Knee OsteoarthritisBone-GunNCT04310852
Knee Osteoarthritis Treatment With Percutaneous Injections of Autologous Bone Marrow Concentrate
An observational study of Knee Osteoarthritis and Cartilage Degeneration, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
Recently there has been a growing interest in the role of subchondral bone in knee arthritis, both in its etiology and evolution and in its clinical significance. It has now been widely demonstrated that changes in the subchondral bone can develop both as a cause and as a consequence of joint degeneration and it is… Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Knee Osteoarthritis, Cartilage Degeneration
- What is being tested?
- BioCue Concentration Kit
- Type of treatment
- Medical device
- How many people
- 25 participants
- Where
- 1 siteItaly
- Study dates
- 6 Jun 2018to 31 Jan 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 25 patients, meeting specific inclusion and exclusion criteria, will be enrolled. In general, the patients are characterized as patients with painful arthritis of the medial or lateral compartment, which have not achieved a reduction in pain in the presence of conservative treatments. The patients are enrolled on the basis of a paper questionnaire based on the inclusion and exclusion criteria: a patient can only be enrolled if he or she responds positively to all questions related to the inclusion criteria and negatively to all questions related to the exclusion criteria.
Who may be able to join
- Male or female patients aged between 40 and 70;
- Medial or lateral arthrosis (grade 2-3 according to Kellgren-Lawrence score);
- Failure after at least 6 months of conservative treatment (patients not responding to drug therapy with NSAIDs and painkillers, no benefit from rehabilitation cycle in water or gym, no benefit after hyaluronic acid or platelet-rich plasma (PRP) infiltrations, or after at least one infiltration of corticosteroids);
- Ability and consent of patients to participate actively in the rehabilitation and clinical and radiological follow-up protocol;
- Signing of informed consent.
Who cannot join
- Patients who are incapable of understanding and will;
- Trauma patients within 6 months prior to surgery;
- Patients with malignancies;
- Patients with rheumatic diseases;
- Patients with diabetes;
- Patients with metabolic thyroid disorders;
Show all 12Show fewer
- Patients abusing alcoholic beverages, drugs or drugs;
- Patients with lower limb impairment above 10°
- Body Mass Index <18 or > 35;
- Patients undergoing knee surgery during the 12 months prior to surgery;
- Patients with pathology ascribable to patellofemoral pathology;
- Untreated knee instability.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Humanitas Research Hospital
Rozzano, Milan, 20089
Elizaveta Kon, MD, +390282247523
About this study
Official title: Pilot Study on the Treatment of Knee Osteoarthritis With Percutaneous Injections of Autologous Bone Marrow Concentrate at the Cartilage-bone Interface.
Recently there has been a growing interest in the role of subchondral bone in knee arthritis, both in its etiology and evolution and in its clinical significance. It has now been widely demonstrated that changes in the subchondral bone can develop both as a cause and as a consequence of joint degeneration and it is now accepted in the scientific community that the presence of these changes is of clinical importance, causing pain and an inflammatory state that can contribute to the evolution of arthrosis arthropathy. Recently the use of mesenchymal cells obtained from the bone marrow has been proposed for the treatment of gonarthrosis by intra-articular injections. Even more recently, treatments have been studied and proposed for the treatment of the bone-cartilage interface in knees affected by osteoarthrosis, using autologous bone marrow concentrate, with promising results.
