Effect of PRP Versus BMC in Anterior Cruciate Ligament Reconstruction

The Therapeutic Effect of Autologous Platelet-Rich Plasma Versus Bone Marrow Concentrate in Anterior Cruciate Ligament Reconstruction - A Prospective, Double-Blind Randomized Controlled Study

Anterior cruciate ligament (ACL) is an important stabilizer of knee during daily activity and exercise. The ruptured ACL need to be reconstructed by a new tendon graft which passed the bone tunnel and joint during operation. How to enhance the tendon graft to bone tunnel healing is critical important to prevent recurrent ligament laxity, avoid secondary osteoarthritis, and achieve early return to sports and work.

Platelet Rich Plasma (PRP)，harvest from peripheral blood, is rich in multiple growth factors(i.e. VEGF, PDGD, TGFB, IGF, EGF) which help the injured tissue regeneration. Bone marrow stem cell has been demonstrated to enhance the injured tissue repair both in vitro and in vivo study.

However, there is no prospective study in comparing the PRP and BMC to enhance interfacial healing between graft and bone tunnel in ACL reconstruction. Investigators hypothesize that the combination of PRP and BMC has synergetic effect in interfacial healing in ACL reconstruction.

Aim of this study： To investigate the result of clinical functional scoring, MRI, and biomechanical study between PRP augmentation, PRP+BMC augmentation and traditional ACL reconstruction.

Study Overview

• Status: Completed
• Conditions: Anterior Cruciate Ligament Reconstruction
• Intervention / Treatment: Combination product: Platelet-Rich Plasma; Bone marrow concentrate

Detailed Description

Anterior cruciate ligament (ACL) is an important stabilizer of knee during daily activity and exercise. According to literature, there are 100,000- 200,000 ACL tear case annually in US. The patients with ACL tear will sustain with joint pain, muscle weakness, giving way sensation, other knee ligaments or meniscus injury, and consequent osteoarthritis change. However, the ruptured ACL cannot heal by itself due to limited vascularity supply, intraarticular inflammatory factors which inhibit the ACL cells migration and proliferation. The ruptured ACL need to be reconstructed by a new tendon graft which passed the bone tunnel and joint during operation. How to enhance the tendon graft to bone tunnel healing is critical important to prevent recurrent ligament laxity, avoid secondary osteoarthritis, and achieve early return to sports and work.

Platelet Rich Plasma (PRP)，harvest from peripheral blood, is rich in multiple growth factors(i.e. VEGF, PDGD, TGFB, IGF, EGF) which help the injured tissue regeneration. The PRP has been applied in treating tendinitis, osteoarthritis, cartilage injury, and bone nonunion. Bone marrow contains lots of stem cell and progenitor cells with capability of self-renewal and multi-differentiation. Bone marrow stem cell has been demonstrated to enhance the injured tissue repair both in vitro and in vivo study. The bone marrow concentrate (BMC) can be isolated from the bone marrow through the centrifuge procedure at one time which contains multiple stem cells. The bone marrow can regenerate itself around 1 week.

In recent years, many authors uses the combination of RPP and BMC to treat injured tissue. However, there is no prospective study in comparing the PRP and BMC to enhance interfacial healing between graft and bone tunnel in ACL reconstruction. Investigators hypothesize that the combination of PRP and BMC has synergetic effect in interfacial healing in ACL reconstruction.

The purpose of this study is to investigate the clinical outcome of autologous PRP, and combined BMC+PRP in tendon graft augmentation in the ACL reconstruction surgery with functional score and MRI evaluation. Investigators will analyze the therapeutic effect using one-way ANOVA. To investigate the result of clinical functional scoring, MRI, and biomechanical study between PRP augmentation, PRP+BMC augmentation and traditional ACL reconstruction.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≧ 20 year-old
• the patient has been confirmed ACL rupture and the reconstruction is indicated
• sign IRB and operation consent

Exclusion Criteria:

