Freeze-dried Bovine Hydroxyapatite/Secretome Composite for Bone Defects

Clinical Trial of Freeze-dried Bovine Hydroxyapatite/Secretome Composite Application for the Management of Long Bone Defects in the Lower Extremities

This clinical trial aims to investigate the efficacy of freeze-dried bovine hydroxyapatite/secretome composite application for the management of long bone defects and other bone healing disorders in the lower extremities.

Study Overview

• Status: Recruiting
• Conditions: Bone Loss
• Intervention / Treatment: Procedure: ORIF + autograft; Procedure: ORIF + FD BHA/Secretome

Detailed Description

The gold standard for treating bone defect conditions is autologous bone graft (autograft). Autograft promotes bone healing due to its osteoconductive (serving as a foundation that facilitates bone growth), osteoinductive (stimulates progenitor cells), and osteogenesis (acting as a precursor of osteoblasts and osteoclasts) properties. However, donor site morbidity and persisting pain following harvest remains a major problem. Hence, we attempt to investigate the efficacy of other bone substitutes, i.e., bovine hydroxyapatite/secretome composite, to treat long bone defects and other bone healing disorders in the lower extremities.

Bovine hydroxyapatite (BHA) is a xenograft (animal-derived graft) with osteoconductive properties. Simultaneously, the secretome of the mesenchymal stem cells contains cytokines, chemokines, and growth factors, which possess osteoinductive properties. Thus, we hypothesize that the combination (composite) of BHA/secretome (in the form of freeze-dried (FD) BHA/secretome composite) will promote bone healing ability that is equal to autografts while eliminating donor-site morbidity in the patient.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ferdiansyah Mahyudin, MD, Ph.D; Phone Number: +62811320635; Email: ferdyortho@yahoo.com

Study Locations

• Indonesia
  • East Java
    • Surabaya, East Java, Indonesia, 60286
      • Recruiting
      • Dr. Soetomo General Hospital
      • Contact: Ferdiansyah Mahyudin, MD, Ph.D; Phone Number: 0811320635; Email: ferdyortho@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients presenting with bone defects (less than 5 cm) in the diaphysis of the long bones of the lower extremities due to trauma and other bone healing disorders
• No history of comorbid diseases
• Willing to be involved in the clinical trial

Exclusion Criteria:

• Patients with bone defects or impaired bone healing caused by tumors, infections, and metabolic diseases
• Suffered from multiple fractures and multitrauma patients
• Loss to follow-up