Read the detailed description
Osteoarthritis (OA) is a chronic degenerative and disabling disease of joint joints, in which metabolic impairment between the synthesis and degradation of cartilage and subchondral bone, involves progressive destruction of joint tissue accompanied by chronic pain and synovial inflammation. Currently, available therapies are mostly palliative and designed to mask symptoms. The study proposed here has been constructed on the basis of the scientific evidence reported in the literature regarding the etiology and the treatment of OA. As recently demonstrated, the use of mesenchymal cells obtained from the bone marrow was effective in the treatment of gonarthrosis by intra-articular injections. Even more recently, treatments aimed at treating the bone-cartilage interface in arthritic knees have been studied and proposed. In the 2016 Val et al. pilot study, stem cells from the tibial bone marrow injected into the percutaneous bone-cartilage interface were described as a new therapeutic approach to osteoarthritis of the knee. This procedure is able to repair cartilage by stimulating subchondral bone angiogenesis and alleviating ischemia associated with arthritic knee pain, generating extremely positive outcomes in patients with low-grade osteoarthritis and relieving long-term pain in patients with high-grade osteoarthritis. This treatment is also able to induce differentiation and proliferation of chondrocytes, leading to an increase in the size of the intra-articular matrix, demonstrating an effective and minimally invasive treatment for the resolution of OA. The study described here aims to evaluate the potential effectiveness of the synergistic effect of both injections, with the aim of improving the symptomatic picture of patients with OA of the knee. Combining percutaneous injections at the bone-cartilage interface with intra-articular injections will provide proven results for the use of stem cells such as cartilage repair, increased vascularity, and pain reduction, in both compartments of the knee affected by OA. The positive effects reported in the literature regarding intra-articular injections will be combined with those reported with respect to the use of percutaneous injections at the cartilage, in order to obtain a better outcome in the treatment of the disease than in previous studies.
- Conditions
- Knee Osteoarthritis, Cartilage Degeneration
- Being tested
- BioCue Concentration Kit
- Keywords
- arthritis, knee, bone marrow concentrate
- Medical subject headings
- Osteoarthritis, Knee, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BioCue Concentration KitDevice
The treatment will be carried out in the operating room under ordinary hospitalization and involves the application of 9 ml of autologous bone marrow concentrate in the knee affected by arthrosis. Specifically, 3 ml will be applied at the level of the bone-cartilage interface of the femur, 3 ml at the level of the bone-cartilage interface of the tibia, and 3 ml will be injected into the joint for a simultaneous action also at the level of the cartilage. To obtain the necessary amount of bone marrow concentrate, an aspirate of bone marrow will be taken from the iliac crest (60 ml) and homolateral tibia (30 ml) of the patient and concentrated by BioCue Concentration Kit, company Zimmer biomet, and centrifuge. This autologous bone marrow concentrate will be injected by means of the Perfuse at the level of the tibial and femoral bone-cartilage interface of the percutaneous arthrosis affected compartment under radiographic control.
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of subjective International Knee Documentation Committee (IKDC)
The IKDC subjective knee Form consists of questions, divided into four sections: Symptoms, Functionality during daily activities and sports, Current knee function, Participation in work and sports. The patient will fill the subjective IKDC questionnaire.
Measured: up to 24 months
Secondary outcomes (5)
improvement according to the subscale Knee injury and Osteoarthritis Outcome Score (KOOS) pain
The KOOS score consists of 5 categories; Pain, Other symptoms, Functionality in daily activities, Functionality in sports and recreational activities, and Quality of life. The previous week shall be taken into account as a reference at the time of compilation. For each question, several answer options are provided within each category, corresponding to a score between 0-4 points; overall the score is between 100 and 0 (100 indicates absence of symptoms, 0 indicates total presence of symptoms). The patient will fill the KOOS questionnaire.
Measured: up to 24 months
improvement of the overall KOOS
The KOOS score consists of 5 categories; Pain, Other symptoms, Functionality in daily activities, Functionality in sports and recreational activities, and Quality of life. The previous week shall be taken into account as a reference at the time of compilation. For each question, several answer options are provided within each category, corresponding to a score between 0-4 points; overall the score is between 100 and 0 (100 indicates absence of symptoms, 0 indicates total presence of symptoms). The patient will fill the KOOS questionnaire.
Measured: up to 24 months
improvement of the TEGNER score
This score allows to estimate the level of motor activity of a subject with a score between 0 and 10 (0 represents 'incapacity' and 10 represents 'participation in competitive sports'). In the study the TEGNER Score will be compiled directly by the Investigator, through an interview to the patient.
