Rheumatoid ArthritisPhase 1NCT03333681
Evaluation of Stem Cell Therapy Effects on the Immune Response in Rheumatoid Arthritis Patients
A Phase 1 study testing Autologous mesenchymal stem cells in people with Rheumatoid Arthritis, run by Mashhad University of Medical Sciences.
Trial summary
1. Objectives: Evaluation of mesenchymal stem cell therapy effects on cellular and humoral immune responses in refractory rheumatoid arthritis (RA) patients. 2. Design: This study has been performed as a phase 1 clinical trial. 3. Read more about this study
- Who is it for?
- Ages 35 to 60 years, women only
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Autologous mesenchymal stem cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- No sites listed yet
- Study dates
- 20 Jun 2016to 15 Sep 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- Non-resistant RA patients to non-biological DMARDs.
About this study
Official title: Evaluation of Mesenchymal Stem Cell Therapy Effects on the Cellular and Humoral Immune Responses and Additionally Study on the Effect of Chemokines in Homing of the Immune Cells in Refractory Rheumatoid Arthritis Patients
- Objectives: Evaluation of mesenchymal stem cell therapy effects on cellular and humoral immune responses in refractory rheumatoid arthritis (RA) patients.
- Design: This study has been performed as a phase 1 clinical trial.
- Setting and conduct: Autologous bone marrow derived mesenchymal stem cells were obtained by bone marrow aspiration and cultured in Minimum Essential Medium-Alpha (MEM-alpha) for 4 weeks in standard clean room and then transfused to RA patients intravenously.
- Participant's major eligibility criteria is as follows: Ten refractory rheumatoid arthritis patients who show resistance to non biological Disease-modifying antirheumatic drugs (DMARDs) after 6 to 12 months have been enrolled in this study.
- Intervention: A single dose of intravenous autologous bone marrow derived mesenchymal stem cells have been administered into patients with resistance to non-biological DMARDs.
- Main outcome measures (variables): Finding of mesenchymal stem cell therapy effects on the cellular and humoral immune responses and evaluation of the effect of chemokines in homing of immune cells following the intervention.
Read the detailed description
Refractory rheumatoid arthritis patients who met the inclusion/exclusion criteria have been selected. After signing informed consent form, autologous stem cells were obtained by bone marrow aspiration. Isolation and culture (3 to 4 weeks in MEM-alpha medium) of mesenchymal stem cells (MSCs) were performed in accredited good manufacturing practices (GMP) clean room. A panel of cluster of differentiation (CD) markers including CD105, CD166, CD44, CD45, CD90, and CD34 were checked for making sure about differentiation of cells into MSCs after 3-4 weeks of cell culture. Viability of MSCs was checked by Trypan blue testing and all of the cultivations were negative for bacterial contamination. A single dose of 1000000 to 2000000 mesenchymal stem cells/kg infused into patients intravenously. To prevent anaphylactic reactions, a single intravenous dose of hydrocortison (100 ml) and oral dimenhydrinate (10 ml) were administered before MSCs infusion into patients. The effects of mesenchymal stem cells on the cellular and humoral immune responses and also the role of chemokines in homing of immune cells were studied at time points 1, 6 and 12 months after intravenous administration of MSCs in refractory rheumatoid arthritis.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Autologous mesenchymal stem cells
- Keywords
- Rheumatoid arthritis, Stem Cells, Cellular immunity, Humoral immunity, chemokines, homing of immune cells
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous mesenchymal stem cellsBiological
A single intravenous administration of autologous bone marrow derived mesenchymal stem cells(1000000 to 2000000 cells/Kg)
| Study group | Role | What they receive |
|---|---|---|
| Refractory rheumatoid arthritis patients | Experimental | Autologous mesenchymal stem cells Receives: Biological: Autologous mesenchymal stem cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of mesenchymal stem cells therapy on the percentage of regulatory T cells
Percentage change in regulatory T cells from baseline which is analysed by fluorescence-activated cell sorting (FACS)
Measured: At 0 and 6 months follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2017
- Study start20 Jun 2016
- Primary completion15 Aug 2018
- Study completion15 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mashhad University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Mojgan Mohammadi, Mashhad University of Medical Sciences
- Investigators
- Mojgan Mohammadi, Ph.D, Principal investigator, Mashhad University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03333681
- Sponsor's protocol ID
- 931523
- Other IDs
- 122
- Status last verified
- Mar 2019
- First submitted
- 14 Sep 2017
- Last updated
- 13 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Alvaro-Gracia JM, Jover JA, Garcia-Vicuna R, Carreno L, Alonso A, Marsal S, Blanco F, Martinez-Taboada VM, Taylor P, Martin-Martin C, DelaRosa O, Tagarro I, Diaz-Gonzalez F. Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial. Ann Rheum Dis. 2017 Jan;76(1):196-202. doi: 10.1136/annrheumdis-2015-208918. Epub 2016 Jun 7.