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group (ORIF + autograft); The patients will receive the current gold standard to treat long bone defects.	Procedure: ORIF + autograft; Patients will undergo a standard open reduction internal fixation (ORIF) procedure with autograft implantation (from the iliac crest).
Experimental: Treatment Group (ORIF + FD BHA/Secretome composite); The patients will receive a novel bone substitute following the ORIF procedure.	Procedure: ORIF + FD BHA/Secretome; Patients will undergo an ORIF procedure and subsequently receive freeze-dried bovine hydroxyapatite/secretome composite implantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
X-ray evaluation immediately following surgery.	A two-view (anterior-posterior/AP and lateral) radiograph will be taken immediately following surgery. The x-ray evaluation will be carried out by a blinded outcome assessor using a scoring system named Radiographic Union Score (Whelan et al., 2010) to assess bone union based on fracture line, callus, and graft resorption on plain radiograph after fracture. This score ranges from 4 to 12, with a higher score indicating a more favorable outcome (better bone healing).	Day-0
X-ray evaluation at 4 weeks following surgery	A two-view (anterior-posterior/AP and lateral) radiograph will be taken immediately following surgery. The x-ray evaluation will be carried out by a blinded outcome assessor using a scoring system named Radiographic Union Score (Whelan et al., 2010) to assess bone union based on fracture line, callus, and graft resorption on plain radiograph after fracture. This score ranges from 4 to 12, with a higher score indicating a more favorable outcome (better bone healing).	4 weeks
X-ray evaluation at 8 weeks following surgery.	A two-view (anterior-posterior/AP and lateral) radiograph will be taken immediately following surgery. The x-ray evaluation will be carried out by a blinded outcome assessor using a scoring system named Radiographic Union Score (Whelan et al., 2010) to assess bone union based on fracture line, callus, and graft resorption on plain radiograph after fracture. This score ranges from 4 to 12, with a higher score indicating a more favorable outcome (better bone healing).	8 weeks
X-ray evaluation at 12 weeks following surgery.	A two-view (anterior-posterior/AP and lateral) radiograph will be taken immediately following surgery. The x-ray evaluation will be carried out by a blinded outcome assessor using a scoring system named Radiographic Union Score (Whelan et al., 2010) to assess bone union based on fracture line, callus, and graft resorption on plain radiograph after fracture. This score ranges from 4 to 12, with a higher score indicating a more favorable outcome (better bone healing).	12 weeks
X-ray evaluation at 16 weeks following surgery.	A two-view (anterior-posterior/AP and lateral) radiograph will be taken immediately following surgery. The x-ray evaluation will be carried out by a blinded outcome assessor using a scoring system named Radiographic Union Score (Whelan et al., 2010) to assess bone union based on fracture line, callus, and graft resorption on plain radiograph after fracture. This score ranges from 4 to 12, with a higher score indicating a more favorable outcome (better bone healing).	16 weeks
Ultrasonography evaluation at 2 weeks	A blinded outcome assessor will perform ultrasonography (USG) evaluation to assess the four stages of the bone healing process using a scoring system named Sonographic Union Score developed by our institution. We will evaluate the following parameters: (1) hematoma organization, (2) neovascularization, (3) bone fracture tip echogenicity, (4) bone fracture border, (5) bridging callus echogenicity, (6) bone to bone graft junction gap, (7) callus formation mineralization, (8) bone surface continuity.	2 weeks
Ultrasonography evaluation at 4 weeks	A blinded outcome assessor will perform ultrasonography (USG) evaluation to assess the four stages of the bone healing process using a scoring system named Sonographic Union Score developed by our institution. We will evaluate the following parameters: (1) hematoma organization, (2) neovascularization, (3) bone fracture tip echogenicity, (4) bone fracture border, (5) bridging callus echogenicity, (6) bone to bone graft junction gap, (7) callus formation mineralization, (8) bone surface continuity.	4 weeks
Ultrasonography evaluation at 8 weeks	A blinded outcome assessor will perform ultrasonography (USG) evaluation to assess the four stages of the bone healing process using a scoring system named Sonographic Union Score developed by our institution. We will evaluate the following parameters: (1) hematoma organization, (2) neovascularization, (3) bone fracture tip echogenicity, (4) bone fracture border, (5) bridging callus echogenicity, (6) bone to bone graft junction gap, (7) callus formation mineralization, (8) bone surface continuity.	8 weeks
Ultrasonography evaluation at 12 weeks	A blinded outcome assessor will perform ultrasonography (USG) evaluation to assess the four stages of the bone healing process using a scoring system named Sonographic Union Score developed by our institution. We will evaluate the following parameters: (1) hematoma organization, (2) neovascularization, (3) bone fracture tip echogenicity, (4) bone fracture border, (5) bridging callus echogenicity, (6) bone to bone graft junction gap, (7) callus formation mineralization, (8) bone surface continuity.	12 weeks
Ultrasonography evaluation at 16 weeks	A blinded outcome assessor will perform ultrasonography (USG) evaluation to assess the four stages of the bone healing process using a scoring system named Sonographic Union Score developed by our institution. We will evaluate the following parameters: (1) hematoma organization, (2) neovascularization, (3) bone fracture tip echogenicity, (4) bone fracture border, (5) bridging callus echogenicity, (6) bone to bone graft junction gap, (7) callus formation mineralization, (8) bone surface continuity.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional evaluation at 8 weeks following surgery.	The functional evaluation will be assessed by using a scoring system named LEFS (Lower Extremity Functional Scale). LEFS is a widely known and validated patient-reported outcome measures (PROM) comprising 20 questions that is used to assess lower extremity functions. The patients will be asked to rate the activity listed from 0 to 4 (0 refers to an extreme difficulty/unable to perform activity, while 4 refers to having no difficulty at all). A higher score (maximum 80 points) indicates a very high function (i.e., a more favorable outcome).	8 weeks
Functional evaluation at 12 weeks following surgery.	The functional evaluation will be assessed by using a scoring system named LEFS (Lower Extremity Functional Scale). LEFS is a widely known and validated patient-reported outcome measures (PROM) comprising 20 questions that is used to assess lower extremity functions. The patients will be asked to rate the activity listed from 0 to 4 (0 refers to an extreme difficulty/unable to perform activity, while 4 refers to having no difficulty at all). A higher score (maximum 80 points) indicates a very high function (i.e., a more favorable outcome).	12 weeks
Functional evaluation at 16 weeks following surgery.	The functional evaluation will be assessed by using a scoring system named LEFS (Lower Extremity Functional Scale). LEFS is a widely known and validated patient-reported outcome measures (PROM) comprising 20 questions that is used to assess lower extremity functions. The patients will be asked to rate the activity listed from 0 to 4 (0 refers to an extreme difficulty/unable to perform activity, while 4 refers to having no difficulty at all). A higher score (maximum 80 points) indicates a very high function (i.e., a more favorable outcome).	16 weeks

Collaborators and Investigators

• Sponsor: Dr. Soetomo General Hospital
• Collaborators: Dr. Ramelan Naval Hospital; Airlangga University Hospital; Sidoarjo General Hospital; Cell & Tissue Bank, Dr. Soetomo General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: July 18, 2021
• First Submitted That Met QC Criteria: July 18, 2021
• First Posted (Actual): July 28, 2021

Study Record Updates

• Last Update Posted (Actual): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 18, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Mesenchymal Stem Cells; Secretome; Bone Substitutes; Bone Defects; Hydroxyapatites
• Other Study ID Numbers: 0045/KEPK/VIII/2020

Drug and device information, study documents

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