Measured: up to 24 months
Improvement according to Whole-Organ Magnetic Resonance Imaging Score (WORMS) MRI score
The WORMS score is composed of seven voices that describe in the complex, the aspect of the joint, evaluating specifically the state of the cartilage with sequences T2-weighted FSE and FS-3D SPGR (taking into consideration thickness and signal) presence of subchondral cysts with suppressed fat sequences T2-weighted FSE, presence of subchondral edema with suppressed fat sequences T2-weighted FSE, joint profile (considering any flattening or depression of the articular surface compared to normal), the presence of osteophytes and their size, the state of the meniscus, both medial and lateral, the state of the synovia by distension of the synovial cavity. The radiologist will fill the WORMS score forms.
Measured: up to 24 months
Improvement according to Kellgren-Lawrence (K/L) score
The score K/L grading scale allows to classify and differentiate the degree of severity of osteoarthritis of the damaged knee. The score includes grade I to grade IV (the higher the grade, the more severe the OA). The radiologist will fill K/L score forms.
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2020
- Study start6 Jun 2018
- Primary completion30 Sep 2021 (estimated)
- Study completion31 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- More trials run by Istituto Clinico HumanitasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elizaveta Kon, MD, Principal investigator, Istituto Clinico Humanitas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04310852
- Sponsor's protocol ID
- 528
- Acronym
- Bone-Gun
- Status last verified
- Mar 2020
- First submitted
- 10 Mar 2020
- Last updated
- 17 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study on the Treatment of Knee Osteoarthritis With Percutaneous Injections of Autologous Bone Marrow Concentrate at the Cartilage-bone Interface.
- ClinicalTrials.gov ID
- NCT04310852
- Acronym / sponsor ID
- Bone-Gun / 528
- Conditions
- Knee Osteoarthritis, Cartilage Degeneration
- Keywords
- arthritis, knee, bone marrow concentrate
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Study start
- 6 Jun 2018 (actual)
- Primary completion
- 30 Sep 2021 (estimated)
- Study completion
- 31 Jan 2022 (estimated)
- First posted
- 17 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recently there has been a growing interest in the role of subchondral bone in knee arthritis, both in its etiology and evolution and in its clinical significance. It has now been widely demonstrated that changes in the subchondral bone can develop both as a cause and as a consequence of joint degeneration and it is now accepted in the scientific community that the presence of these changes is of clinical importance, causing pain and an inflammatory state that can contribute to the evolution of arthrosis arthropathy. Recently the use of mesenchymal cells obtained from the bone marrow has been proposed for the treatment of gonarthrosis by intra-articular injections. Even more recently, treatments have been studied and proposed for the treatment of the bone-cartilage interface in knees affected by osteoarthrosis, using autologous bone marrow concentrate, with promising results.
Detailed description
Osteoarthritis (OA) is a chronic degenerative and disabling disease of joint joints, in which metabolic impairment between the synthesis and degradation of cartilage and subchondral bone, involves progressive destruction of joint tissue accompanied by chronic pain and synovial inflammation. Currently, available therapies are mostly palliative and designed to mask symptoms. The study proposed here has been constructed on the basis of the scientific evidence reported in the literature regarding the etiology and the treatment of OA. As recently demonstrated, the use of mesenchymal cells obtained from the bone marrow was effective in the treatment of gonarthrosis by intra-articular injections. Even more recently, treatments aimed at treating the bone-cartilage interface in arthritic knees have been studied and proposed. In the 2016 Val et al. pilot study, stem cells from the tibial bone marrow injected into the percutaneous bone-cartilage interface were described as a new therapeutic approach to osteoarthritis of the knee. This procedure is able to repair cartilage by stimulating subchondral bone angiogenesis and alleviating ischemia associated with arthritic knee pain, generating extremely positive outcomes in patients with low-grade osteoarthritis and relieving long-term pain in patients with high-grade osteoarthritis. This treatment is also able to induce differentiation and proliferation of chondrocytes, leading to an increase in the size of the intra-articular matrix, demonstrating an effective and minimally invasive treatment for the resolution of OA. The study described here aims to evaluate the potential effectiveness of the synergistic effect of both injections, with the aim of improving the symptomatic picture of patients with OA of the knee. Combining percutaneous injections at the bone-cartilage interface with intra-articular injections will provide proven results for the use of stem cells such as cartilage repair, increased vascularity, and pain reduction, in both compartments of the knee affected by OA. The positive effects reported in the literature regarding intra-articular injections will be combined with those reported with respect to the use of percutaneous injections at the cartilage, in order to obtain a better outcome in the treatment of the disease than in previous studies.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 25 patients, meeting specific inclusion and exclusion criteria, will be enrolled. In general, the patients are characterized as patients with painful arthritis of the medial or lateral compartment, which have not achieved a reduction in pain in the presence of conservative treatments. The patients are enrolled on the basis of a paper questionnaire based on the inclusion and exclusion criteria: a patient can only be enrolled if he or she responds positively to all questions related to the inclusion criteria and negatively to all questions related to the exclusion criteria.
