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Subchondral and Intra-articular Application of Bone Marrow Concentrate for Knee Unicompartmental OA (MarrowMule)

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ClinicalTrials.gov Identifier: NCT03790189
Recruitment Status : Recruiting
First Posted : December 31, 2018
Last Update Posted : December 31, 2018
Sponsor:
Information provided by (Responsible Party):
Istituto Clinico Humanitas

Tracking Information
First Submitted Date  ICMJE December 22, 2018
First Posted Date  ICMJE December 31, 2018
Last Update Posted Date December 31, 2018
Estimated Study Start Date  ICMJE January 2019
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 28, 2018)
Change in IKDC (International Knee Documentation Committee) subjective score [ Time Frame: baseline vs 12 months' follow-up ]
IKDC subjective score is a validated clinical questionnaire (available also in Italian) designed to assess the functional status of the knee by a series of 10 items. The IKDC subjective score assess the overall function of the knee as subjectively evaluated by the patient who needs to answer a series of questions concerning symptoms and his/her activity level. It ranges from 0 to 100 points, with higher values representing a better knee status.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: December 28, 2018)
  • Variation in KOOS (Knee Injury and Osteoarthritis Outcome) Score [ Time Frame: baseline vs 12 months' follow-up ]
    KOOS score is a validated clinical questionnaire (available also in Italian) designed to assess the functional status of the knee by a series of 42 items. KOOS score consists of five sub-scales (Pain, Symptoms, Activity of Daily life, Sport, Quality of Life). The total score is obtained by summing the score of each sub-scale (max 21 point for Pain, 17 points for Symptoms, 41 points for Activity of daily life, 12 points for Sport, 9 points for Quality of Life). The total score's range is 0-100 and higher values represents better knee status.
  • VAS (Visual Analogue Scale) for pain [ Time Frame: baseline vs 12 months' after treatment ]
    Visual Analogue Scale to evaluate average knee pain during daily life. Range is from 0 to 100 and higher values represent higher pain perceived by the patient.
  • MRI (Magnetic Resonance Imaging) Changes in subchondral bone edema and cartilage status from basal to 12 months' follow-up [ Time Frame: baseline vs 12 months' follow-up ]
    MRI of the index knee will be performed to assess if the bone marrow concentrate was able to produce any effect on the subchondral bone edema and/or articular cartilage. To this purpose, the WORMS (Whole Organ Magnetic Resonance Imaging Score) will be adopted. This score allows to evaluate: 1) the amount of bone marrow edema (0-3 scale based on the extension of the bone marrow edema in the anatomical region considered, with higher value representing bigger bone marrow edema); 2) the cartilage damage (0 to 6 scale with higher values representing worse cartilage status)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Subchondral and Intra-articular Application of Bone Marrow Concentrate for Knee Unicompartmental OA
Official Title  ICMJE Subchondral and Intra-articular Application of Bone Marrow Concentrate as a Treatment Strategy for Knee Unicompartmental Osteoarthritis (OA): a Pilot Trial
Brief Summary

Unicompartmental knee osteoarthritis (OA) is a common finding especially in patients with lower limb malalignment and previous meniscectomy. Among the various treatment options, in recent years there has been an increasing attention towards the use of biologic agents, such as platelet rich plasma and mesenchymal stem cells, as intra-articular injective approaches to relieve pain and restore joint function. Anyway, the sole intra-articular administration of these agents may not lead to satisfactory outcome in a relevant percentage of patients. In fact, unicompartmental osteoarthritis is not only characterized by degeneration of the articular cartilage, but also by pathologic changes in the subchondral bone, both at the tibial plateaux and in the femoral condyle. Magnetic resonance imaging reveals, in many cases, alterations of the subchondral tissue known as "bone marrow edema", which is a sign of bone overload and play a significant role in the progression of unicompartmental OA and is responsible of OA-related symptoms. Therefore, concurrent treatment of both the subchondral bone damage and intra-articular degeneration could led to better outcome for patients affected by unicompartmental OA: the aim of the present pilot trial is to assess the safety and describe the clinical outcome following concurrent intra-articular and subchondral bone application of Bone Marrow Concentrate (BMC). BMC is an autologous product rich in mesenchymal stem cells, which have immuno-modulatory and throfic properties and are able to restore the joint homeostasis by reducing the inflammatory distress traditionally associated to OA.

BMC will be collected directly in the operating room from the anterior iliac crest or the tibia by using the MARROW CELLUTION kit (Geistlich, Switzerland), which allows to obtain BMC without the need of centrifugation processes. Approximately 9-10 ml of BMC will be harvested: 6 ml will be injected, under fluoroscopic guidance, in the tibial emiplateaux (approx 3 ml) and in the femoral condyle (approx 3 ml) presenting MRI evidence of bone marrow edema. The remaining amount of BMC will be administered intra-articularly to address articular tissues (cartilage, menisci and synovium). Twenty-five patients affected by unicompartmental knee OA will be included in the present pilot trial and treated in a "Day-Surgery" regimen. They will be followed up at 3, 6, and 12 months' after treatment by clinical questionnaires and radiographic evaluations (x-rays at 6 and 12 months, MRI at 12 months' f-up). Any intra-op and post-op adverse events will be documented.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Osteoarthritis, Knee
  • Cartilage Degeneration
Intervention  ICMJE Biological: Subchondral and intra-articular injection of BMC
Bone Marrow concentrate will be injected intra-articularly and at the bone-cartilage interface both in the tibia and femur of patients affected by unicompartmental knee osteoarthritis
Study Arms  ICMJE Experimental: Bone Marrow Concentrate
Bone Marrow concentrate will be injected intra-articularly and at the bone-cartilage interface both in the tibia and femur of patients affected by unicompartmental knee osteoarthritis
Intervention: Biological: Subchondral and intra-articular injection of BMC
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 28, 2018)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • chronic symptomatic (at least 6 months) medial or lateral unicompartmental OA of the knee, with Kellgren-Lawrence Score evaluated at x-rays= 2 or 3;
  • MRI evidence of "bone marrow edema" affecting the subchondral bone of the tibial emiplateaux and femoral condyle;
  • failure of previous conservative treatments in the same knee (e.g: pharmacological therapy, physiotherapy, previous intra-articular injections, etc..);
  • willingness to participate in the trial, including all follow-up visits and radiographic examinations.

Exclusion Criteria:

  • medial or lateral unicompartmental OA with Kellgren-Lawrence score= 1 or 4 (i.e. early osteoarthritis or end-stage osteoarthritis);
  • no MRI evidence of bone marrow edema in the affected knee compartment;
  • concurrent rheumatic or other immunological diseases;
  • concurrent malignancies;
  • bilateral symptomatic knee OA;
  • concurrent patello-femoral OA;
  • BMI>35
  • any surgical treatment in the index knee within 12 months from the screening visit.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Berardo Di Matteo, MD +390282245425 berardo.dimatteo@gmail.com
Contact: Laura Lovato, MS laura.lovato@hunimed.eu
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03790189
Other Study ID Numbers  ICMJE 172797
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Istituto Clinico Humanitas
Study Sponsor  ICMJE Istituto Clinico Humanitas
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Elizaveta Kon, MD Istituto Clinico Humanitas, Rozzano, Italy
Study Director: Berardo Di Matteo, MD Istituto Clinico Humanitas, Rozzano, Italy
PRS Account Istituto Clinico Humanitas
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP