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Prospective Evaluation of PRP and BMC Treatment to Accelerate Healing After ACL Reconstruction

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ClinicalTrials.gov Identifier: NCT04205656
Recruitment Status : Recruiting
First Posted : December 19, 2019
Last Update Posted : January 27, 2020
Sponsor:
Collaborators:
United States Department of Defense
Office of Naval Research (ONR)
Information provided by (Responsible Party):
Steadman Philippon Research Institute

Brief Summary:
This is a prospective, randomized, placebo-controlled trial to evaluate potential beneficial effects of leukocyte-poor platelet rich plasma and bone marrow concentrate on the healing and health of critical joint tissues in the knee following anterior cruciate ligament (ACL) reconstruction. Bone marrow contains stem cells which can change into cells of various different tissue types, while platelet rich plasma contains growth factors. This trial will compare the two procedures against placebo.

Condition or disease Intervention/treatment Phase
Osteoarthritis, Knee Biological: Leukocyte-Poor Platelet Rich Plasma (LP-PRP) Biological: Bone Marrow Concentrate (BMC) Other: Control group (Placebo) Phase 1 Phase 2

Detailed Description:

This is a prospective, randomized, placebo-controlled trial. Patients will be randomized into three groups: Concentrated Bone Marrow Concentrate (BMC), Platelet-Rich Plasma (PRP) or Placebo. BMC subjects will have bone marrow aspirated from the subjects iliac crests and the cellular rich portion will be concentrated and subsequently injected into the subjects' symptomatic knee during ACL reconstruction surgery. PRP subjects will have a venous blood draw and the resulting PRP will be injected into the symptomatic knee during ACL reconstruction surgery. Follow-up visits involving imaging and biomotion testing will take place at 2 weeks, 6 months and 18 months after the ACL reconstruction surgery.

The purpose of this study is to evaluate potential beneficial effects of leukocyte-poor platelet-rich plasma (LP-PRP) and bone marrow concentrate (BMC) on the healing and health of all critical joint tissues (grafts/ligaments, meniscus and cartilage) in the knee following anterior cruciate ligament reconstruction (ACLR). Key aspects of this proposal include our well-developed methodologies to quantify and correlate cytokines, chemokines, growth factors in PRP and progenitor cells in BMC, clinical outcomes and imaging following ACLR. The overarching goal of this randomized control trial is to establish a biological signature of PRP and BMC that will be indicative for optimal recovery after ACLR. The long-term goal of our research is to better understand the efficacy of orthobiologic approaches to improve clinical outcomes, enhance graft healing and mitigate post-traumatic osteoarthritis (PTOA) in a cohort of patients that have undergone ACLR.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 99 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: Outcomes assessor
Primary Purpose: Treatment
Official Title: Prospective Evaluation of Platelet-Rich Plasma and Bone Marrow Concentrate Treatment to Accelerate Healing After Anterior Cruciate Ligament Reconstruction
Actual Study Start Date : January 2, 2020
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Leukocyte-Poor Platelet Rich Plasma (LP-PRP)
Participants will have a knee injected with Platelet-Rich Plasma (PRP) obtained from a venous whole blood draw from the vein.
Biological: Leukocyte-Poor Platelet Rich Plasma (LP-PRP)
Participants will have a knee injected with Platelet-Rich Plasma (PRP) obtained from a venous whole blood draw from the vein.

Experimental: Bone Marrow Concentrate (BMC)
Participants will have a knee injected with BMC stem cells harvested from the iliac crest
Biological: Bone Marrow Concentrate (BMC)
Participants will have a knee injected with BMC stem cells harvested from the iliac crest

Placebo Comparator: Control
Patients randomized in the placebo arm will undergo their standard of care treatment and will not receive LP-PRP or BMC.
Other: Control group (Placebo)
Participants will undergo ACLR surgery with no injection into their knee.




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 18 months ]
    Occurrence of adverse events


Secondary Outcome Measures :
  1. Patient reported outcome questionnaire [ Time Frame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery ]
    SF-12 Short Form General Health Survey Patient Satisfaction

  2. Measure signature cellular profile of BMC [ Time Frame: Day of Surgery ]
    Flow cytometer to analyze BMC cell concentrations

  3. Measure plasma levels of pro-inflammatory factors in BMC [ Time Frame: Day of Surgery ]
    Multiplex analysis of pro-inflammatory cytokines and chemokines using Luminex 200®

  4. Measure plasma levels of pro-inflammatory factors in LP-PRP [ Time Frame: Day of Surgery ]
    Multiplex analysis of pro-inflammatory cytokines and chemokines using Luminex 200®

  5. Quantitative Magnetic Resonance Imaging (MRI) [ Time Frame: screening, baseline; 6 and 18 months post-surgery ]
    Images acquired on a 3T Siemens Magnetom Skyra-fit scanner

  6. DSX: three dimensional (3D) to measure motion of the knee using dynamix x-ray software [ Time Frame: 6 and 18 months post-surgery ]
    Up to three brief X-ray exposures (5 frames at 100 frames/s, 0.05 s) will be acquired

  7. Computerized tomography (CT): 3D geometry of bony anatomy using a series of x-rays [ Time Frame: 6 months post-surgery ]
    single, bilateral knee CT scan using Toshiba Aquilon Premium 160 CT scanner

  8. Patient Reported Outcome questionnaire [ Time Frame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery ]
    IKDC - International Knee Documentation Committee Score

  9. Patient Reported Outcome questionnaire [ Time Frame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery ]
    WOMAC - Western Ontario & McMaster Universities Osteoarthritis Index

  10. Patient Reported Outcome questionnaire [ Time Frame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery ]
    Lysholm Score

  11. Patient Reported Outcome questionnaire [ Time Frame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery ]
    Tegner Activity Scale

  12. Patient Reported Outcome questionnaire [ Time Frame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery ]
    NRS (NUMERICAL RATING SCALE) for Pain

  13. Motion Assessment [ Time Frame: screening, baseline; 6 months post-surgery ]
    3D video motion capture



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria: Subjects will be included if all the following criteria are met:

  1. Age 16-50 years at the time of Anterior Cruciate Ligament Reconstruction (ACLR) surgery;
  2. Acute ACL injury within 6 months of scheduled ACLR surgery;
  3. Scheduled for unilateral, primary ACLR with a BTB (bone-patellar tendon-bone) autograft;
  4. The following concomitant injuries are allowed:

    1. Meniscal injuries of all types, grades and regardless of surgical treatment;
    2. Articular chondral injury that can be addressed with debridement or chondroplasty;
    3. Tibial impaction fractures;
    4. Non-operative sprains/injuries of MCL or LCL;
  5. Willing and able to comply with all required post-operative visits, biomotion and imaging tests, the self-completion of questionnaires and other trial procedures.

Exclusion Criteria: Subjects will be excluded if any of the following criteria are met:

  1. Inability to provide informed consent;
  2. Women who are pregnant;
  3. Previous surgery for either knee except in cases of prior diagnostic arthroscopy and/or minimal debridement;
  4. Significant osteoarthritis (OA) of the knee (e.g. grade 4 with cystic changes and/or significant osteophytes);
  5. Concomitant cartilage restoration procedure in the operative knee;
  6. Biologic treatment (e.g. PRP, BMC, prolotherapy, etc.) in the operative knee within 6 months of ACLR surgery;
  7. Steroid injections in the operative knee within 3 months of ACLR surgery;
  8. Open growth plates (determined by the treating physician based on standard-of-care preoperative knee radiographs);
  9. History of deep vein thrombosis (DVT) or pulmonary embolism (PE) that requires additional anticoagulation beyond usual post-operative standard of care;
  10. Current or known history of significant active autoimmune disease (i.e. rheumatoid arthritis and SLE);
  11. Incompatible MRI hardware/devices and/or inability to safely undergo MRI per the MRI safety screening questionnaire;
  12. Known balance or vestibular disorders, if in the opinion of the Principal Investigator or delegated clinician may affect ability to safely comply with study procedures;
  13. History of significant radiation exposure, e.g. due to radiation therapy or occupational exposure;
  14. Active malignancy of any type or history of a malignancy within 2 years of informed consent (with the exception of subjects with a history of treated basal or squamous cell carcinoma);
  15. Concurrent or previous participation in another clinical trial within 30 days prior to informed consent;

    1. Concurrent enrollment in DOD Project 4, Vail Health Hospital IRB # 2018-20, is allowed while subjects on this study are in the 18-month follow-up period;
    2. Concurrent enrollment in non-interventional registry studies or blood-banking/biomarker studies is allowed;
  16. History of substance abuse (drug or alcohol) that may interfere with the subject's ability to cooperate and comply with the trial procedures;
  17. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Principal Investigator or delegated clinician, would make the subject inappropriate for entry into this trial.

    Subjects will be withdrawn from the study (Screen Failures) after providing informed consent and/or at the time of ACLR surgery if they meet any of the following criteria:

  18. Concurrent reconstruction of any knee ligaments other than the ACL;
  19. ACLR which requires the following concomitant treatments: bone plating, metal implants (with the exception of titanium interference screws) or microfracture;
  20. Inability to collect sufficient research samples (e.g. less than the minimum required amount of BMA is harvested, or clotting occurs).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04205656


Contacts
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Contact: Holly del Junco 970-238-8086 hdeljunco@sprivail.org
Contact: Suzanne L Page, JD 970-401-8770 spage@sprivail.org

Locations
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United States, Colorado
The Steadman Clinic Recruiting
Vail, Colorado, United States, 81657
Contact: Holly del Junco    970-238-8086    hdeljunco@sprivail.org   
Contact: Suzanne L Page, JD    970-401-8770    spage@sprivail.org   
Principal Investigator: Peter Millett, MD         
Sub-Investigator: Matthew Provencher, MD         
Sub-Investigator: Thomas Hackett, MD         
Sub-Investigator: Leslie Vidal, MD         
Sub-Investigator: Armando Vidal, MD         
Sub-Investigator: Jon Godin, MD         
Sub-Investigator: Thomas Evans, MD         
Sponsors and Collaborators
Steadman Philippon Research Institute
United States Department of Defense
Office of Naval Research (ONR)
Investigators
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Principal Investigator: Peter Millett, MD The Steadman Clinic
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Responsible Party: Steadman Philippon Research Institute
ClinicalTrials.gov Identifier: NCT04205656    
Other Study ID Numbers: 2019-13
First Posted: December 19, 2019    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Steadman Philippon Research Institute:
bone marrow concentrate (BMC)
stem cell
platelet-rich plasma (PRP)
anterior cruciate ligament reconstruction (ACLR)
Additional relevant MeSH terms:
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Osteoarthritis, Knee
Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases