Ignite Creation Date:
2024-06-16 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06459817
Status:
RECRUITING
Last Update Posted:
2024-07-03
First Post:
2024-05-23
Brief Title:
Quantitative Assessment of BB-02 Therapy Effect on Cartilage Status in Patients Affected by Early Knee Osteoarthritis
Sponsor:
Istituto Ortopedico Rizzoli
Organization:
Istituto Ortopedico Rizzoli
Study Overview
Official Title:
Quantitative Assessment of BB-02 Therapy Effect on Cartilage Status in Patients Affected by Early Knee Osteoarthritis
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
JOCARE-OA
Brief Summary:
Knee osteoarthritis is a condition that affects young or middle-aged patients with high functional demands Knee replacement surgery in patients under 65 years of age is associated with a high risk of failure and the need for revision For this reason it becomes crucial to identify treatment alternatives aimed primarily at resolving symptoms but also at slowing down the joint degenerative process with the goal of delaying the need for prosthetic treatment as much as possible The medical device BB-02 IGEA SpA Carpi Italy is a certified medical device according to Regulation EU 2017745 MDR for the treatment of inflammatory and degenerative tissue pathologies and represents an effective tool in the treatment of early and intermediate osteoarthritis To date the demonstration of the efficacy of BB-02 therapy has been measured through the evaluation of clinical endpoints using both objective and subjective assessment scales So far there is a lack of instrumental measurement of the ability of BB-02 therapy to preserve the integrity of the articular cartilage
The primary objective of the study is to evaluate through magnetic resonance imaging MRI the effect of pulsed electromagnetic fields administered via BB-02 therapy on cartilage damage in subjects with early-stage osteoarthritis The BB-02 device was chosen based on promising results reported in the pre-clinical phase of experimentation
The secondary objective is to assess the effect of BB-02 therapy on pain resolution and clinical scores of knee functionality in the two different therapeutic regimens
The primary objective of the study is to evaluate through magnetic resonance imaging MRI the effect of pulsed electromagnetic fields administered via BB-02 therapy on cartilage damage in subjects with early-stage osteoarthritis The BB-02 device was chosen based on promising results reported in the pre-clinical phase of experimentation
The secondary objective is to assess the effect of BB-02 therapy on pain resolution and clinical scores of knee functionality in the two different therapeutic regimens
Detailed Description:
Knee osteoarthritis gonarthrosis is an extremely debilitating condition for affected patients who experience progressive functional limitations with consequent impairment of daily activities and quality of life Additionally this condition represents a significant burden on the national healthcare system due to the severe functional limitations of affected patients and the high costs of interventions and devices used for prosthetic replacement Knee replacement surgery is the gold standard treatment for gonarthrosis however this procedure carries a doubled risk of failure in patients under 60 years of age Therefore considering the high number of patients affected by early or intermediate-stage osteoarthritis at an age characterized by high functional demands it becomes essential to identify treatment alternatives aimed primarily at resolving symptoms but also at slowing down the degenerative joint process with the goal of delaying the need for prosthetic treatment as much as possible
While various surgical solutions including joint preservation procedures have been proposed clear evidence is still lacking regarding the effectiveness of conservative treatments in protecting and possibly regenerating the pathological articular cartilage that characterizes patients with gonarthrosis In this scenario quantifying the therapeutic potential of non-surgical treatment devices for patients with gonarthrosis is of considerable importance in the development of degenerative joint disease treatment From this need arises the desire to verify the regenerative potential of available strategies for the treatment of joint pathologies
Biophysical stimulation with variable intensity magnetic fields over time represents a therapeutic option supported by a solid body of scientific literature for the treatment of conditions associated with joint osteoarthritis such as bone edema and soft tissue distress The medical device BB-02 IGEA SpA Carpi Italy is a certified medical device according to Regulation EU 2017745 MDR for the treatment of inflammatory and degenerative tissue diseases BB-02 is used for inflammation control and chondroprotection chondroprotection refers to the set of pharmacological physical surgical alone or combined treatments aimed at preserving cartilage integrity or limiting damage due to degenerative pathological and traumatic processes as well as inflammatory reactions BB-02 therapy limits the degenerative effects of inflammation present in the joint environment after trauma or surgery The medical device BB-02 extinguishes joint inflammation through an adenosine agonist action on the A2A receptor and exerts a strong chondroprotective effect Extensive translational research has shown that biophysical stimulation with BB-02 therapy is capable of modulating cartilage metabolism Massari L 2007
In vitro BB-02 therapy induces a significant increase in both chondrocyte proliferation in the presence of growth factors such as IGF-1 and proteoglycan synthesis even in the presence of inflammatory phenomena such as IL-1β De Mattei M 2003 2004 2009 Ongaro A 2011 Veronesi 2015 In vitro studies on neutrophils synoviocytes and chondrocytes have shown that BB-02 therapy increases the availability of adenosine A2A receptors and acting as chondroprotective agents reduces tissue damage due to the inflammatory response Varani K 2002 2008 2017 Stimulation with BB-02 therapy by reducing the release of inflammation mediators involved in cartilage degeneration such as inflammatory cytokines IL-6 and IL-8 and lipid mediators of inflammation prostaglandin E2 enhances the anti-inflammatory effect of individual adenosinic agonists A2A and A3 by increasing the release of anti-inflammatory cytokines such as IL-10 Ongaro A 2012 Vincenzi F 2013 Synovial stem cells have shown a high chondrogenic potential in culture with appropriate chondroinductive supplements supplemented with TGF-β3 they are capable of differentiating in a chondrogenic direction In a study conducted on these types of cells chondrogenic differentiation was analyzed in the presence of inflammatory conditions obtained by adding the culture medium with IL-1β Ongaro A 2015 and BB-02 therapy Stimulation is able to inhibit the inflammatory phenomenon and preserve the chondrocyte phenotype These and other results have been confirmed in animal models of osteoarthritis where stimulation with BB-02 therapy has led to a reduction in the progression of osteoarthritic lesions in the knee Fini M 2005 2008 Veronesi F 2014 In sheep undergoing osteochondral transplantation BB-02 therapy was able to promote the formation of new subchondral bone tissue reducing areas of bone resorption avoiding complete implant resorption Benazzo F 2008 Evidence of an anabolic and trophic effect has been observed with high synthesis of anabolic factors such as TGF-β and inhibition of the synthesis of pro-inflammatory cytokines such as TNF-α and IL-1β In rabbits with osteochondral lesions BB-02 therapy has been shown to be effective in significantly improving the quality of regenerated tissue both bone and cartilage in osteochondral defects in the presence of collagen scaffolds and bone marrow concentrate BMC Veronesi F BMC Musculoskelet Disord 2015 The anti-inflammatory activity of BB-02 therapy effectively counteracts the degenerative effect of IL-1β significantly improving cartilage regeneration compared to non-stimulated lesions Recently the Columbia University group has demonstrated how BB-02 therapy is able to maximize the survival and functionality of osteochondral implants in tissue engineering methods Stefani RM 2020 In clinical practice in the conservative treatment of joint pathologies such as Bone Marrow Edema Martinelli N 2015 Perugia D 2015 spontaneous osteonecrosis of the knee Marcheggiani Muccioli G 2012 early-stage knee osteoarthritis Gobbi A 2013 and patellofemoral pathology Immarrone CS 2016 BB-02 therapy has been shown to be effective in resolving the area of bone marrow edema and improving joint functional recovery Imaging diagnostics in the study of cartilage pathology can non-invasively confirm the presence of cartilage pathology establish the degree of alterations enable proper therapy planning conservative or surgical and verify its effectiveness over time Conventional radiography X-ray is the most basic and cost-effective imaging technique and is used as a first-level investigation in the diagnosis of degenerative joint pathology but it is of limited use in evaluating early stages and initial alterations of articular cartilage The advent of magnetic resonance imaging MRI with its superior soft tissue contrast and multiplanar imaging capabilities has solved many problems in imaging articular cartilage providing non-invasive both morphological and biochemical information on the cartilage state Morphological information provided by MRI includes both focal and diffuse cartilage lesions MRI provides information such as thickness volume and three-dimensional morphology of the cartilage biochemical information is represented by the ability to determine the content of water proteoglycans and collagen Knowledge of this additional information is of great utility in understanding cartilage pathology and therefore in choosing therapeutic treatment
In this study we aim to evaluate the efficacy of two different therapeutic regimens with BB-02 therapy in patients still active in sports with initial cartilage damage The present study aims to observe the effect of BB-02 therapy on cartilage through high-field MRI 3 Tesla 3T investigation capable of providing both morphological and biochemical information on joint structures With 3T MRI we will evaluate the knee articular cartilage before and after treatment focusing on initial superficial lesions present before treatment and at the end of therapy assessing whether and to what extent they are repaired
Two different therapeutic regimens of BB-02 therapy will be applied in the study 4 hours a day for 30 days and 1 hour a day for 90 days
While various surgical solutions including joint preservation procedures have been proposed clear evidence is still lacking regarding the effectiveness of conservative treatments in protecting and possibly regenerating the pathological articular cartilage that characterizes patients with gonarthrosis In this scenario quantifying the therapeutic potential of non-surgical treatment devices for patients with gonarthrosis is of considerable importance in the development of degenerative joint disease treatment From this need arises the desire to verify the regenerative potential of available strategies for the treatment of joint pathologies
