Multiple SclerosisPhase 1/2STREAMSNCT01606215
Stem Cells in Rapidly Evolving Active Multiple Sclerosis
A Phase 1/2 study testing Mesenchymal stem cells in people with Multiple Sclerosis, run by Imperial College London at 1 site in United Kingdom.
Trial summary
This is a randomised, double-blind crossover study to study the effect of intravenous treatment with autologous (derived from the individuals themselves) mesenchymal stem cells (MSCs) in patients with multiple sclerosis (MS). 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?
- Mesenchymal stem cells
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2013to Aug 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with clinically and radiologically active multiple sclerosis as defined by:
- Diagnosis of MS:
- Relapsing remitting MS (RRMS): ≥ 1 moderate-severe relapse and ≥1 GEL in past 18 months or ≥ 1 moderate-severe relapse and ≥1 new T2 lesion in past 18 months.
- Secondary progressive MS (SPMS) with an increase of ≥ 1 EDSS point (if baseline EDSS ≤ 5) or 0.5 EDSS point (if baseline EDSS ≥ 5.5), in the previous 18 months and ≥ 1 GEL in past 18 months or ≥ 1 moderate-severe relapse and ≥1 new T2 lesion in past 18 months.
- Primary progressive MS (PPMS) patients with positive oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) and an increase of ≥ 1 EDSS point (if baseline EDSS is ≤ 5.0) or 0.5 EDSS point (if baseline EDSS is ≥ 5.5), or quantifiable, objective evidence of equivalent progression in the previous 18 months and ≥ 1 GEL in past 18 months or ≥ 1 new T2 lesion in past 18 months.
- Age 18 to 50 years.
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- Disease duration 2 to 10 years from diagnosis (inclusive).
- Expanded Disability Status Scale (EDSS) 2.0 to 6.5 at screening evaluation.
- ≥ 1 GEL on MRI within 6 months prior to harvesting.
- Adequate culture of a subject's MSCs and their release for clinical use.
Who cannot join
- RRMS without at least one severe relapse in the previous 18 months or without at least one GEL or one new T2 in the previous 18 months.
- SPMS without relapses and without new lesions (GEL or T2 positive) at MRI in the last 18 months.
- PPMS without positive CSF OCBs or without a GEL or new T2 lesion in the previous 18 months.
- No gadolinium enhancing lesion(s) in the 3 months prior to bone marrow harvesting.
- A previously ineligible patient who failed to meet the MRI requirements of the inclusion criteria will not be reviewed again even if further imaging, revealing ≥ 1 GEL, becomes available.
- Failure of bone marrow (BM) sample to generate MSCs suitable for clinical use within a specified time frame (4 weeks).
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- Treatment with any immunosuppressive therapy, including natalizumab and fingolimod, within the last 3 months.
- Treatment with interferon-beta or glatiramer acetate within the last 1 month.
- Treatment with alemtuzumab (campath-1H) within the last 2 years.
- Prior treatment with total lymphoid irradiation and autologous or allogeneic hematopoietic stem cell transplantation.
- Participation in clinical trials of any experimental drugs in the 6 months before study entry.
- Corticosteroid treatment in the last 30 days.
- Presence of any active or chronic infection.
- Previous history of a malignancy other than basal cell carcinoma of the skin and carcinoma in situ that has been in remission for more than one year.
- Severely limited life expectancy by any other co-morbid illness.
- Abnormal blood counts, a history of myelodysplasia or other cytopenia.
- Known pregnancy, positive urine pregnancy test at screening or risk or pregnancy (this includes patients who are unwilling to practice active contraception during the duration of the study).
- Contraindication to MRI including but not limited to intracranial aneurysm clips (except Sugita), history of intra-orbital metal fragments that have not been removed by an MD (as confirmed by orbital X-Ray), pacemaker and non-MRI compatible devices (e.g. heart valves, inner ear implants), history of claustrophobia or the inability of the subject to lie still on their back for a period of 1.5 hours in the MRI scanner.
- An estimated glomerular filtration rate (eGFR)< 60 mL/min/1.73m2 or history or presence of renal impairment (e.g. serum creatinine clearance less than 30ml/min).
- Inability to give written informed consent/comply with study procedures.
- Any significant organ dysfunction or co-morbidity that the Investigators consider would put the subject at unacceptable risk by participating in the study or that would interfere with the functional assessments.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, W12 0NN
About this study
This is a randomised, double-blind crossover study to study the effect of intravenous treatment with autologous (derived from the individuals themselves) mesenchymal stem cells (MSCs) in patients with multiple sclerosis (MS).
Read the detailed description
Current treatments for MS target the immune system and are not curative. There is much interest in MSCs as they have the potential to not only affect the immune system but may also promote repair. This study will use MSCs that are harvested from the bone marrow and grown for up to 52 days before being given back to the person from whom they were harvested. This avoids any chemotherapy so is therefore safer than other types of stem cells. In this crossover study, everyone will receive their own stem cells back but in half of the patients it will be delayed by 24 weeks.
The primary outcomes are to check that the procedure is safe and to measure any changes on the MRI at 24 weeks. Other more exploratory measures will try to assess effects on repair in the central nervous system (CNS).
- Conditions
- Multiple Sclerosis
- Being tested
- Mesenchymal stem cells, Placebo
- Keywords
- multiple sclerosis, mesenchymal stem cells, bone marrow, rapidly evolving
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal stem cellsDrug
Also called Mesenchymal stromal cells
1.0-2.0 million cells/kg body weight
PlaceboDrug
Also called Sham
Placebo
| Study group | Role | What they receive |
|---|---|---|
| mesenchymal stem cells | Experimental | 1-2 x106 MSCs/kg administered at Week 0 Receives: Drug: Mesenchymal stem cells |
| Placebo | Sham comparator | Suspension media administered at Week 0 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events Assessed by CTCAE v4.0
The number of adverse events before crossover in the stem cell treatment group compared to the placebo group over the first 24 weeks (please refer to period 1 of the participant flow).
Measured: 24 weeks from baseline
Number of GELs Newly Appearing at Weeks 4, 12 and 24 After MSC Therapy in the First 24 Weeks of Trial
Where GELs stands for gadolinium enhancing lesions and MSC for Mesenchymal Stem Cell.
This was to evaluate the efficacy of autologous mesenchymal stem cells in MS patients, quantified by the reduction in the number of new gadolinium-enhancing lesions counted on MRI scans over 24 weeks and the total number of GELs counted over months 1, 3 and 6 will be compared between treatment groups.
Measured: Up to 24 weeks
Secondary outcomes (5)
Number of Newly Appearing GELs Over Months 1, 3 and 6 Will be Compared Between Treatment Groups.
Number of gadolinium enhancing lesions identified over months 1, 3 and 6 will be compared between treatment groups - the treatment groups in this section relate to all 13 patients treated with MSCs (so patients in arm MSCs first, then placebo and 7 patients in placebo first, then MSCs) with 7 placebo patients (placebo first, then MSCs - the placebo group here ignores the 6 pts treated with MSCs first as we do not know whether there is any ongoing effect of MSCs beyond 24 weeks).
Measured: Months 1, 3 and 6
Comparison of Contrast Enhancing Lesions Between Treatment Periods Following Crossover
The number of contrast enhancing lesions counted over months 7, 9 and 12 (that is after cross-over).
Measured: Months 6-12
Combined Unique MRI Activity
To evaluate the efficacy of autologous mesenchymal stem cells in MS patients, quantified by the reduction in combined unique MRI activity on MRI scans over 24 weeks. The total number of such lesions counted over Weeks 4, 12 and 24 will be compared between treatment groups.
Combined Unique MRI activity defined as number of new T1w contrast-enhanced lesions plus number of new T2w lesions without contrast enhancement on T1w plus number of enlarging T2w lesions (>50% volume increase, no lesion fusion) without contrast enhancement on T1w.
Measured: Weeks 4, 12 and 24
Relapses
number of relapses in MSC treatment group vs. placebo group in the first 6 months
Measured: 6 months
Progression of Disability
EDSS at 6 months in both groups at Week 24: comparing 'MSCs first, then placebo' and 'Placebo first, then MSCs' at Week 24.
EDSS is a disability score. EDSS is an abbreviation for Expanded Disability Status Scale. Ranges from 0 (no disability) to 10 (death). A higher score indicates worsening disability.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2012 (estimated)
- Study startJan 2013
- Primary completionAug 2019
- Study completionAug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- 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
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paolo A Muraro, MD PhD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01606215
- Sponsor's protocol ID
- CRO1959
- Other IDs
- 13HH0228
- Acronym
- STREAMS
- Status last verified
- Jan 2025
- First submitted
- 21 May 2012
- Last updated
- 14 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 14 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stem Cells in Rapidly Evolving Active Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01606215
- Acronym / sponsor ID
- STREAMS / CRO1959
- Conditions
- Multiple Sclerosis
- Keywords
- multiple sclerosis, mesenchymal stem cells, bone marrow, rapidly evolving
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Jan 2013 (actual)
- Primary completion
- Aug 2019 (actual)
- Study completion
- Aug 2019 (actual)
- First posted
- 25 May 2012 (estimated)
- Results
- Posted 14 Jan 2025
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 randomised, double-blind crossover study to study the effect of intravenous treatment with autologous (derived from the individuals themselves) mesenchymal stem cells (MSCs) in patients with multiple sclerosis (MS).
Detailed description
Current treatments for MS target the immune system and are not curative. There is much interest in MSCs as they have the potential to not only affect the immune system but may also promote repair. This study will use MSCs that are harvested from the bone marrow and grown for up to 52 days before being given back to the person from whom they were harvested. This avoids any chemotherapy so is therefore safer than other types of stem cells. In this crossover study, everyone will receive their own stem cells back but in half of the patients it will be delayed by 24 weeks.
The primary outcomes are to check that the procedure is safe and to measure any changes on the MRI at 24 weeks. Other more exploratory measures will try to assess effects on repair in the central nervous system (CNS).
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 |
|---|---|---|
| mesenchymal stem cells | Experimental | Drug: Mesenchymal stem cells1-2 x106 MSCs/kg administered at Week 0 |
| Placebo | Sham comparator | Drug: PlaceboSuspension media administered at Week 0 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Diagnosis of MS:
- Age 18 to 50 years.
- Disease duration 2 to 10 years from diagnosis (inclusive).
- Expanded Disability Status Scale (EDSS) 2.0 to 6.5 at screening evaluation.
- ≥ 1 GEL on MRI within 6 months prior to harvesting.
Key exclusion criteria (21 listed)
- RRMS without at least one severe relapse in the previous 18 months or without at least one GEL or one new T2 in the previous 18 months.
- SPMS without relapses and without new lesions (GEL or T2 positive) at MRI in the last 18 months.
- PPMS without positive CSF OCBs or without a GEL or new T2 lesion in the previous 18 months.
- No gadolinium enhancing lesion(s) in the 3 months prior to bone marrow harvesting.
- A previously ineligible patient who failed to meet the MRI requirements of the inclusion criteria will not be reviewed again even if further imaging, revealing ≥ 1 GEL, becomes available.
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 |
|---|---|---|
| Mesenchymal stem cellsAlso: Mesenchymal stromal cells1.0-2.0 million cells/kg body weight | Drug | mesenchymal stem cells |
| PlaceboAlso: ShamPlacebo | Drug | Placebo |
Primary outcome
Number of Adverse Events Assessed by CTCAE v4.0
Time frame: 24 weeks from baseline
The number of adverse events before crossover in the stem cell treatment group compared to the placebo group over the first 24 weeks (please refer to period 1 of the participant flow).
Number of GELs Newly Appearing at Weeks 4, 12 and 24 After MSC Therapy in the First 24 Weeks of Trial
Time frame: Up to 24 weeks
Where GELs stands for gadolinium enhancing lesions and MSC for Mesenchymal Stem Cell. This was to evaluate the efficacy of autologous mesenchymal stem cells in MS patients, quantified by the reduction in the number of new gadolinium-enhancing lesions counted on MRI scans over 24 weeks and the total number of GELs counted over months 1, 3 and 6 will be compared between treatment groups.
5 secondary outcomes
Number of Newly Appearing GELs Over Months 1, 3 and 6 Will be Compared Between Treatment Groups.
Time frame: Months 1, 3 and 6
Comparison of Contrast Enhancing Lesions Between Treatment Periods Following Crossover
Time frame: Months 6-12
Combined Unique MRI Activity
Time frame: Weeks 4, 12 and 24
Relapses
Time frame: 6 months
Progression of Disability
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: 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.
- 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.
Paolo A Muraro, MD PhD principal investigator
Imperial College London
1 site 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 Mesenchymal stem cells in people with Multiple Sclerosis, run by Imperial College London at 1 site in United Kingdom.
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 10 inclusion and 21 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 14 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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?
Yes. Results are posted in the registry (first posted 14 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Adverse Events Assessed by CTCAE v4.0 (time frame: 24 weeks from baseline). The study lists 2 primary outcomes in all. 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 NCT01606215, 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 14 Jan 2025.