Effect of Biophysical Stimulation on Intraspongious Bone Edema in Anterior Cruciate Ligament Reconstruction
Condition: ACL Injury; Pain; Magnetic Field Exposure
MeSH terms: Anterior Cruciate Ligament Injuries
Study type: Interventional

Summary: 
      The following study has as main objective to evaluate whether the use of I-ONE® therapy can
      reduce post-operative pain thanks to the modulation of inflammation in patients with bone
      bruise on the knee after anterior cruciate ligament (ACL) injury if applied 15 days before
      and 60 days after ACL reconstruction surgery for 4 hours a day compared to a control group
      (no-treatment). Both groups will be able to take anti-inflammatory drugs for pain control as
      per normal clinical practice.

      The secondary objective of the study are: quantify the reduction in the size of the bone
      bruise area, improving the level of knee function and the amount of anti-inflammatory drugs
      used in the aforementioned patients in the postoperative period compared to a control group.
    

Detailed description: 
      Articular cartilage, similarly to bone tissue, has a high sensitivity to physical stimuli and
      it has been shown that these are able to significantly modify the cartilage metabolism. There
      are several methods for applying a physical stimulus to articular cartilage: direct current,
      pulsed electromagnetic fields, electric fields and ultrasound. In vitro, all techniques have
      been shown to influence the metabolism of isolated chondrocytes. In vivo and in the clinic,
      the use of the biophysical stimulus for the treatment of the joint must respond to the need
      to treat the articular cartilage in its total extension and thickness, in addition to
      involving the joint structures, for example meniscus, ligaments, synovial membrane up to to
      the subchondral bone.

      To date, these problems have been solved exclusively with the use of specific pulsed
      electromagnetic fields I-ONE®, as well demonstrated in the CRES study (Cartilage Repair and
      Electromagnetic Stimulation). In vitro, I-ONE® therapy produces a significant increase both
      in the proliferation of chondrocytes in the presence of Insulin growth factors- 1 (IGF-1),
      and in the synthesis of proteoglycans, also in the presence of inflammatory phenomena in the
      breeding ground, such as Interleukin 1B (IL-1B).

      In vitro studies on neutrophils, synoviocytes and chondrocytes have shown that I-ONE® therapy
      increases the availability of adenosine A2A receptors and, acting as chondroprotective drugs,
      reduces tissue damage due to the inflammatory response. These results have been demonstrated
      in animal models of osteoarthritis where, stimulation with I-ONE® therapy led to a reduction
      in the progression of osteoarthritic knee injuries. In sheep undergoing osteochondral
      transplantation, I-ONE® therapy has been able to favor the formation of new subchondral
      tissue, decreasing the areas of resorption and avoiding its complete resorption. A high
      synthesis of anabolic factors, such as Transforming growth factor beta (TGF-β), and an
      inhibition of the synthesis of pro-inflammatory cytokines such as the Tumor necrosis factor
      alfa (TNF-α) and Interleukin 1 beta (IL-1β) have been observed as evidence of an anabolic and
      trophic effect. In rabbits subjected to osteochondral lesions, I-ONE® therapy has proven
      effective in significantly improving the quality of both bone and cartilage regenerated
      tissue in osteochondral defects in the presence of collagen scaffolds and Mesenchymal Stem
      Cells (MSCs). MSCs have the potential to differentiate into a chondrocyte phenotype however
      the presence of pro-inflammatory cytokines in particular IL-1β is able to inhibit
      chondrogenesis.

      The anti-inflammatory activity of I-ONE® therapy effectively counteracted the degenerative
      effect of IL-1β by significantly improving cartilage regeneration compared to unstimulated
      lesions. This explains, even in vivo, the anti-degenerative, reparative and anti-inflammatory
      effect of treatment with I-ONE® therapy. In the clinical practice, I-ONE® therapy is able to
      prevent and/or slow down the degenerative phenomena that follow surgical operations. The
      latter result has been demonstrated both in patients undergoing anterior cruciate ligament
      reconstruction, and in patients with cartilage lesions treated with arthroscopic
      microfractures, in patients undergoing ONE STEP method with bone marrow concentrate and
      scaffold, and in patients undergoing total knee prosthesis with or without patellar
      resurfacing. All clinical studies have shown a reduction in NSAID intake and an anticipated
      functional recovery time in patients treated with I-ONE® therapy compared to those belonging
      to the non-treatment group. Also in the conservative treatment of joint pathologies, such as
      spontaneous osteonecrosis and knee osteoarthritis in the initial stagE I-ONE® therapy has
      proven effective in reducing the bone area marrow edema and in improving the functional
      recovery of the joint. Both in conservative and post-surgical treatment, the results were
      maintained even in the long term (follow-up 2 and 3 years after the treatment).