Biophysical stimulation with variable intensity magnetic fields over time represents a therapeutic option supported by a solid body of scientific literature for the treatment of conditions associated with joint osteoarthritis such as bone edema and soft tissue distress The medical device BB-02 IGEA SpA Carpi Italy is a certified medical device according to Regulation EU 2017745 MDR for the treatment of inflammatory and degenerative tissue diseases BB-02 is used for inflammation control and chondroprotection chondroprotection refers to the set of pharmacological physical surgical alone or combined treatments aimed at preserving cartilage integrity or limiting damage due to degenerative pathological and traumatic processes as well as inflammatory reactions BB-02 therapy limits the degenerative effects of inflammation present in the joint environment after trauma or surgery The medical device BB-02 extinguishes joint inflammation through an adenosine agonist action on the A2A receptor and exerts a strong chondroprotective effect Extensive translational research has shown that biophysical stimulation with BB-02 therapy is capable of modulating cartilage metabolism Massari L 2007
In vitro BB-02 therapy induces a significant increase in both chondrocyte proliferation in the presence of growth factors such as IGF-1 and proteoglycan synthesis even in the presence of inflammatory phenomena such as IL-1β De Mattei M 2003 2004 2009 Ongaro A 2011 Veronesi 2015 In vitro studies on neutrophils synoviocytes and chondrocytes have shown that BB-02 therapy increases the availability of adenosine A2A receptors and acting as chondroprotective agents reduces tissue damage due to the inflammatory response Varani K 2002 2008 2017 Stimulation with BB-02 therapy by reducing the release of inflammation mediators involved in cartilage degeneration such as inflammatory cytokines IL-6 and IL-8 and lipid mediators of inflammation prostaglandin E2 enhances the anti-inflammatory effect of individual adenosinic agonists A2A and A3 by increasing the release of anti-inflammatory cytokines such as IL-10 Ongaro A 2012 Vincenzi F 2013 Synovial stem cells have shown a high chondrogenic potential in culture with appropriate chondroinductive supplements supplemented with TGF-β3 they are capable of differentiating in a chondrogenic direction In a study conducted on these types of cells chondrogenic differentiation was analyzed in the presence of inflammatory conditions obtained by adding the culture medium with IL-1β Ongaro A 2015 and BB-02 therapy Stimulation is able to inhibit the inflammatory phenomenon and preserve the chondrocyte phenotype These and other results have been confirmed in animal models of osteoarthritis where stimulation with BB-02 therapy has led to a reduction in the progression of osteoarthritic lesions in the knee Fini M 2005 2008 Veronesi F 2014 In sheep undergoing osteochondral transplantation BB-02 therapy was able to promote the formation of new subchondral bone tissue reducing areas of bone resorption avoiding complete implant resorption Benazzo F 2008 Evidence of an anabolic and trophic effect has been observed with high synthesis of anabolic factors such as TGF-β and inhibition of the synthesis of pro-inflammatory cytokines such as TNF-α and IL-1β In rabbits with osteochondral lesions BB-02 therapy has been shown to be effective in significantly improving the quality of regenerated tissue both bone and cartilage in osteochondral defects in the presence of collagen scaffolds and bone marrow concentrate BMC Veronesi F BMC Musculoskelet Disord 2015 The anti-inflammatory activity of BB-02 therapy effectively counteracts the degenerative effect of IL-1β significantly improving cartilage regeneration compared to non-stimulated lesions Recently the Columbia University group has demonstrated how BB-02 therapy is able to maximize the survival and functionality of osteochondral implants in tissue engineering methods Stefani RM 2020 In clinical practice in the conservative treatment of joint pathologies such as Bone Marrow Edema Martinelli N 2015 Perugia D 2015 spontaneous osteonecrosis of the knee Marcheggiani Muccioli G 2012 early-stage knee osteoarthritis Gobbi A 2013 and patellofemoral pathology Immarrone CS 2016 BB-02 therapy has been shown to be effective in resolving the area of bone marrow edema and improving joint functional recovery Imaging diagnostics in the study of cartilage pathology can non-invasively confirm the presence of cartilage pathology establish the degree of alterations enable proper therapy planning conservative or surgical and verify its effectiveness over time Conventional radiography X-ray is the most basic and cost-effective imaging technique and is used as a first-level investigation in the diagnosis of degenerative joint pathology but it is of limited use in evaluating early stages and initial alterations of articular cartilage The advent of magnetic resonance imaging MRI with its superior soft tissue contrast and multiplanar imaging capabilities has solved many problems in imaging articular cartilage providing non-invasive both morphological and biochemical information on the cartilage state Morphological information provided by MRI includes both focal and diffuse cartilage lesions MRI provides information such as thickness volume and three-dimensional morphology of the cartilage biochemical information is represented by the ability to determine the content of water proteoglycans and collagen Knowledge of this additional information is of great utility in understanding cartilage pathology and therefore in choosing therapeutic treatment
In this study we aim to evaluate the efficacy of two different therapeutic regimens with BB-02 therapy in patients still active in sports with initial cartilage damage The present study aims to observe the effect of BB-02 therapy on cartilage through high-field MRI 3 Tesla 3T investigation capable of providing both morphological and biochemical information on joint structures With 3T MRI we will evaluate the knee articular cartilage before and after treatment focusing on initial superficial lesions present before treatment and at the end of therapy assessing whether and to what extent they are repaired
Two different therapeutic regimens of BB-02 therapy will be applied in the study 4 hours a day for 30 days and 1 hour a day for 90 days
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None