. The numerical scale goes from zero to 10. Zero is the absence of pain, 10 is intolerable pain, 3 is the limit of tolerance allowed by the OMS. There is also a verbal scale that distinguishes between absent, mild, moderate, severe, very severe, intolerable pain. It can be considered clinically significant if at least 50% of treated subjects present a reduction of at least 3 points on the NRS scale. | weeks 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the NRS score at time week 6 and week 24 compared to time T0, to determinated the absence or tolerance pain. | Evaluation of the NRS (Numerical rafing scale score) at time week 6 and week 24 compared to time day 0, to determinated the absence or tolerance pain. The numerical scale goes from zero to 10. Zero is the absence of pain, 10 is intolerable pain, 3 is the limit of tolerance allowed by the OMS. There is also a verbal scale that distinguishes between absent, mild, moderate, severe, very severe, intolerable pain. It can be considered clinically significant if at least 50% of treated subjects present a reduction of at least 3 points on the NRS scale. | weeks 6 and weeks 24 | 
| Assessment of mHHS (Modified Harris Hip Score) score to evaluate worst functional outcome and maximum pain to 100 points (best functional outcome and least pain). | Assessment of mHHS score (Modified Harris Hip Score) at time 6 weeks, 10 weeks and weeks 24 compared with time day 0. The modified Harris hip score was scored from 0 (worst functional outcome and maximum pain) to 100 points (best functional outcome and least pain). | weeks 6, weeks 10 and weeks 24 compared to time day0. | 
| Clinical evaluation of force in abduction | Clinical evaluation of stenia in abduction at time week 6, week 10 and time week 24 compared with time day 0, force will be assessed, with subject standing on the healthy limb, by measurements of abduction force of the GTPS-affected hip using a dynamometer. | weeks 6, weeks 10, weeks 24 compared to day 0 | 
| Evidence of resolution or decrease in inflammatory and degenerative signs of the eritrochanteric region of the GTPS-affected hip on MRI investigation | Evidence of resolution or decrease in inflammatory and degenerative signs of the peritrochanteric region of the GTPS-affected hip on MRI investigation at week 24 compared to day 0. | weeks 24 compared to day 0. | 
| Assessment of analgesic drug unit consumption based on clinical diary | Assessment of analgesic drug unit consumption based on clinical diary at time day 0, week one, week 2, week 6, week 10 and week 24. [Celecoxib 200mg cpr 1 tablet/day will be used as pain killer, in case of pain onset/recurrence; if subject is hypertensive or intolerant Paracetamol 1000mg cpr 2 tablets/day]. | Day 0, weeks 1, weeks 2 , 6 weeks, weeks 10 and weeks 24. | 
| Evaluation of adverse events (AE/SAE/SUSAR). | Assessment of the fraction of subjects leaving the Study early in relation to Adverse Events (AE/SAE/SUSAR). | Day 0, weeks 1, weeks 2 , weeks 6, weeks 10 and weeks 24. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MD-Tissue Collagen Medical, Ecoguide, Biomechanical, Modified Harris Hip Score, Numeric Rating Scale, Type I collagen