PubMed 27269294Liang J, Li X, Zhang H, Wang D, Feng X, Wang H, Hua B, Liu B, Sun L. Allogeneic mesenchymal stem cells transplantation in patients with refractory RA. Clin Rheumatol. 2012 Jan;31(1):157-61. doi: 10.1007/s10067-011-1816-0. Epub 2011 Aug 12.
PubMed 21837432Wang L, Wang L, Cong X, Liu G, Zhou J, Bai B, Li Y, Bai W, Li M, Ji H, Zhu D, Wu M, Liu Y. Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy. Stem Cells Dev. 2013 Dec 15;22(24):3192-202. doi: 10.1089/scd.2013.0023. Epub 2013 Oct 4.
PubMed 23941289Rahimi Khorashad M, Ghoryani M, Gowhari Shabgah A, Shariati-Sarabi Z, Tavakkol Afshari J, Mohammadi M. The Effects of Mesenchymal Stem Cells on the Gene Expression of TGF-beta and IFN-gamma in Patients with Rheumatoid Arthritis. Iran J Allergy Asthma Immunol. 2023 Apr 30;22(2):183-189. doi: 10.18502/ijaai.v22i2.12679.
PubMed 37496411
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Mesenchymal Stem Cell Therapy Effects on the Cellular and Humoral Immune Responses and Additionally Study on the Effect of Chemokines in Homing of the Immune Cells in Refractory Rheumatoid Arthritis Patients
- ClinicalTrials.gov ID
- NCT03333681
- Acronym / sponsor ID
- 931523
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid arthritis, Stem Cells, Cellular immunity, Humoral immunity, chemokines, homing of immune cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Mashhad University of Medical SciencesUniversity, hospital or other
- Study start
- 20 Jun 2016 (actual)
- Primary completion
- 15 Aug 2018 (actual)
- Study completion
- 15 Sep 2018 (actual)
- First posted
- 7 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- Objectives: Evaluation of mesenchymal stem cell therapy effects on cellular and humoral immune responses in refractory rheumatoid arthritis (RA) patients.
- Design: This study has been performed as a phase 1 clinical trial.
- Setting and conduct: Autologous bone marrow derived mesenchymal stem cells were obtained by bone marrow aspiration and cultured in Minimum Essential Medium-Alpha (MEM-alpha) for 4 weeks in standard clean room and then transfused to RA patients intravenously.
- Participant's major eligibility criteria is as follows: Ten refractory rheumatoid arthritis patients who show resistance to non biological Disease-modifying antirheumatic drugs (DMARDs) after 6 to 12 months have been enrolled in this study.
- Intervention: A single dose of intravenous autologous bone marrow derived mesenchymal stem cells have been administered into patients with resistance to non-biological DMARDs.
- Main outcome measures (variables): Finding of mesenchymal stem cell therapy effects on the cellular and humoral immune responses and evaluation of the effect of chemokines in homing of immune cells following the intervention.
