Protocol summary

Study aim
Evaluation of the safety of repeated intravenous injection of foreign bone marrow-derived clonal mesenchymal stem cells in patients with rheumatoid arthritis
Design
Patients will enter the study in a regular order. The first patient is monitored for 3 months and if cell therapy is safe, the next patient will enter the study 3 months later and will be monitored for 2 months. Again, provided it was safe, the treatment performed during this period, the third patient will enter the study. This time it will be followed up for a month and in the absence of severe and life-threatening complications, the next patients will be included in the study.
Settings and conduct
Location: Shariati Hospital and Imam Khomeini Hospital and Rheumatism Center of Iran Clinical and paraclinical studies before stem cell injection include initial clinical examinations, necessary laboratory tests, and related questionnaires.
Participants/Inclusion and exclusion criteria
People aged 18 to 60 years with refractory rheumatoid arthritis who willingly participate in the study are included. People with other chronic diseases, allergies or any unstable clinical conditions as well as pregnancy and lactation and people who plan to become pregnant during the study or for any reason do not use safe contraceptive methods are not included in the study.
Intervention groups
Injection material: Clonal mesenchymal stem cells derived from allogeneic bone marrow tissue Injection rate: 1 million cells per kilogram of body weight (70 million allogeneic bone marrow-derived mesenchymal stem cells) in sac form • Injection method: Intravenous/ 3 times Interval between each injection: 1 month
Main outcome variables
No side effects, including short-term and long-term, systemic or local, and severe or mild, related and unrelated to cell therapy (1 week and 1, 2, 3, 4 and 6 months after the first injection) By reviewing CTCAE v4

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20080728001031N29
Registration date: 2021-04-07, 1400/01/18
Registration timing: prospective

Last update: 2021-04-07, 1400/01/18
Update count: 0
Registration date
2021-04-07, 1400/01/18
Registrant information
Name
Nasser Aghdami
Name of organization / entity
Royan Institute
Country
Iran (Islamic Republic of)
Phone
+98 21 2356 2000
Email address
nasser.aghdami@royaninstitute.org
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-04-21, 1400/02/01
Expected recruitment end date
2022-04-21, 1401/02/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Safety of multiple intra-venous allogeneic clonal bone marrow derived mesenchymal stromal cells transplantation in patients with refractory rheumatoid arthritis: An interventional multicenter clinical trial phase I/II
Public title
Safety of multiple intra-venous allogeneic clonal bone marrow derived mesenchymal stromal cells transplantation in patients with refractory rheumatoid arthritis
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Diagnosis of Rheumatoid Arthritis According to the American Rheumatism Association for at least 6 months prior to enrollment Having refractory RA means not responding to: a.At least 1 synthetic conventional anti Rheumatoid drug (synthetic conventional DMARD) b.At least 1 biologic drug DMARD or targeted synthetic DMARD in the last 6 weeks Willingness to participate in the study and sign the study informed consent form Patients of childbearing age (male and female) should agree to use an appropriate method of contraception.
Exclusion criteria:
Taking Biological and Targeted conventional Anti Rheumatoid drugs in the last 6 weeks Any live vaccination in 8 weeks before enrollment until the end of the study History of malignancy and treatment with anticancer drugs in the last 5 years History of bleeding or abnormal clotting Severe mental or neurological disorders that affect informed consent or the presentation or observation of side effects Chronic or active systemic infectious disease (HIV, HBS, HCV and HTLV1) Autoimmune disease other than RA Acquired or congenital immunodeficiency such as AIDS, CVID, lymphoma History of cerebrovascular diseases such as stroke, aneurysm and malformation of cerebral vessels, thrombosis and vascular stenosis Pregnancy and lactation and people who plan to become pregnant during the study or do not use safe contraception for any reason Pulmonary embolism or anti phospholipid syndrome Known allergy or history of allergies to medicinal products, eggs and blood products History of chronic obstructive pulmonary disease or known lung disease other than mild asthma treated with bronchodilators Patient with unstable clinical condition: uncontrolled diabetes, heart disease, advanced renal or hepatic impairment Any condition that, according to the lead researcher, cell therapy is inappropriate for the patient
Age
From 18 years old to 60 years old
Gender
Both
Phase
1-2
Groups that have been masked
No information
Sample size
Target sample size: 6
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
Jihad research ethics committee
Street address
No.1270, Jihad central office, In front of the main door of Tehran University, Enghelab Ave.
City
Tehran
Province
Tehran
Postal code
14155 - 4364
Approval date
2021-01-24, 1399/11/05
Ethics committee reference number
IR.ACECR.REC.1399.003