Key inclusion criteria (5 listed)
- Male or female patients aged between 40 and 70;
- Medial or lateral arthrosis (grade 2-3 according to Kellgren-Lawrence score);
- Failure after at least 6 months of conservative treatment (patients not responding to drug therapy with NSAIDs and painkillers, no benefit from rehabilitation cycle in water or gym, no benefit after hyaluronic acid or platelet-rich plasma (PRP) infiltrations, or after at least one infiltration of corticosteroids);
- Ability and consent of patients to participate actively in the rehabilitation and clinical and radiological follow-up protocol;
- Signing of informed consent.
Key exclusion criteria (12 listed)
- Patients who are incapable of understanding and will;
- Trauma patients within 6 months prior to surgery;
- Patients with malignancies;
- Patients with rheumatic diseases;
- Patients with diabetes;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BioCue Concentration KitThe treatment will be carried out in the operating room under ordinary hospitalization and involves the application of 9 ml of autologous bone marrow concentrate in the knee affected by arthrosis. Specifically, 3 ml will be applied at the level of the bone-cartilage interface of the femur, 3 ml at the level of the bone-cartilage interface of the tibia, and 3 ml will be injected into the joint for a simultaneous action also at the level of the cartilage. To obtain the necessary amount of bone marrow concentrate, an aspirate of bone marrow will be taken from the iliac crest (60 ml) and homolateral tibia (30 ml) of the patient and concentrated by BioCue Concentration Kit, company Zimmer biomet, and centrifuge. This autologous bone marrow concentrate will be injected by means of the Perfuse at the level of the tibial and femoral bone-cartilage interface of the percutaneous arthrosis affected compartment under radiographic control. | Device | – |
Primary outcome
Improvement of subjective International Knee Documentation Committee (IKDC)
Time frame: up to 24 months
The IKDC subjective knee Form consists of questions, divided into four sections: Symptoms, Functionality during daily activities and sports, Current knee function, Participation in work and sports. The patient will fill the subjective IKDC questionnaire.
5 secondary outcomes
improvement according to the subscale Knee injury and Osteoarthritis Outcome Score (KOOS) pain
Time frame: up to 24 months
improvement of the overall KOOS
Time frame: up to 24 months
improvement of the TEGNER score
Time frame: up to 24 months
Improvement according to Whole-Organ Magnetic Resonance Imaging Score (WORMS) MRI score
Time frame: up to 24 months
Improvement according to Kellgren-Lawrence (K/L) score
Time frame: up to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizaveta Kon, MD principal investigator
Istituto Clinico Humanitas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Knee Osteoarthritis and Cartilage Degeneration, run by Istituto Clinico Humanitas at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Elizaveta Kon, MD (+390282247523, elizaveta.kon@humanitas.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement of subjective International Knee Documentation Committee (IKDC) (time frame: up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2020.