Utilization of Autologous Mesenchymal Cells in Posterolateral Spinal Fusion in Degenerative Spine Disease (AMSC-DSD-001)
Primary Purpose
Degenerative Disc Disease
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Suspension of human autologous MSC 3P in 1.5 ml
Sponsored by
About this trial
This is an interventional treatment trial for Degenerative Disc Disease
Eligibility Criteria
Inclusion Criteria:
- established diagnosis of spinal degenerative disease indicated for lumbar spine surgery,
- patients indicated for fusion therapy,
- patients between 18-55 years, both sexes,
- patients able to provide written informed consent.
Exclusion Criteria:
- previous lumbar spine surgery in the same segment of the spine, in order to achieve vertebral fusion,
- osteoporosis,
- diabetes mellitus,
- pregnancy or breastfeeding,
- women of childbearing potential not using effective contraception (established oral contraception, intrauterine device, ligation of the uterine tube) including proven contraceptive measures taken by their sexual partners,
- fertile men not using proven contraceptive measures including effective contraception method in their partner (established oral contraception, intrauterine device, ligation of the uterine tube),
- coagulopathy,
- malnutrition, primary biliary cirrhosis,
- skin infection at the site of bone marrow aspiration or at the site of spinal fusion,
- gastrostomy,
- any significant medical condition that would compromise the safety of the patient (e.g. recent myocardial infarction, congestive heart failure, renal failure, liver failure, systemic infection, recurrent thromboembolic disease .....),
- alcohol or drug abuse,
- cancer (compulsory clinical oncological screening),
- ongoing or recent (last 3 months) systemic corticosteroid or immunosuppressive therapy.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Human AMSC (passage 3) 3P in 1.5 mL
Arm Description
Patient receiving the investigational medicinal product - suspension of human autologous MSC 3P in 1.5 mL
Outcomes
Primary Outcome Measures
Safety: To demonstrate absence of complications at the site of spinal fusion
Complications at the site of spinal fusion and other treatment-related adverse events will be recorded in ten patients at Visits I through VII. All adverse events (AEs) will be classified by seriousness, severity and relationship to hAMSC application.
All AEs will be collected as symptoms spontaneously reported by the patient, clinically relevant changes and abnormalities observed by the Investigator (clinically significant laboratory measurements confirmed by repeated measurement, results of physical examinations) Intensity
The following 3-point rating scale will be used for rating of the intensity of each AE:
Mild: Awareness of signs or symptoms, but no disruption of usual activity Moderate: Event sufficient to affect usual activities (disturbing) Severe: Inability to work or perform usual activities (unacceptable)
Secondary Outcome Measures
Efficacy: To assess the quality of life determined by Oswestry Questionnaire.
The quality of life determined by Oswestry Questionnaire will be recorded in ten patients at Visits II, and IV through VII. The test has 10 sections and maximum score is 50 points; change from the baseline valie will be recorded. The points are then transferred into percentage and interpreted in a standard way when 0-20% means minimal disability while 81-100% means bed-bound condition. Minimum detectable change (90 % confidence) is 10 % (5 points).
Efficacy: To assess the quality of spinal fusion by X-ray imaging
The quality of spinal fusion will be measured by X-ray imaging at Visits V and VII. Dynamic X-ray of the lumbar spine will be performed at 3 and 12 months following the surgery and hAMSC application to measure the angle of the spine movement in the fusion area. The angle will be recorded in degrees. The movements above 10 degrees will beregarded as "unstable".
The bone fusion morphology will be evaluated based on the following scale:
Cyst or pseudo-cyst formation
Fusion not visible
Pseudo-joint (or false joint) development
Low degree of bone fusion
High degree of bone fusion
Efficacy: To assess the quality of spinal fusion measured by computed tomography (CT).
The quality of spinal fusion will be measured by CT in ten patients at Visits V and VII.
The density will of the fusion will be expressed as % on a linear scale between two standardized measuring points: soft tissue= 0%, vertebral arch= 100%.
Full Information
NCT ID
NCT03827096
First Posted
January 14, 2019
Last Updated
January 14, 2020
Sponsor
Bioinova, s.r.o.
Collaborators
Department of Spine Surgery, University Hospital Motol, Prague, Czech Republilc
1. Study Identification
Unique Protocol Identification Number
NCT03827096
Brief Title
Utilization of Autologous Mesenchymal Cells in Posterolateral Spinal Fusion in Degenerative Spine Disease
Acronym
AMSC-DSD-001
Official Title
Utilization of Autologous Mesenchymal Cells in Posterolateral Spinal Fusion in Degenerative Spine Disease to Assess the Safety and the Efficacy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Why Stopped
Primary endpoint (Safety) has been achieved
Study Start Date
August 27, 2013 (Actual)
Primary Completion Date
December 14, 2016 (Actual)
Study Completion Date
December 14, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bioinova, s.r.o.
Collaborators
Department of Spine Surgery, University Hospital Motol, Prague, Czech Republilc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Subjects in whom a posterolateral fusion surgery has been planned and who meet the inclusion and exclusion criteria were proposed to receive a single-dose AMSC treatment, in order to assess its safety and efficacy on posterolateral interbody fusion. After the surgery, the subjects were followed up as out-patients during 5 study visits for 12 months in total.
Detailed Description
Following informed consent collection at the screening visit and verification of all inclusion and exclusion criteria, eligible patients will undergo the procedure of bone marrow cell aspiration from iliac crest for the purpose of receiving autologous multipotent mesenchymal stem cells. The cells will be cultivated for 3 passages (for 3 - 4 weeks) in order to expand them to sufficient quantity. Suspension of the cultured AMSC will then be sterilely packed and transported to the surgery site. During the posterolateral spine fusion operation, 1.5 ml of cell suspension will be mixed with 5 cc of beta-tricalcium phosphate foam (Vitoss™, Orthovita) and 3.5 ml of patient's blood, and inserted between the transverse processes of the lumbar spine.
All subjects will be hospitalized and followed up as per standard medical care rules used in the investigational site hospital for this type of intervention.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Degenerative Disc Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Human AMSC (passage 3) 3P in 1.5 mL
Arm Type
Experimental
Arm Description
Patient receiving the investigational medicinal product - suspension of human autologous MSC 3P in 1.5 mL
Intervention Type
Drug
Intervention Name(s)
Suspension of human autologous MSC 3P in 1.5 ml
Other Intervention Name(s)
hAMSC
Intervention Description
During the posterolateral spine fusion operation, 1.5 ml of cell suspension was mixed with 5cc of beta-tricalcium phosphate foam and 3.5 ml of patient's blood, and inserted between the right transverse processes of the lumbar spine.
Primary Outcome Measure Information:
Title
Safety: To demonstrate absence of complications at the site of spinal fusion
Description
Complications at the site of spinal fusion and other treatment-related adverse events will be recorded in ten patients at Visits I through VII. All adverse events (AEs) will be classified by seriousness, severity and relationship to hAMSC application.
All AEs will be collected as symptoms spontaneously reported by the patient, clinically relevant changes and abnormalities observed by the Investigator (clinically significant laboratory measurements confirmed by repeated measurement, results of physical examinations) Intensity
The following 3-point rating scale will be used for rating of the intensity of each AE:
Mild: Awareness of signs or symptoms, but no disruption of usual activity Moderate: Event sufficient to affect usual activities (disturbing) Severe: Inability to work or perform usual activities (unacceptable)
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Efficacy: To assess the quality of life determined by Oswestry Questionnaire.
Description
The quality of life determined by Oswestry Questionnaire will be recorded in ten patients at Visits II, and IV through VII. The test has 10 sections and maximum score is 50 points; change from the baseline valie will be recorded. The points are then transferred into percentage and interpreted in a standard way when 0-20% means minimal disability while 81-100% means bed-bound condition. Minimum detectable change (90 % confidence) is 10 % (5 points).
Time Frame
1 year
Title
Efficacy: To assess the quality of spinal fusion by X-ray imaging
Description
The quality of spinal fusion will be measured by X-ray imaging at Visits V and VII. Dynamic X-ray of the lumbar spine will be performed at 3 and 12 months following the surgery and hAMSC application to measure the angle of the spine movement in the fusion area. The angle will be recorded in degrees. The movements above 10 degrees will beregarded as "unstable".
The bone fusion morphology will be evaluated based on the following scale:
Cyst or pseudo-cyst formation
Fusion not visible
Pseudo-joint (or false joint) development
Low degree of bone fusion
High degree of bone fusion
Time Frame
1 year
Title
Efficacy: To assess the quality of spinal fusion measured by computed tomography (CT).
Description
The quality of spinal fusion will be measured by CT in ten patients at Visits V and VII.
The density will of the fusion will be expressed as % on a linear scale between two standardized measuring points: soft tissue= 0%, vertebral arch= 100%.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
established diagnosis of spinal degenerative disease indicated for lumbar spine surgery,
patients indicated for fusion therapy,
patients between 18-55 years, both sexes,
patients able to provide written informed consent.
Exclusion Criteria:
previous lumbar spine surgery in the same segment of the spine, in order to achieve vertebral fusion,
osteoporosis,
diabetes mellitus,
pregnancy or breastfeeding,
women of childbearing potential not using effective contraception (established oral contraception, intrauterine device, ligation of the uterine tube) including proven contraceptive measures taken by their sexual partners,
fertile men not using proven contraceptive measures including effective contraception method in their partner (established oral contraception, intrauterine device, ligation of the uterine tube),
coagulopathy,
malnutrition, primary biliary cirrhosis,
skin infection at the site of bone marrow aspiration or at the site of spinal fusion,
gastrostomy,
any significant medical condition that would compromise the safety of the patient (e.g. recent myocardial infarction, congestive heart failure, renal failure, liver failure, systemic infection, recurrent thromboembolic disease .....),
alcohol or drug abuse,
cancer (compulsory clinical oncological screening),
ongoing or recent (last 3 months) systemic corticosteroid or immunosuppressive therapy.
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
The data will be published
Learn more about this trial
Utilization of Autologous Mesenchymal Cells in Posterolateral Spinal Fusion in Degenerative Spine Disease
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