Multiple SclerosisPhase 1/2NCT01745783
Mesenchymal Cells From Autologous Bone Marrow, Administered Intravenously in Patients Diagnosed With Multiple Sclerosis
A Phase 1/2 study testing Bone marrow mesenchymal stem cells autologous in people with Multiple Sclerosis, run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 3 sites in Spain.
Trial summary
This is a phase I / II for the evaluation of the safety and feasibility of intravenous infusion of mesenchymal cells from autologous bone marrow in patients with Multiple Sclerosis. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Bone marrow mesenchymal stem cells autologous
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 3 sitesSpain
- Study dates
- Jan 2013to 30 Jun 2020
- Phase
- Phase 1/2
- 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 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 1. Patients diagnosed with MS in their inflammatory forms :
- Course outbreaks ( relapsing- remitting ) , who have not responded to at least one year of treatment with one or more of the approved therapies (beta - interferon, glatiramer acetate, natalizumab , mitoxantrone, fingolimod ) , confirmed by one or more of the following criteria:
- ( ii ) At least one clinically documented outbreak in the past 12 months. ( iii ) At least two clinically documented outbreaks in the last 24 months ( iv ) At least one lesion with gadolinium on MRI performed in the last 12 months.
- b . Secondary progressive forms that have not responded to at least one year of treatment with one or more of the approved therapies ( interferon beta , glatiramer acetate, natalizumab , mitoxantrone, fingolimod ) . That meet the following criteria:
- ( i ) Increase of 1 point or more if baseline EDSS score is less than or equal to 5.0 , or 0.5 point increase if the baseline score is greater than or equal to 5.5, in the last 12 months.
- ( ii ) at least one clinically documented outbreak or at least one lesion with gadolinium on MRI within the last 12 months.
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- c . Primary progressive forms that meet the following three criteria:
- ( i ) Increase of 1 point or more if baseline EDSS score is less than or equal to 5.0 , or 0.5 point increase if the baseline score is greater than or equal to 5.5, in the last 12 months.
- ( ii ) At least 1 lesion with gadolinium on MRI within the last 12 months. ( iii ) oligoclonal bands in cerebrospinal fluid (CSF) .
- 2 . Normal laboratory parameters , defined by:
- Leukocytes ≥ 3000
- Neutrophils ≥ 1500
- Platelets ≥ 100,000
- Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) ≤ 2.5 standard range institution
- Creatinine ≤ 2.5 mg / dl
- 3 . Patients of both sexes aged between 18 and 50.
- 4 . Disease duration ≥ 2 years and ≤ 10 years.
- 5 . EDSS (Expanded Disability Status Scale) between 3.0 and 6.5 points.
- 6. Patients give their informed consent for participation in the clinical trial consent.
- 7. Women of childbearing potential must have negative results on a pregnancy test at the time of inclusion in the study and agree to use a medically approved method of contraception while on study
Who cannot join
- Any active or chronic infection, including Hepatitis B virus (HBV), Hepatitis C virus (HCV) or HIV .
- Immunosuppressive therapy in the 3 months prior to randomization (including natalizumab and fingolimod ).
- Treatment with interferon beta or glatiramer acetate in the 30 days prior to randomization .
- Corticosteroid therapy in the 30 days prior to randomization.
- Time since last exceeding 60 days prior to randomization outbreak.
- History of malignancy ( basal cell carcinoma of skin and carcinoma in situ are excluded in remission for over a year).
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- Life expectancy severely limited by other co - morbidities.
- Previous history of myelodysplasia or hematological disease , or clinically relevant changes currently in the leukocyte count.
- Pregnancy / risk of pregnancy (including refusal to use contraception)
- Renal failure (eGFR <60 mL/min/1.37m2)
- Inability to undergo MRI scans
- Inability to give written informed consent.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
University Hospital Reina Sofia
Córdoba, 14004
University Regional Hospital Carlos Haya
Málaga, 29010
University Hospital Virgen Macarena
Seville, 41009
About this study
Official title: Clinical Trial Phase I / II Multicenter, Randomized, Crossover, Double-blind Evaluation of the Safety and Feasibility of Systemic Therapy With Mesenchymal Cells Derived From Autologous Bone Marrow in Patients With Multiple Sclerosis
This is a phase I / II for the evaluation of the safety and feasibility of intravenous infusion of mesenchymal cells from autologous bone marrow in patients with Multiple Sclerosis.
Intravenous administration of autologous mesenchymal cells of bone marrow is feasible and safe and can be effective in treating patients suffering from multiple sclerosis.
Read the detailed description
The study population will consist of a total of 30 patients diagnosed with multiple sclerosis, who meet all inclusion criteria and none of the exclusion set and express their agreement to participate in the study by signing the informed consent of those whose results can be clinically evaluable.
Selected patients who consent will be enrolled in the trial and randomized to one of the following groups:
- Group 1 receiving a single intravenous administration of cellular product on Day 0 and placebo infusion on day + 180.
- Group 2 receiving a placebo infusion on day 0 and a single cell product administration on day +180.
Randomization will be 1:1, so that 15 patients will receive the cellular product on Day 0 (Group 1) and 15 patients on day +180 (group 2), always maintaining at all times the double-blind status of the test (patients and researchers).
The bone marrow will be extract from all patients immediately after inclusion in the study, under local anesthesia with sedation. For patients in group 1 autologous mesenchymal cells will be obtained from the bone marrow and infuse immediately after the time necessary for their production. For patients in group 2, bone marrow cells will be frozen for later procedure of mesenchymal cells and their infusion after six months.
Patients will be evaluated by clinical, radiological, and electrophysiological as well as detailed in section 8 corresponding to Development Test and Evaluation of Response.
It is estimated that the inclusion period is approximately 12-18 months, and each patient tracking another twelve months. Therefore the total duration of the study will be about 24 to 30 months from the inclusion of the first patient to completion follow-up period of the last patient included.
Study objectives:
- Main objectives: 1. To evaluate the safety of intravenous infusion of autologous bone marrow mesenchymal cells in multiple sclerosis patients diagnosed by evaluating complications and adverse effects of the therapy itself and study procedures.
- Assessing the difference in the number of lesions on magnetic resonance image with gadolinium, between the groups undergoing treatment at weeks 4, 12 and 24.
- Secondary objectives: 1. To evaluate the feasibility and efficacy of the indication of the treatment by analysis comparative results and exploratory clinical variables of patients at baseline (pretreatment) and at 6 and 12 months follow-up.
- Compare the results of safety, feasibility and efficacy between the administration initial cell therapy treatment (day 0) and that delayed (day +180).
- Evaluating the immunomodulatory effect of treatment by quantifying cell subsets and cytokines, functional analysis of the immune response. Cerebrospinal fluid metabolomic profile of gene expression of the cells present in blood and cerebrospinal fluid, with the aim of identifying new biomarkers with diagnosis of interest, prognosis or monitoring, and potential therapeutic targets that can be derived from it.
- Providing our results to the study proposed by the International Mesenchymal Stem Cell Transplant Study Group under whose directives will be performed the test.
- Conditions
- Multiple Sclerosis
- Being tested
- Bone marrow mesenchymal stem cells autologous, Placebo comparator
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bone marrow mesenchymal stem cells autologousOther
Infusion of mesenchymal cells from autologous bone marrow in a dose of 1-2x106 cells / kg
Placebo comparatorOther
Lactated Ringer's solution, 2.5% glucose and 1% human albumin.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Receive a single IV administration of cellular product (Bone marrow mesenchymal stem cells autologous) on Day 0 and placebo infusion on day + 180.
Dose: 1-2x10^6 cells/Kg Receives: Other: Bone marrow mesenchymal stem cells autologous |
| Placebo Comparator | Placebo comparator | Receive a placebo infusion on day 0 and a single administration cellular product on day +180. Dose: 1-2x10^6 cells/Kg Receives: Other: Placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absence of unexpected serious adverse reactions as a measure of safety and reduction in number and volumes of the lesions on magnetic resonance image
Measured: 12 months
Secondary outcomes (1)
Differences the results obtained in the two groups of patients due to determined parameters.
Secondary variables consist of differences the results obtained in the two groups of patients (treated versus treated at day 0 to day +180) at 12 month follow-up with respect to the following parameters:
- Disease activity on magnetic resonance (used one single combined index activity consisting of the presence of new or enlarged T2 or new or recurrence of injury).
- Changes in Expanded Disability Status Scale (EDSS).
