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

December 28, 2018 updated by: Istituto Clinico Humanitas

Subchondral and Intra-articular Application of Bone Marrow Concentrate as a Treatment Strategy for Knee Unicompartmental Osteoarthritis (OA): a Pilot Trial

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

25

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Milano
      • Rozzano, Milano, Italy, 20089
        • Recruiting
        • Istituto Clinico Humanitas
        • Contact:
          • Berardo Di Matteo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
baseline vs 12 months' follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
baseline vs 12 months' follow-up
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.
baseline vs 12 months' after treatment
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)
baseline vs 12 months' follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Clinico Humanitas

Investigators

  • Principal Investigator: Elizaveta Kon, MD, Istituto Clinico Humanitas, Rozzano, Italy
  • Study Director: Berardo Di Matteo, MD, Istituto Clinico Humanitas, Rozzano, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2019

Primary Completion (Anticipated)

July 1, 2021

Study Completion (Anticipated)

November 1, 2021

Study Registration Dates

First Submitted

December 22, 2018

First Submitted That Met QC Criteria

December 28, 2018

First Posted (Actual)

December 31, 2018

Study Record Updates

Last Update Posted (Actual)

December 31, 2018

Last Update Submitted That Met QC Criteria

December 28, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 172797

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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