Evaluation of safety and efficacy of Intravenous and Interatechal injection of autologous bone marrow-drived mesenchymal stem cells in RRMS patients under fingolimod therapy: randomized clinical trial with control group, Phase 2 and 3.
ٍEvaluation of injection of mesenchymal stem cells into RRMS patients who are under Fingolimod therapy.
Design
This is a Phase 2-3 study that examines the safety and efficacy of intravenous and intrathecal injections of autologous bone marrow mesenchymal stem cells with fingolimod compared to fingolimod alone in MS patients. The study employed a two-arm, single-blind randomized controlled
design and Superiority.
Settings and conduct
120 patients with RRMS were divided into two groups of 60 each. First group patients received only fingolimod and second group patients receive fingolimod plus 2 Injections of autologous mesenchymal stem cells (1 intravenously and 1 Intrathecally). Two groups of neurologists work in this study: the first group selects patients and initiates treatment that is not blind to the study. The second group conducts clinical follow-up of patients that is blind to the study. Bone marrow aspirations, stem cell and drug administrations are performed in hospitals. Cell cultures are performed in GMP grade clean rooms along with quality control tests. Follow-up, examination and paraclinical tests are performed at physicians office or hospitals.
Participants/Inclusion and exclusion criteria
Inclusion criteria
1. Age: 18 to 55
2. Clinical diagnosis of RRMS.
3. EDSS less than 6
Exclusion criteria
1. A history of another underlying disease Including neoplasm.
2. Positive laboratory tests for hepatitis B, C, HIV, HTLV JCV.
3. The presence of any metallic particles implant in the body, due to the limitations in performing the MRI
Intervention groups
1. Control group: Fingolimod is prescribed only in accordance with the routine protocol.
2. Test group: Fingolimod is prescribed in addition to mesenchymal stem cells.
Main outcome variables
Safety: Study of side effects in both groups over 12 months.
Efficacy: Clinical relapse rate during one year follow-up.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20191004044975N1
Registration date:2020-01-10, 1398/10/20
Registration timing:prospective
Last update:2020-01-10, 1398/10/20
Update count:0
Registration date
2020-01-10, 1398/10/20
Registrant information
Name
Mandana Mohyeddin Bonan
Name of organization / entity
SinaCell research and production Co.
Country
Iran (Islamic Republic of)
Phone
+98 21 7625 0661
Email address
mandanamohyeddin@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-02-04, 1398/11/15
Expected recruitment end date
2021-10-22, 1400/07/30
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of safety and efficacy of Intravenous and Interatechal injection of autologous bone marrow-drived mesenchymal stem cells in RRMS patients under fingolimod therapy: randomized clinical trial with control group, Phase 2 and 3.
Public title
Investigating the effect of the bone marrow-drived mesenchymal stem cells in MS patients under fingolimod therapy.
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Clinical diagnosis of RRMS.
EDSS less than 6
Patients who have used the first line of DMD for one year and who have had a clinical attack or deteriorating brain and Cervical Spinal Cord MRI findings in the one past-year.
Disease progression or the onset of re-attack or deteriorating MRI findings within the one past- year prior to inclusion
Normal macula.
Patients' written consent to participate in the study.
Exclusion criteria:
Proven clinical attack 30 days prior to the patient's entry into the study.
Use of corticosteroid drug (MePDN) 30 days prior to the patient's entry into the study.
Having infectious diseases.
A history of another underlying disease Including neoplasm.
The presence of clear disorders in consciousness and cognition.
Creatinine greater than 1.7 mg/dl Or Liver enzymes three times the upper limit of the normal range or more, Or a white blood cell count less than 3,000/mm3 and hemoglobin less than 10.7 g/dL.
Treatment with cytotoxic drugs 6 months before starting the study.
Positive laboratory tests for hepatitis B, C, HIV , HTLV, JCV, or syphilis.
The presence of any contain metallic particles implant in the body, due to the limitations in performing the MRI
Positive TB (PPD) test.
Pregnancy or pregnancy intention during treatment in female patients.
Age
From 18 years old to 55 years old
Gender
Both
Phase
2-3
Groups that have been masked
Care provider
Outcome assessor
Data analyser
Sample size
Target sample size:
120
Randomization (investigator's opinion)
Randomized
Randomization description
The "http://www.randomization.com" site will be used to generate random code.The permuted-block randomization method was used to balance the number of patients and to randomly assign patients to the control and intervention group and the control group.The blocks vary in size in each disease category. (with block size =10 and 4)
Blinding (investigator's opinion)
Single blinded
Blinding description
Unlike Fingolimod Therapy, the type of cell therapy intervention requires bone marrow aspiration . Ethically, the patients are not blinded for the intervention and, consequently, the physician who applies the intervention is not blind to the treatment of the patients. But clinical examinations, laboratory results and evaluations (such as MRI imaging, etc.) will be performed by physicians who are unaware of the patient's specific treatment, and to determine the final data, the statistical analyzer does not know the actual treatment and the groups are locked (A and B labeled) and sent for statistical analysis.
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Tehran University of medical sciences
Street address
Poursina Ave.
City
Tehran
Province
Tehran
Postal code
3439123900
Approval date
2019-09-03, 1398/06/12
Ethics committee reference number
IR.TUMS.VCR.1398.537
2
Ethics committee
Name of ethics committee
Ethics committee of Shahid Beheshti University of medical sciences
Street address
Velenjak
City
Tehran
Province
Tehran
Postal code
1971653313
Approval date
2019-08-20, 1398/05/29
Ethics committee reference number
IR.SBMU.REC.1398.049
Health conditions studied
1
Description of health condition studied
Multiple sclerosis
ICD-10 code
G35
ICD-10 code description
Multiple sclerosis
Primary outcomes
1
Description
safety
Timepoint
Month of 1,2,3,4,5,6,8,10 and 12
Method of measurement
Evaluation of side effects during one year after intervention .
2
Description
Efficacy
Timepoint
Month of 1,2,3,4,5,6,8,10 and 12
Method of measurement
Number of clinical relapses during one year after intervention .
Secondary outcomes
1
Description
The number of gadolinium enhancing lesions in comparison to baseline in two groups.
Timepoint
In the months of 0,6,12
Method of measurement
MRI
2
Description
Prevention of EDSS progression in comparison of baseline EDSS in two groups.
Timepoint
In the months of 0,1,2,3,4,5,6,8,10 and 12
Method of measurement
The Kurtzke Expanded Disability Status Scale (EDSS) method.
3
Description
Visual evoked potential
Timepoint
In the months of 0,3,6,12
Method of measurement
Electrooculogram
4
Description
Total survival rate of the patient
Timepoint
One year follow up
Method of measurement
Visual
5
Description
Progression Free Survival rate
Timepoint
One year follow up
Method of measurement
The results of clinical and para-clinical evaluation.
6
Description
The number of new T2 lesions in comparison to baseline in two groups.
Timepoint
The month of 0, 6, 12
Method of measurement
MRI
Intervention groups
1
Description
Intervention group: This group received the fingolimod and autologous bone marrow derived mesenchymal stem cells proliferating in the culture medium, at the same time . The cells are suspended in serum physiology medium enriched with human serum albumin, which is administered twice. For the first time intravenously in a dose of 1 to 2 million per kg body weight of the patient and the second time, after about two weeks, Intrathecally applied in a dose of / 0.5. Millions per Kg body weight of the patient.
Category
Treatment - Other
2
Description
Control group: This group will received only a single dose of fingolimod (0.5Milligrams Danelvin capsule , Nano-Alvand Company) daily by the end of the study.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Loghman Hakim Hospital
Full name of responsible person
Hossin Pakdaman
Street address
Lashghar Intersection. Makhsus St.
City
Tehran
Province
Tehran
Postal code
1333625445
Phone
+98 21 5541 9005
Fax
+98 21 5541 9005
Email
loghman.hospital@sbmu.ac.ir
Web page address
https://www.drsaina.com
2
Recruitment center
Name of recruitment center
Gandhi Hospital
Full name of responsible person
saeed shahbeigi
Street address
Ghandhi Street
City
Tehran
Province
Tehran
Postal code
1517717111
Phone
+98 21 4260 3000
Fax
+98 21 4260 3000
Email
info@gandhihospital.ir
Web page address
http://gandihospital.ir/
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Vice-presidency for science and technology
Full name of responsible person
Amir Ali Hmidieh
Street address
North Sheikh Bahayee St. Ladan Alley
City
Tehran
Province
Tehran
Postal code
1991745681
Phone
+98 21 8353 2471
Fax
+98 21 8353 2375
Email
pr@stemcell.isti.ir
Web page address
http://isti.ir/
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Vice-presidency for science and technology
Proportion provided by this source
60
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other
2
Sponsor
Name of organization / entity
Sinacell research and production company
Full name of responsible person
ehsan seyedjafari
Street address
No. 162, Noaver 16, Pardis Technology Park
City
Tehran
Province
Tehran
Postal code
1657163871
Phone
+98 21 7625 0661
Fax
+98 21 7625 0664
Email
info.sinacell@gmail.com
Web page address
http://sinacellco.com/
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Sinacell research and production company
Proportion provided by this source
40
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other
Person responsible for general inquiries
Contact
Name of organization / entity
Sinacell research and production Company
Full name of responsible person
Mandana Mohyeddin Bonab
Position
Technical Director
Latest degree
Ph.D.
Other areas of specialty/work
Stem cell researcher
Street address
No. 19, First East Ave., 24 meter Blvd., Saadatabad
City
Tehran
Province
Tehran
Postal code
1997778714
Phone
+98 21 2206 6928
Email
mohyeddin@sina.tums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Brain Mapping Research Center
Full name of responsible person
saeed shahbeigi
Position
researcher
Latest degree
Subspecialist
Other areas of specialty/work
Neurology
Street address
Loghman HakimHospital, South Karghar Ave., Kamali St.,,
City
Tehran
Province
Tehran
Postal code
1333631151
Phone
+98 21 5541 0044
Fax
+98 21 5541 0044
Email
bmrc@sbmu.ac.ir
Web page address
http://bmrc.sbmu.ac.ir/
Person responsible for updating data
Contact
Name of organization / entity
Ministry of Health and Medical Education
Full name of responsible person
Abbas Najjari
Position
Manager of research and technology data
Latest degree
Ph.D.
Other areas of specialty/work
Health Technology Assessment
Street address
Eyvanak Blvd., Qods Town
City
Tehran
Province
Tehran
Postal code
1467664961
Phone
+98 21 8145 5131
Email
najjabb@yahoo.com
Web page address
http://behdasht.gov.ir/
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Yes - There is a plan to make this available
Title and more details about the data/document
Information about the main outcome will be shared.
When the data will become available and for how long
Data will be available six months after the results are published.
To whom data/document is available
The data will be made available to academic researchers and those working in the fields of neurology and MS.
Under which criteria data/document could be used
By contacting the project executives and
Contact the project sponsor
What processes are involved for a request to access data/document
The request will first be emailed to one of the addresses. The request will then be processed and the requested data will be sent to the email address of the requestor or the reason for the failure to respond. This process may take about two weeks.