- Changes Multiple Sclerosis Functional Composite (MSFC).
- Changes in quality of life scales
- Outbreaks: number and proportion of time off outbreaks.
- Disease-free patients (no sprouts, no progression and no activity in the RM).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2012 (estimated)
- Study startJan 2013
- Primary completion30 Jun 2020
- Study completion30 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
- Sponsor type
- University, hospital or other
- Collaborators
- Iniciativa Andaluza en Terapias Avanzadas
- Responsible party
- Sponsor
- Investigators
- Guillermo Izquierdo, MD, Principal investigator, Section Chief of Neurology, University Hospital Virgen Macarena, SpainEduardo Agüera, MD, Principal investigator, Section of Neurology, University Hospital Reina Sofía, SpainVictoria Fernández, MD, Principal investigator, Section of Neurophysiology, University Regional Hospital Carlos Haya, SpainInmaculada Concepción Herrera, MD, Study chair, Technical Director of the Cell Therapy Unit, University Hospital Reina Sofia, Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01745783
- Sponsor's protocol ID
- CeTMMo/EM/2010
- Other IDs
- 2010-023368-42
- Status last verified
- Apr 2022
- First submitted
- 3 Dec 2012
- Last updated
- 6 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Uccelli A, Laroni A, Brundin L, Clanet M, Fernandez O, Nabavi SM, Muraro PA, Oliveri RS, Radue EW, Sellner J, Soelberg Sorensen P, Sormani MP, Wuerfel JT, Battaglia MA, Freedman MS; MESEMS study group. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis. Trials. 2019 May 9;20(1):263. doi: 10.1186/s13063-019-3346-z.
PubMed 31072380
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial Phase I / II Multicenter, Randomized, Crossover, Double-blind Evaluation of the Safety and Feasibility of Systemic Therapy With Mesenchymal Cells Derived From Autologous Bone Marrow in Patients With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01745783
- Acronym / sponsor ID
- CeTMMo/EM/2010
- Conditions
- Multiple Sclerosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y SaludUniversity, hospital or other
- Collaborators
- Iniciativa Andaluza en Terapias Avanzadas
- Study start
- Jan 2013 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 10 Dec 2012 (estimated)
- 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.
This is a phase I / II for the evaluation of the safety and feasibility of intravenous infusion of mesenchymal cells from autologous bone marrow in patients with Multiple Sclerosis.
Intravenous administration of autologous mesenchymal cells of bone marrow is feasible and safe and can be effective in treating patients suffering from multiple sclerosis.
Detailed description
The study population will consist of a total of 30 patients diagnosed with multiple sclerosis, who meet all inclusion criteria and none of the exclusion set and express their agreement to participate in the study by signing the informed consent of those whose results can be clinically evaluable.
Selected patients who consent will be enrolled in the trial and randomized to one of the following groups:
- Group 1 receiving a single intravenous administration of cellular product on Day 0 and placebo infusion on day + 180.
- Group 2 receiving a placebo infusion on day 0 and a single cell product administration on day +180.
Randomization will be 1:1, so that 15 patients will receive the cellular product on Day 0 (Group 1) and 15 patients on day +180 (group 2), always maintaining at all times the double-blind status of the test (patients and researchers).
The bone marrow will be extract from all patients immediately after inclusion in the study, under local anesthesia with sedation. For patients in group 1 autologous mesenchymal cells will be obtained from the bone marrow and infuse immediately after the time necessary for their production. For patients in group 2, bone marrow cells will be frozen for later procedure of mesenchymal cells and their infusion after six months.
Patients will be evaluated by clinical, radiological, and electrophysiological as well as detailed in section 8 corresponding to Development Test and Evaluation of Response.
It is estimated that the inclusion period is approximately 12-18 months, and each patient tracking another twelve months. Therefore the total duration of the study will be about 24 to 30 months from the inclusion of the first patient to completion follow-up period of the last patient included.
Study objectives:
- Main objectives: 1. To evaluate the safety of intravenous infusion of autologous bone marrow mesenchymal cells in multiple sclerosis patients diagnosed by evaluating complications and adverse effects of the therapy itself and study procedures.
- Assessing the difference in the number of lesions on magnetic resonance image with gadolinium, between the groups undergoing treatment at weeks 4, 12 and 24.
- Secondary objectives: 1. To evaluate the feasibility and efficacy of the indication of the treatment by analysis comparative results and exploratory clinical variables of patients at baseline (pretreatment) and at 6 and 12 months follow-up.
- Compare the results of safety, feasibility and efficacy between the administration initial cell therapy treatment (day 0) and that delayed (day +180).
- Evaluating the immunomodulatory effect of treatment by quantifying cell subsets and cytokines, functional analysis of the immune response. Cerebrospinal fluid metabolomic profile of gene expression of the cells present in blood and cerebrospinal fluid, with the aim of identifying new biomarkers with diagnosis of interest, prognosis or monitoring, and potential therapeutic targets that can be derived from it.
- Providing our results to the study proposed by the International Mesenchymal Stem Cell Transplant Study Group under whose directives will be performed the test.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Other: Bone marrow mesenchymal stem cells autologousReceive a single IV administration of cellular product (Bone marrow mesenchymal stem cells autologous) on Day 0 and placebo infusion on day + 180. Dose: 1-2x10^6 cells/Kg |
| Placebo Comparator | Placebo comparator | Other: Placebo comparatorReceive a placebo infusion on day 0 and a single administration cellular product on day +180. Dose: 1-2x10^6 cells/Kg |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (20 listed)
- Course outbreaks ( relapsing- remitting ) , who have not responded to at least one year of treatment with one or more of the approved therapies (beta - interferon, glatiramer acetate, natalizumab , mitoxantrone, fingolimod ) , confirmed by one or more of the following criteria:
- ( ii ) At least one clinically documented outbreak in the past 12 months. ( iii ) At least two clinically documented outbreaks in the last 24 months ( iv ) At least one lesion with gadolinium on MRI performed in the last 12 months.
- b . Secondary progressive forms that have not responded to at least one year of treatment with one or more of the approved therapies ( interferon beta , glatiramer acetate, natalizumab , mitoxantrone, fingolimod ) . That meet the following criteria:
- ( i ) Increase of 1 point or more if baseline EDSS score is less than or equal to 5.0 , or 0.5 point increase if the baseline score is greater than or equal to 5.5, in the last 12 months.
- ( ii ) at least one clinically documented outbreak or at least one lesion with gadolinium on MRI within the last 12 months.
Key exclusion criteria (12 listed)
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 |
|---|---|---|
| Bone marrow mesenchymal stem cells autologousInfusion of mesenchymal cells from autologous bone marrow in a dose of 1-2x106 cells / kg | Other | Experimental |
| Placebo comparatorLactated Ringer's solution, 2.5% glucose and 1% human albumin. | Other | Placebo Comparator |
Primary outcome
Absence of unexpected serious adverse reactions as a measure of safety and reduction in number and volumes of the lesions on magnetic resonance image
Time frame: 12 months
1 secondary outcome
Differences the results obtained in the two groups of patients due to determined parameters.
Time frame: 12 months
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 6 Apr 2022.
- Derived from this study: PubMed 31072380Uccelli A, Laroni A, Brundin L, Clanet M, Fernandez O, Nabavi SM, Muraro PA, Oliveri RS, Radue EW, Sellner J, Soelberg Sorensen P, Sormani MP, Wuerfel JT, Battaglia MA, Freedman MS; MESEMS study group. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis. Trials. 2019 May 9;20(1):263. doi: 10.1186/s13063-019-3346-z.
- Andalusian Molecular Biology and Regenerative Medicine CentreLink provided by the sponsor.
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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.
Guillermo Izquierdo, MD principal investigator
Section Chief of Neurology, University Hospital Virgen Macarena, Spain
Eduardo Agüera, MD principal investigator
Section of Neurology, University Hospital Reina Sofía, Spain
Victoria Fernández, MD principal investigator
Section of Neurophysiology, University Regional Hospital Carlos Haya, Spain
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bone marrow mesenchymal stem cells autologous in people with Multiple Sclerosis, run by Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud at 3 sites in Spain.
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 20 inclusion and 12 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 6 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Absence of unexpected serious adverse reactions as a measure of safety and reduction in number and volumes of the lesions on magnetic resonance image (time frame: 12 months). 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 NCT01745783, which also lists 1 linked publication.
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 6 Apr 2022.