Detailed description
Refractory rheumatoid arthritis patients who met the inclusion/exclusion criteria have been selected. After signing informed consent form, autologous stem cells were obtained by bone marrow aspiration. Isolation and culture (3 to 4 weeks in MEM-alpha medium) of mesenchymal stem cells (MSCs) were performed in accredited good manufacturing practices (GMP) clean room. A panel of cluster of differentiation (CD) markers including CD105, CD166, CD44, CD45, CD90, and CD34 were checked for making sure about differentiation of cells into MSCs after 3-4 weeks of cell culture. Viability of MSCs was checked by Trypan blue testing and all of the cultivations were negative for bacterial contamination. A single dose of 1000000 to 2000000 mesenchymal stem cells/kg infused into patients intravenously. To prevent anaphylactic reactions, a single intravenous dose of hydrocortison (100 ml) and oral dimenhydrinate (10 ml) were administered before MSCs infusion into patients. The effects of mesenchymal stem cells on the cellular and humoral immune responses and also the role of chemokines in homing of immune cells were studied at time points 1, 6 and 12 months after intravenous administration of MSCs in refractory rheumatoid arthritis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Refractory rheumatoid arthritis patients | Experimental | Biological: Autologous mesenchymal stem cellsAutologous mesenchymal stem cells |
Who may qualify
- Ages
- 35 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (1 listed)
- Non-resistant RA patients to non-biological DMARDs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous mesenchymal stem cellsA single intravenous administration of autologous bone marrow derived mesenchymal stem cells(1000000 to 2000000 cells/Kg) | Biological | Refractory rheumatoid arthritis patients |
Primary outcome
Effect of mesenchymal stem cells therapy on the percentage of regulatory T cells
Time frame: At 0 and 6 months follow up
Percentage change in regulatory T cells from baseline which is analysed by fluorescence-activated cell sorting (FACS)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2019.
- Background: PubMed 27269294Alvaro-Gracia JM, Jover JA, Garcia-Vicuna R, Carreno L, Alonso A, Marsal S, Blanco F, Martinez-Taboada VM, Taylor P, Martin-Martin C, DelaRosa O, Tagarro I, Diaz-Gonzalez F. Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial. Ann Rheum Dis. 2017 Jan;76(1):196-202. doi: 10.1136/annrheumdis-2015-208918. Epub 2016 Jun 7.
- Background: PubMed 21837432Liang J, Li X, Zhang H, Wang D, Feng X, Wang H, Hua B, Liu B, Sun L. Allogeneic mesenchymal stem cells transplantation in patients with refractory RA. Clin Rheumatol. 2012 Jan;31(1):157-61. doi: 10.1007/s10067-011-1816-0. Epub 2011 Aug 12.
- Background: PubMed 23941289Wang L, Wang L, Cong X, Liu G, Zhou J, Bai B, Li Y, Bai W, Li M, Ji H, Zhu D, Wu M, Liu Y. Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy. Stem Cells Dev. 2013 Dec 15;22(24):3192-202. doi: 10.1089/scd.2013.0023. Epub 2013 Oct 4.
- Derived from this study: PubMed 37496411Rahimi Khorashad M, Ghoryani M, Gowhari Shabgah A, Shariati-Sarabi Z, Tavakkol Afshari J, Mohammadi M. The Effects of Mesenchymal Stem Cells on the Gene Expression of TGF-beta and IFN-gamma in Patients with Rheumatoid Arthritis. Iran J Allergy Asthma Immunol. 2023 Apr 30;22(2):183-189. doi: 10.18502/ijaai.v22i2.12679.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mojgan Mohammadi, Ph.D principal investigator
Mashhad University of Medical Sciences
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous mesenchymal stem cells in people with Rheumatoid Arthritis, run by Mashhad University of Medical Sciences.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of mesenchymal stem cells therapy on the percentage of regulatory T cells (time frame: At 0 and 6 months follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03333681, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2019.