Evaluation of the safety and tolerability of the injection of mesenchymal stem cells derived from the human placenta in patients with systemic sclerosis
Design
The study is a single-arm, non-randomized, non-blinded Phase 1 clinical trial in 10 patients with severe systemic sclerosis.
Settings and conduct
In a cleanroom facility, placental-derived Mesenchymal Stem Cells are manufactured according to Good Manufacturing Practices (GMP) rules. After passing Quality Control tests, 1 million/kg of PLMSCs are packed in a bag and injected intravenously (for 15 minutes). The injections are done in university hospitals located in Tehran.
Participants/Inclusion and exclusion criteria
Inclusion criteria:1- Having severe systemic sclerosis 2- The modified Rodnan skin score (MRSS) of more than 15 without any restrictions on the duration of the disease 3- Involvement of at least one major organ that is exclusively caused by systemic sclerosis; including proven lung involvement, cardiac involvement 4-Inadequate response to treatment according to the doctor's or patient's opinion, or the observation of more than three months of treatment complications
Exclusion criteria: 1-Pregnancy 2-threatening end organ damage 3-Uncontrolled blood pressure 4-severe mental disorder 5-uncontrolled acute or chronic infection 6- simultaneously suffering from neoplasm or myelodysplasia
Intervention groups
The intervention group includes patients with severe systemic sclerosis. Each patient receives intravenously a single dose of mesenchymal stem cells in the amount of one million cells per kilogram of body weight. The patients also receive other usual treatments.
Main outcome variables
Safety was evaluated based on the rate of adverse events (grades 3 to 5) related to cell injection within 7 days after injection (using the National Cancer Institute of Common Terminology Criteria for Adverse Events (CTCAE) classification).
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200621047859N5
Registration date:2024-09-26, 1403/07/05
Registration timing:registered_while_recruiting
Last update:2024-09-26, 1403/07/05
Update count:0
Registration date
2024-09-26, 1403/07/05
Registrant information
Name
Ramin Sarrami Forooshani
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8879 6003
Email address
rsf1351@gmail.com
Recruitment status
recruiting
Funding source
Expected recruitment start date
2024-09-22, 1403/07/01
Expected recruitment end date
2025-10-26, 1404/08/04
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluating the safety and feasibility of human placenta-derived mesenchymal stem cell injection in systemic sclerosis. A pilot study
Public title
Evaluating the safety of mesenchymal stem cell in systemic sclerosis
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Having severe systemic sclerosis according to the diagnostic criteria of the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR)
The modified Rodnan skin score (mRSS) >15 without any restrictions on the duration of the disease
Involvement of at least one major organ that is exclusively caused by systemic sclerosis; including one or more of the following: proven lung involvement with impaired diffusion capacity for carbon monoxide (DLCO) or predicted FVC drop below 80% or evidence of interstitial lung disease in chest X-ray and/or high-resolution imaging computed tomography (HRCT) scan cardiac involvement including: edema or inflammation in heart MRI, mild to severe pericardial effusion, congestive heart failure, atrial or ventricular arrhythmias including recurrent atrial fibrillation or flutter, recurrent atrial paroxysmal tachycardia, conduction abnormalities (2nd or 3rd degree atrioventricular block)
Inadequate response to treatment according to the doctor's or patient's opinion, or the observation of more than three months of treatment complications, which are often caused by the following drugs: methotrexate 25 mg subcutaneous (or as tolerated) per week mycophenolate mofetil 2-3 gm/d (or as tolerated)
Exclusion criteria:
Pregnancy or unwillingness to use appropriate birth control methods
Threatening end organ damage includes; Pulmonary failure, Heart failure in echocardiography, Pulmonary hypertension
Simultaneously suffering from neoplasm or myelodysplasia
Uncontrolled blood pressure
Uncontrolled acute or chronic infection or high probability of viral infections
Significant malnutrition with body mass index (BMI) < 18 kg/m2
Severe mental disorder
Bone marrow failure
Not accompanying the patient
Simultaneous participation of the patient in other researches or researches that are accompanied by giving medicine
Inability to provide informed consent
Age
From 18 years old
Gender
Both
Phase
1
Groups that have been masked
No information
Sample size
Target sample size:
10
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
Research Ethics Committees of Research Institute for Hematology, Oncology and Cell Therapy - Tehran
Street address
Dr.Shariati Hospital, Kargar Shomali Ave
City
Tehran
Province
Tehran
Postal code
1411713135
Approval date
2023-12-13, 1402/09/22
Ethics committee reference number
IR.TUMS.HORCSCT.REC.1402.047
Health conditions studied
1
Description of health condition studied
systemic sclerosis
ICD-10 code
ICD-10 code description
Primary outcomes
1
Description
Safety assessment based on the rate of adverse events (grade 3 to 5) related to cell injection
Timepoint
up to 7days after injection
Method of measurement
Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Secondary outcomes
1
Description
Change in Medsger Disease Severity Scale (DSS)
Timepoint
between 0, 3, 6, 9 and 12 months
Method of measurement
The patients follow up
Intervention groups
1
Description
Intervention group: patients with severe systemic sclerosis according to diagnostic criteria. This group will receive about 10^6 cells/Kg Good manufacturing practices (GMP)-grade mesenchymal stem cells infusion over 10 minutes. The common treatments of patients will not be stopped.