Clinical trial NCT04205656: Prospective Evaluation of PRP and BMC Treatment to Accelerate Healing After ACL Reconstruction
Official title: Prospective Evaluation of Platelet-Rich Plasma and Bone Marrow Concentrate Treatment to Accelerate Healing After Anterior Cruciate Ligament Reconstruction
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Osteoarthritis, Knee
Keywords: bone marrow concentrate (BMC)
stem cell
platelet-rich plasma (PRP)
anterior cruciate ligament reconstruction (ACLR)
Lead sponsor: Steadman Philippon Research Institute
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
name: Office of Naval Research (ONR)
First posted: 2019-12-19
Enrollment: 45
Sex: ALL
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 in person will take place at 2 weeks, 6 months and 12 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.

Eligibility 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).

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: 18 months
Secondary outcomes:
measure: Patient reported outcome questionnaire
timeFrame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery
measure: Measure signature cellular profile of BMC
timeFrame: Day of Surgery
measure: Measure plasma levels of pro-inflammatory factors in BMC
timeFrame: Day of Surgery
measure: Measure plasma levels of pro-inflammatory factors in LP-PRP
timeFrame: Day of Surgery
measure: Quantitative Magnetic Resonance Imaging (MRI)
timeFrame: screening, baseline; 6 and 12 months post-surgery
measure: DSX: three dimensional (3D) to measure motion of the knee using dynamix x-ray software
timeFrame: 6 and 12 months post-surgery
measure: Computerized tomography (CT): 3D geometry of bony anatomy using a series of x-rays
timeFrame: 6 months post-surgery
measure: Patient Reported Outcome questionnaire
timeFrame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery
measure: Patient Reported Outcome questionnaire
timeFrame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery
measure: Patient Reported Outcome questionnaire
timeFrame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery
measure: Patient Reported Outcome questionnaire
timeFrame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery
measure: Patient Reported Outcome questionnaire
timeFrame: screening, baseline, two weeks post-surgery, then every week for 8 weeks post-surgery; 3, 6 12 and 18 months post-surgery
measure: Motion Assessment
timeFrame: screening, baseline; 6 months post-surgery
Other outcomes:
Locations:
city: Vail
country: United States
facility: 181 West Meadow Drive, Suite 1000
state: Colorado
Study officials:
affiliation: The Steadman Clinic
name: Peter Millett, MD
role: PRINCIPAL_INVESTIGATOR
References: