Protocol summary
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Study aim
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Safety & efficacy evaluation of intra-articular transplantation of 3 consecutive doses of allogenic umbilical cord tissue-derived stromal mesenchymal cells in patients with knee osteoarthritis
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Design
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Randomised controlled trial, with parallel groups, double-blind, phase 1/2 on 30 patients, randomized using Random allocation software
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Settings and conduct
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Patients are transplanted 3 times at intervals of 0, 2 and 4 months in the operating room of Royan Clinic. Patients will be monitored for up to one year.
For the purpose of blinding, the biological product will be prepared in the form of disposable 5 cc syringes that look exactly like each other with a special label. Only the doctor and the person in charge of the transplant will know the type of treatment received.
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Participants/Inclusion and exclusion criteria
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- Inclusion criteria:
Age 40-70 years
Knee osteoarthritis with grades 2 and 3
Diagnosis by radiograph of standing knee
VAS Knee pain: ≥4
Complete the informed consent form
- Exclusion criteria:
Knee deviation more than 15 degrees
BMI ≥ 35
Pregnant women, nursing mothers or adults with disabilities
Intra-cartilage injection during the last 2 months
Arthroscopy in the last 6 months
Abnormal hematological or biochemical tests
Any type of neoplasm
Take aspirin 1 week before the cell injection
Coagulopathy or use of anticoagulants
Positive viral tests
Rheumatoid arthritis or other autoimmune diseases involving the joints
Allergy to substances in the culture medium
Corticosteroid use in 3 months
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Intervention groups
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Control group: 3 doses of normal saline + hyaluronic acid
Test Group: 3 doses of normal saline containing mesenchymal cells derived from non-native umbilical cord tissue + hyaluronic acid
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Main outcome variables
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Adverse events (AEs) and severe adverse events (SAEs)
WOMAC
VAS
SF-36
Articular cartilage thickness
General information
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Reason for update
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Add information about the new sponsor (Cell-Tech Pharmed) of this clinical trial
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20211102052944N1
Registration date:
2021-11-09, 1400/08/18
Registration timing:
prospective
Last update:
2021-11-27, 1400/09/06
Update count:
1
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Registration date
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2021-11-09, 1400/08/18
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2021-11-22, 1400/09/01
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Expected recruitment end date
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2022-05-22, 1401/03/01
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Evaluation of safety and efficacy of intra-articular knee transplantation of three consecutive doses of allogenic umbilical cord mesenchymal stromal cells in patients with knee osteoarthritis: interventional clinical trial, phase I/II
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Public title
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Intra-articular transplantation of umbilical cord stromal mesenchymal cells in patients with knee osteoarthritis
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
40-70 years
Unilateral knee osteoarthritis
Kellgren and Lawrence grade of both knees between 2 and 3
Evidence of x-ray imaging findings compatible with knee osteoarthritis
knee pain for at least 4 months that has not responded to common medical and physical therapies.
Visual analogue score ≥ 4
Informed consent
Exclusion criteria:
Pregnancy or lactation
Inflammatory or infectious arthritis
Intra-articular injection during the last 2 months
Body Mass Index ≥ 35
Haematological and biochemical analysis with significant alterations that contraindicates intervention
Known and uncontrolled chronic disease (including diabetes (HbA1c ≥ 8), heart failure (EF <45%), renal failure (Cr> 2), liver failure (AST, ALT> 100)
History of any type of neoplasm
Take aspirin one week before the cell injection
History of coagulopathy or use of anticoagulants
Positive viral tests (HIV, CMV, HTLV1 & 2, HBV, HCV)
Having a movement disorder
Having serious illnesses with a life expectancy of less than 1 year
Drug or alcohol abuse
History or clinical diagnosis of any psychological disorder
Arthroscopy in the last 6 months
Rheumatoid arthritis or other autoimmune diseases that affect the joints.
Immunosuppression or taking systemic immunosuppressant
Allergy to proteins or substances in culture medium (gentamicin, bovine or equine serum)
History of corticosteroid use 3 months before enrolment
Knee joint misalignment ≥15 degree
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Age
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From 40 years old to 70 years old
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Gender
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Both
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Phase
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1-2
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Groups that have been masked
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- Participant
- Investigator
- Outcome assessor
- Data analyser
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Sample size
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Target sample size:
30
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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Patients will be randomly assigned to the control and MSC groups. The method of random assignment of these two groups is block randomization. The size of the blocks is 6 people and using Random allocation software, the sequence of assigning patients to the groups is determined, and this sequence will be kept by the transplant manager.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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This study is a double-blind study. Patients and study analysts will be unaware of the type of treatment assigned. To achieve this goal, by using a biological product in the form of disposable 5 cc syringes that are already filled by the nurse and are completely "similar" to the type of treatment received, to blind the participants in the study. Also, the people who apply the treatment will be different from the people who are responsible for examining and evaluating the patients, and the biological product packages will be labeled according to a specific code. Only the doctor and the person in charge of the transplant will know the type of treatment the patients receive.
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Placebo
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Not used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2021-09-21, 1400/06/30
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Ethics committee reference number
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IR.ACECR.ROYAN.REC.1400.079
Health conditions studied
1
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Description of health condition studied
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Knee Osteoarthritis
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ICD-10 code
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M17
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ICD-10 code description
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Osteoarthritis of knee
Primary outcomes
1
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Description
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Adverse events and severe adverse events
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Timepoint
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2, 4, 6, 9, and 12 months after intervention
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Method of measurement
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Clinical signs and questionnaire
Secondary outcomes
1
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Description
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Visual analog scale
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Timepoint
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Baseline and 2, 4, 6, 9, and 12 months after intervention
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Method of measurement
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Visual Analogue Scale Questionnaire
2
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Description
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Western Ontario and McMaster Universities Osteoarthritis Index
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Timepoint
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Baseline and 2, 4, 6, 9, and 12 months after intervention
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Method of measurement
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ٌWOMAC Questionnaire
3
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Description
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Disability index
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Timepoint
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Baseline and 6, 9, and 12 months after intervention
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Method of measurement
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Short Form Health-36 Questionnaire
4
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Description
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Articular cartilage thickness
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Timepoint
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Baseline and 6, 9, and 12 months after intervention
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Method of measurement
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Magnetic resonance imaging
Intervention groups
1
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Description
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Control group: Patients receiving 3 doses of normal saline + Hyaluronic acid The procedure will be performed in such a way that patients are injected intra-articular injection of 2 cc of normal saline with 2 cc of hyaluronic acid in three times at 0, 2 and 4 months intervals in the operating room of Royan Clinic. At the time of injection, the patient's knee is sterilized and the orthopedic surgeon will inject into the joint space under sterile conditions. After the injection, the patient is monitored for 2 hours and after this period, if there is no problem with the necessary medication and care instructions and explanation of warning signs will be discharged.
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Category
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Treatment - Drugs
2
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Description
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Intervention group: Patients receiving 3 doses of normal saline containing 20 million Mesenchymal cells derived from allogenic umbilical cord tissue + Hyaluronic acid The method of intervention will be that patients in three times at intervals of 0, 2 and 4 months in the operating room of Royan Clinic, injected with 2 cc of normal saline containing 20 million mesenchymal stem cells derived from non-native umbilical cord tissue with 2 cc of hyaluronic Acids are placed. On the day of cell transplantation, it is sent to this center for injection by the clean room of Cell Tech Pharmed factory in a vial and inside a box. The patient's knee is sterilized and the orthopedic surgeon will inject into the joint space under sterile conditions. After the injection, the patient is monitored for 2 hours and after this period, if there is no problem with the necessary medication and care instructions and explanation of warning signs will be discharged.
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Category
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Treatment - Other
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Royan Stem Cell Technology Company
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Proportion provided by this source
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80
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Other
2
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Cell-Tech Pharmed
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Proportion provided by this source
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20
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Other
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available
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Title and more details about the data/document
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The information and data will be published as an article after reviewing and verifying them. All data is potentially shareable after unidentified individuals.
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When the data will become available and for how long
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After following the patients and collecting data, checking the safety and efficiency of cell injection and then writing the article, which is done about 3 months after the follow-up, the data file will be published.
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To whom data/document is available
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Access to the documents of this research is not limited to academic and scientific researchers, and specialists working in other centers can also access these documents.
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Under which criteria data/document could be used
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Designing similar studies in other academic centers
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From where data/document is obtainable
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e.afzal@rsct.it
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What processes are involved for a request to access data/document
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Within 1-2 months after application. Applicants for access to the research documents must provide evidence of their activity in the relevant field and their need for this data along with their application email.
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Comments
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