• combined other ligament or extremities injury
• prior the same knee surgery
• open wound or operation history at knee joint
• Severe knee osteoarthritis
• history of multiple joint arthritis or rheumatoid arthritis
• Systemic diseases (infections, malignancies, immunodepression)
• patients with bleeding tendency, anticoagulant or antiaggregant therapies
• patients with Hb values < 11 g/dl and/or platelet values < 150,000/mm
• refuse to sign Informed Consent Form and operation consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PRP augmentation ACL reconstruction group; Platelet-rich plasma (PRP) (Dosage form: APA-15)	Combination product: Platelet-Rich Plasma; Bone marrow concentrate; Platelet-rich plasma (PRP) (Dosage form: APA-15) Bone marrow concentrate (BMC) (Dosage form: APA-15Q)
Experimental: PRP+BMC augmentation ACL reconstruction group; Bone marrow concentrate (BMC) (Dosage form: APA-15Q)	Combination product: Platelet-Rich Plasma; Bone marrow concentrate; Platelet-rich plasma (PRP) (Dosage form: APA-15) Bone marrow concentrate (BMC) (Dosage form: APA-15Q)
No Intervention: Traditional ACL reconstruction group; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
X-ray	X-ray to evaluate the joint space, graft to bone healing status and graft incorporation.	preoperative
X-ray	X-ray to evaluate the joint space, graft to bone healing status and graft incorporation.	3 months after ACL reconstruction.
X-ray	X-ray to evaluate the joint space, graft to bone healing status and graft incorporation.	6 months after ACL reconstruction.
X-ray	X-ray to evaluate the joint space, graft to bone healing status and graft incorporation.	12 months after ACL reconstruction.
MRI	MRI to evaluate the joint space, graft to bone healing status and graft incorporation.	preoperative
MRI of operated knee	MRI to evaluate the joint space, graft to bone healing status and graft incorporation.	3 months after ACL reconstruction.
MRI of operated knee	MRI to evaluate the joint space, graft to bone healing status and graft incorporation.	6 months after ACL reconstruction.
MRI of operated knee	MRI to evaluate the joint space, graft to bone healing status and graft incorporation.	12 months after ACL reconstruction.
Lysholm score	Lysholm score to evaluate the knee function recovery	preoperative
Lysholm score	Lysholm score to evaluate the knee function recovery	3 months after ACL reconstruction.
Lysholm score	Lysholm score to evaluate the knee function recovery	6 months after ACL reconstruction.
Lysholm score	Lysholm score to evaluate the knee function recovery	12 months after ACL reconstruction.
IKDC 2000	IKDC 2000 to evaluate the knee function recovery	preoperative
IKDC 2000	IKDC 2000 to evaluate the knee function recovery	3 months after ACL reconstruction.
IKDC 2000	IKDC 2000 to evaluate the knee function recovery	6 months after ACL reconstruction.
IKDC 2000	IKDC 2000 to evaluate the knee function recovery	12 months after ACL reconstruction.
Muscle power (N.m/kg)	muscle power test by Biodex System 3 Pro	preoperative
Muscle power (N.m/kg)	muscle power test by Biodex System 3 Pro	3 months after ACL reconstruction.
Muscle power (N.m/kg)	muscle power test by Biodex System 3 Pro	6 months after ACL reconstruction.
Muscle power (N.m/kg)	muscle power test by Biodex System 3 Pro	12 months after ACL reconstruction.
Proprioception (degree)	Proprioception test by Biodex System 3 Pro	preoperative
Proprioception (degree)	Proprioception test by Biodex System 3 Pro	3 months after ACL reconstruction.
Proprioception (degree)	Proprioception test by Biodex System 3 Pro	6 months after ACL reconstruction.
Proprioception (degree)	Proprioception test by Biodex System 3 Pro	12 months after ACL reconstruction.

Collaborators and Investigators

• Sponsor: Kaohsiung Medical University Chung-Ho Memorial Hospital
• Collaborators: Ministry of Health and Welfare, Taiwan
• Investigators: Principal Investigator: Pei-Hsi Chou, PhD, Kaohsiung Medical University Chung-Ho Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2018
• Primary Completion (Actual): July 4, 2020
• Study Completion (Actual): July 4, 2020

Study Registration Dates

• First Submitted: September 30, 2021
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (Actual): January 13, 2022

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: January 3, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Anterior cruciate ligament reconstruction; Platelet-Rich Plasma; Bone marrow concentrate; Hamstring tendon
• Other Study ID Numbers: KMUHIRB-F(I)-20170122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is not a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No