1. Objectives:
Evaluation of mesenchymal stem cell therapy effects on cellular immune response in refractory rheumatoid arthritis patients.
2. Design:
This study is a phase 1 clinical trial.
3. Setting and conduct:
Autologous bone marrow derived mesenchymal stem cells will be obtained by bone marrow aspiration and will be cultured in Minimum Essential Medium-Alpha for 4 weeks in standard clean room and then transfused to RA patients intravenously.
4. Participants including major eligibility criteria:
21 refractory rheumatoid arthritis patients who show resistance to non biological DMARDs after 6 to 12 months will be enrolled in this study.
5. Intervention:
A single intravenous administration of autologous bone marrow derived mesenchymal stem cells(2000000 to 3000000 cells/Kg) to patients with resistance to non-biological DMARDs.
6. Main outcome measures(variables):
Finding of mesenchymal stem cell therapy effects on the cellular immune responses.
General information
Acronym
IRCT registration information
IRCT registration number:IRCT2015102824760N1
Registration date:2016-06-12, 1395/03/23
Registration timing:prospective
Last update:
Update count:2
Registration date
2016-06-12, 1395/03/23
Registrant information
Name
Mojgan Mohammadi
Name of organization / entity
Mashhad University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 51 3841 2081
Email address
mohammadimzh@mums.ac.ir
Recruitment status
Recruitment complete
Funding source
Research Chancellor, Mashhad University of Medical Sciences
Council for Stem Cell Sciences and Technologies, Presidency of the Islamic Republic of Iran, Vice presidency for Science and Technology
Expected recruitment start date
2016-06-19, 1395/03/30
Expected recruitment end date
2018-06-20, 1397/03/30
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of Mesenchymal stem cell therapy effects on the cellular immune response in refractory rheumatoid arthritis patients
Public title
Evaluation of Mesenchymal stem cell therapy effects on the cellular immune response in refractory rheumatoid arthritis patients
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Resistant RA patients to non-biological DMARDs; Treated RA patients by non-biological drugs; Treated RA patients by Prednisolone, Hydroxychloroquine, Sulfasalazine and Methotrexate; patients age between 35-60 years; Refractory RA patients with no other rheumatologic disorders and inflammatory diseases.
Exclusion criteria:
Non-resistant RA patients to non-biological DMARDs.
Age
From 35 years old to 60 years old
Gender
Both
Phase
1
Groups that have been masked
No information
Sample size
Target sample size:
21
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Mashhad University of Medical Sciences
Street address
Qoreishi Bulding, Daneshgah St
City
Mashhad
Postal code
91375-345
Approval date
2015-11-21, 1394/08/30
Ethics committee reference number
IR.MUMS.REC.1394.529
Health conditions studied
1
Description of health condition studied
Rheumatoid arthritis
ICD-10 code
M05
ICD-10 code description
Diseases of the musculoskeletal system and connective tissue
Primary outcomes
1
Description
Interleukin-1
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
pg/ml using ELISA assay
2
Description
TNF-alpha
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
pg/ml using ELISA assay
3
Description
Interleukin-4
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
pg/ml using ELISA assay
4
Description
Interleukin-10
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
pg/ml using ELISA assay
5
Description
TGF-beta
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
Frequency and the intensity of stained cells in the ELISPOT assay
6
Description
Interleukin-17
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
pg/ml using ELISA assay
7
Description
T-bet transcription factor
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
The copy number of desired gene using RT-PCR assay
8
Description
GATA3 transcription factor
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
The copy number of desired gene using RT-PCR assay
9
Description
FOXP3 transcription factor
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
The copy number of desired gene using RT-PCR assay
10
Description
ROR-gamma T transcription factor
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
The copy number of desired gene using RT-PCR assay
11
Description
T helper cells
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
Frequency of desired cells using flow cytometry technique
12
Description
Regulatory T cells
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
Frequency of desired cells using flow cytometry technique
13
Description
Th17
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
Frequency of desired cells using flow cytometry technique
14
Description
Disease activity score (DAS)
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
Clinical and laboratory findings
15
Description
Visual analogue scale (VAS)
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
The amount of pain that a patient feels
16
Description
Erythrocyte sedimentation rate(ESR)
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
Erythrocyte sedimentation rate in millimeters
17
Description
C-reactive protein (CRP)
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
Latex agglutination test
18
Description
Rheumatoid factor(RF)
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
Latex agglutination test
19
Description
Anti-cyclic citrullinated peptide (anti-CCP)
Timepoint
Before intervention and after 1, 6, 12 months follow up
Method of measurement
ELISA test
Secondary outcomes
1
Description
Anaphylaxis
Timepoint
After IV infusion of MSCs
Method of measurement
Clinical manifestations, hypotension and hypoglycemia
2
Description
Differentiation of MSCs to unwanted cells
Timepoint
After IV infusion of MSCs
Method of measurement
Clinical manifestations
Intervention groups
1
Description
A single intravenous administration of autologous bone marrow derived mesenchymal stem cells(2000000 to 3000000 cells/Kg).
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Emam Reza Hospital
Full name of responsible person
ِDr. Zhale shariati sarabi
Street address
Ebne Sina Ave, Emam Reza Sq
City
Mashhad
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Research Chancellor, Mashhad University of Medical Sciences
Full name of responsible person
Dr. Mojgan Mohammadi
Street address
BuAli research institute, BuAli Sq, Ferdowsi Sq
City
Mashhad
Grant name
Grant code / Reference number
931523
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Research Chancellor, Mashhad University of Medical Sciences
Proportion provided by this source
Public or private sector
empty
Domestic or foreign origin
empty
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
empty
2
Sponsor
Name of organization / entity
Council for Stem Cell Sciences and Technologies, Presidency of the Islamic Republic of Iran, Vice pr
Full name of responsible person
Dr. Amir Ali Hamidieh
Street address
No 21, Ladan Alley, North Sheikh Bahayee St, MollaSadra St, Vanak Sq
City
Tehran
Grant name
Grant code / Reference number
122
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Council for Stem Cell Sciences and Technologies, Presidency of the Islamic Republic of Iran, Vice pr
Proportion provided by this source
Public or private sector
empty
Domestic or foreign origin
empty
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
empty
Person responsible for general inquiries
Contact
Name of organization / entity
Mashhad University of Medical Sciences
Full name of responsible person
Mohsen Ghoryani
Position
Ph.D student in Immunology
Other areas of specialty/work
Street address
BuAli Research Institute, BuAli Sq, Ferdowsi Sq
City
Mashhad
Postal code
9188986439
Phone
+98 51 3604 1865
Fax
+98 51 3711 2596
Email
ghoryanim931@mums.ac.ir
Web page address
Person responsible for scientific inquiries
Contact
Name of organization / entity
Mashhad University of Medical Sciences
Full name of responsible person
Mojgan Mohammadi
Position
Ph.D
Other areas of specialty/work
Street address
BuAli Research Institute, BuAli Square, Ferdowsi Sq