      Similar results have been found after treatment with I-ONE® therapy in patients with
      patello-femoral pain, a frequent pathology in sports, especially in women, whose
      etiopathogenesis is controversial and attributable to several factors, including a
      malalignment of the joint, a dysplasia of the patella or of the femoral trochlea. The
      anterior knee pain, which accompanies this pathology, can become chronic over time and become
      highly limiting for sports. I-ONE® therapy has proven effective in promoting joint function,
      resolving painful symptoms and promoting a rapid return to sports, maintaining the result
      over a year. I-ONE® is an easy-to-use therapy that eliminates the possible side effects that
      characterize drug therapy and its use is well accepted by patients. Since cartilage
      degeneration is an irreversible process, it is essential to intervene early with an effective
      chondroprotective treatment, which is able to maintain an intact cartilage in the long run
      while also preserving the quality of the subchondral bone tissue (of fundamental importance
      for the survival of the articular cartilage).

      In conclusion, the control of the joint microenvironment, by means of a non-invasive method,
      such as the biophysical stimulus, constitutes an important therapeutic possibility, which
      assumes a great importance in the presence of osteo-cartilaginous pain in the knee. In about
      70% of the lesions of the anterior cruciate ligament (ACL), the presence of trabecular
      microfractures due to the impact of the subchondral bone, called bone bruises, is associated.
      These are characterized by the presence of hemorrhage, edema, necrosis and fibrosis: they are
      most frequently located in the external compartment of the knee (most often in the lateral
      femoral condyle) and associated with intense pain (accentuated by the weight-bearing). These
      lesions tend to reabsorb very slowly and cause intense pain especially during the
      post-operative period in ACL reconstruction, with limitation and lengthening of recovery
      times. This is mainly due to the difficulty of weight-bearing during the first post-operative
      month.

      The following study has as main objective to evaluate whether the use of I-ONE® therapy can
      reduce post-operative pain thanks to the modulation of inflammation in patients with bone
      bruise on the knee after anterior cruciate ligament (ACL) injury if applied 15 days before
      and 60 days after ACL reconstruction surgery for 4 hours a day compared to a control group
      (no-treatment). Both groups will be able to take anti-inflammatory drugs for pain control as
      per normal clinical practice.

      The secondary objective of the study are: quantify the reduction in the size of the bone
      bruise area, improving the level of knee function and the amount of anti-inflammatory drugs
      used in the aforementioned patients in the postoperative period compared to a control group.

      I-ONE® therapy will be initiated in the 15 days preceding the ACL reconstruction surgery and
      in the first 60 days following the surgery, only in the treatment group. The control group
      will not be treated with I-ONE® devices (no-treatment). Paracetamol 1000 mg will be supplied
      to both groups, to be taken for pain control as per normal clinical practice.Drugs and I-ONE®
      devices will be delivered to the patient on the day of the pre-hospitalization visit which
      takes place routinely 15 days before the surgery. Clinical assessments using rating scales
      will be performed in both groups on the day of the pre-hospitalization visit, immediately
      before ACL reconstruction and during outpatient visit at 1, 2, 4, 12 and 24 months after ACL
      reconstruction. Magnetic resonance imaging will be performed 2, 4 and 12 months after surgery
      to highlight both the integration of the pro-ACL graft and the reduction of the bone bruise
      area. In particular, to quantify the resolution of the bone bruise area expected in the
      treatment group, the magnetic resonance performed 2 months after surgery will be used.
    

Intervention name(s): I-ONE® therapy; Anti-inflammatory drug
Intervention type(s): Device; Drug
Intervention description(s): I-ONE® therapy will be used in patients with bone bruise on the knee after anterior cruciate ligament (ACL) injury 15 days before and 60 days after ACL reconstruction surgery for 4 hours a day compared to a control group (no-treatment).; Pain before and after ACL reconstruction will be managed with common anti-inflammatory drugs (Paracetamol)
Other intervention name(s): I-ONE® IGEA
Intervention MeSH terms: Anti-Inflammatory Agents
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: bone bruise; pain; ACL reconstruction