Health conditions studied

1

Description of health condition studied
Rheumatoid Arthritis
ICD-10 code
M05.60
ICD-10 code description
Rheumatoid arthritis of unspecified site with involvement of other organs and systems

Primary outcomes

1

Description
Evaluation of the safety of repeated intravenous injection of allogeneic bone marrow-derived clonal mesenchymal stromal cells in patients with rheumatoid arthritis
Timepoint
one week, 1, 2, 3, 4, and 6 months after first injection
Method of measurement
CTCAE v4 questionnaire

Secondary outcomes

1

Description
20% improvement in ACR
Timepoint
Before injection, one week, 1, 2, 3, 4 and 6 months after first injection
Method of measurement
software

2

Description
50% improvement in ACR
Timepoint
Before injection, one week, 1, 2, 3, 4 and 6 months after first injection
Method of measurement
software

3

Description
70% improvement in ACR
Timepoint
Before injection, one week, 1, 2, 3, 4 and 6 months after first injection
Method of measurement
software

4

Description
Improving in health standards
Timepoint
Before injection, one week, 1, 2, 3, 4 and 6 months after first injection
Method of measurement
HAQ questionnaire

5

Description
Improvement of pain
Timepoint
Before injection, one week, 1, 2, 3, 4 and 6 months after first injection
Method of measurement
VAS score

6

Description
Improvement in LAB tests (, IL-10, Th 17, Treg, Anti-CCP, CRP, RF, ESR, GATA3 transcription factor, IL-17, TNF-α (ELISA test))
Timepoint
Before injection, 4 and 6 months after injection
Method of measurement
blood test

Intervention groups

1

Description
Intervention group: Three intravenous injections of 1 million per kg of clonal mesenchymal stromal cells derived from allogeneice bone marrow tissue suspended in 15 ml normal saline at one-month intervals
Category
Treatment - Drugs

Recruitment centers

1

Recruitment center
Name of recruitment center
Royan institute
Full name of responsible person
Masood Vosough
Street address
Royan Alley, Eastern Hafez St, Northern Banihashem St, 45 m Ghasem Soleymani Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2251 8388
Email
masvos@yahoo.com

2

Recruitment center
Name of recruitment center
Iran Rheumatism Center
Full name of responsible person
Ahmadreza Jamshidi
Street address
No.70, Khosravi alley, North Kargar Blvd
City
Tehran
Province
Tehran
Postal code
3341299811
Phone
+98 21 8800 5141
Email
jamshida@tums.ac.ir

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Royan institute
Full name of responsible person
Abdolhossein Shahverdi
Street address
Royan Alley, Eastern Hafez St, Northern Banihashem St, 45 m Ghasem Soleymani Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2356 2211
Email
shahverdi@royaninstitute.org
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Royan institute
Proportion provided by this source
100
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
Academic

Person responsible for general inquiries

Contact
Name of organization / entity
Royan Institute
Full name of responsible person
Hoda Madani
Position
Researcher
Latest degree
Medical doctor
Other areas of specialty/work
Cell Science and Application
Street address
Royan Alley, Eastern Hafez St, Northern Banihashem St, 45 m Ghasem Soleymani Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2356 2211
Email
hoda62_m@yahoo.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Royan institute
Full name of responsible person
Nasser Aghdami
Position
Associate Professor
Latest degree
Ph.D.
Other areas of specialty/work
Immunology
Street address
Royan Alley, Eastern Hafez St, Northern Banihashem St, 45 m Ghasem Soleymani Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2251 8388
Email
nasseragh@gmail.com

Person responsible for updating data

Contact
Name of organization / entity
Royan institute
Full name of responsible person
Hoda Madani
Position
Researcher
Latest degree
Medical doctor
Other areas of specialty/work
General Practitioner
Street address
Royan Alley, Eastern Hafez St, Northern Banihashem St, 45 m Ghasem Soleymani Highway
City
Tehran
Province
Tehran
Postal code
1665664511
Phone
+98 21 2251 8388
Email
hoda62_m@yahoo.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD
There is no further information
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be 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
Undecided - It is not yet known if there will be 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
Undecided - It is not yet known if there will be a plan to make this available
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