Multiple SclerosisSIAMMS-IINCT01932593
Repeat Infusion of Autologous Bone Marrow Cells in Multiple Sclerosis
A study testing Infusion of autologous bone marrow in people with Multiple Sclerosis, run by North Bristol NHS Trust at 1 site in United Kingdom.
Trial summary
There is no cure for Multiple Sclerosis (MS) and we are always looking at new ways to stop the disease process and/or promote repair. We hypothesise that autologous bone marrow cellular therapy in chronic MS offers durable benefit. Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Infusion of autologous bone marrow
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 31 Jan 2014to 20 Aug 2018
- Phase
- Interventional
- 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 25 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participation in the phase I safety and feasibility 'Study of Intravenous Autologous Marrow in Multiple Sclerosis' (SIAMMS) (REC reference number number 05/Q1704/137 Clin Pharmacol Ther. 2010 Jun;87(6):679-85)
Who cannot join
- pregnancy, breastfeeding or lactation
- bone marrow insufficiency
- history of lymphoproliferative disease or previous total lymphoid irradiation immune deficiency
- history of current or recent (<5 years) malignancy
- chronic or frequent drug-resistant bacterial infections or presence of active - infection requiring antimicrobial treatment
- frequent and/or serious viral infection
Show all 15Show fewer
- systemic or invasive fungal disease within 2 years of entry to study
- significant renal, hepatic, cardiac or respiratory dysfunction
- contraindication to anaesthesia
- bleeding or clotting diathesis
- current or recent (within preceding 12 months) immunomodulatory therapy other than corticosteroid therapy
- treatment with corticosteroids within the preceding 3 months
- radiation exposure in the past year other than chest / dental x-rays
- previous claustrophobia
- the presence of any implanted metal or other contraindication to MRI participation in another experimental study or treatment within previous 24 months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Repeat Infusion of Autologous Bone Marrow Cells in Multiple Sclerosis (SIAMMS-II)
There is no cure for Multiple Sclerosis (MS) and we are always looking at new ways to stop the disease process and/or promote repair.
We hypothesise that autologous bone marrow cellular therapy in chronic MS offers durable benefit.
Read more
The purpose of this study is to test the safety of repeated bone marrow stem cell infusion in patients with MS. We want to find out what effects, good and/or bad, it has on you and your disability.
You have previously participated in a safety study of bone marrow stem cell infusion in patients with MS. The results raised the possibility of some early partial repair; measurements of the speed of neurological impulses in the brain and spinal cord improved. The current study seeks to determine whether those benefits have persisted and whether they can be repeated or enhanced by repeating the procedure.
Read the detailed description
On the background of our own and others' experimental BM stem cell studies, we recently completed a phase 1 feasibility/safety trial of BM cell therapy in 6 patients with longstanding progressive MS (www.nature.com/clpt/journal/v87/n6/full/clpt201044a.html). Safety was confirmed, and intensive serial neurophysiological tests showed statistically significant improvements at 12 months. While highly preliminary and entirely uncontrolled, these results at least raise the possibility of a beneficial effect within the damaged central nervous system (CNS). A phase 2 clinical trial to formally assess efficacy of intravenous infusion of autologous bone marrow cells in progressive MS will commence in the near future (ACTiMuS trial). This trial comprises a programme of translational and clinical stem cell research, aiming (1) to continue translation with a phase two controlled trial of autologous bone marrow cells (BMCs) in chronic MS; and (2) to explore in parallel the potential mechanisms of action by studying BM cells from treated patients and controls, aiming to establish which BM sub-population(s) contribute(s) to efficacy, and which reparative mechanism(s) are important.
It is not known whether repeated infusion of autologous bone marrow offers additional benefit or how long improvements might be expected to last. The current proposal seeks to explore whether the neurophysiological improvements observed in the phase I study persist several years after the initial single infusion and whether these can be either replicated or augmented by an additional infusion of autologous bone marrow cells.
Hypothesis and aims
We hypothesise that intravenously-delivered autologous bone marrow cellular therapy (BMCT) in chronic MS offers significant benefit. We hypothesize also that the mechanisms are multiple, and include immunomodulation and reparative and/or neuroprotective effects within the CNS; and are offered by one or more BM stem cell sub-populations, jointly contributing to the therapeutic impact. Exploring and understanding these mechanisms, and the biology of the cells responsible, will allow the development of more effective reparative cell therapy in MS.
The current study seeks to examine whether the observed improvements noted in conduction times in central nervous system pathways in the phase I 'Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)' persist several years following the initial single infusion and whether these can be either replicated or augmented by an additional infusion of autologous bone marrow cells and analysis of research samples will be performed as per samples included in the concurrent phase 2 clinical trial 'Assessment of bone marrow-derived cellular therapy in progressive multiple sclerosis (ACTiMuS)' (REC 12/SW/0358, ISRCTN27232902, NCT01815632).
- Conditions
- Multiple Sclerosis
- Being tested
- Infusion of autologous bone marrow
- Keywords
- multiple sclerosis, bone marrow, stem cell therapy
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infusion of autologous bone marrowProcedure or surgery
Bone marrow harvest under general anaesthetic and intravenous infusion of filtered but otherwise unselected autologous bone marrow
| Study group | Role | What they receive |
|---|---|---|
| Infusion of autologous bone marrow | Experimental | Bone marrow harvest under general anaesthetic and intravenous infusion of filtered but otherwise unselected autologous bone marrow Receives: Procedure: Infusion of autologous bone marrow |
| Placebo | Placebo comparator | Not described Receives: Procedure: Infusion of autologous bone marrow |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Number of adverse events
Measured: 1 year post-infusion of autologous bone marrow
Secondary outcomes (5)
Global evoked potential
The 'global evoked potential (GEP)' has been developed as a tool that, by combining multimodal evoked potential recordings to a single score, may be used to monitor the evolution of MS in individual patients, and as a surrogate end point in clinical trials.
Measured: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
MRI brain
MRI brain scan
Measured: Baseline and 6 months post-infusion of autologous bone marrow
Expanded disability status scale (EDSS)
Expanded disability status scale - clinical scale of disability used in MS trials
Measured: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
Multiple sclerosis functional composite (MSFC)
The MSFC is a three-part quantitative assessment of disability and includes a timed walk, the nine-hole peg test and the Paced Auditory Serial Addition Test (PASAT).
Measured: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
Multiple sclerosis impact scale (MSIS-29)
Self-reporting questionnaire re impact of MS
Measured: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2013 (estimated)
- Study start31 Jan 2014
- Primary completion1 Sep 2017
- Study completion20 Aug 2018
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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- autologous bone marrow cells
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- North Bristol NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- Sir Halley Stewart Trust
- Responsible party
- Sponsor
- Investigators
- Neil J Scolding, PhD FRCP, Principal investigator, North Bristol NHS Trust and University of Bristol
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01932593
- Sponsor's protocol ID
- SIAMMS-II
- Acronym
- SIAMMS-II
- Status last verified
- Aug 2018
- First submitted
- 13 Aug 2013
- Last updated
- 23 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Rice CM, Marks DI, Walsh P, Kane NM, Guttridge MG, Redondo J, Sarkar P, Owen D, Wilkins A, Scolding NJ. Repeat infusion of autologous bone marrow cells in multiple sclerosis: protocol for a phase I extension study (SIAMMS-II). BMJ Open. 2015 Sep 11;5(9):e009090. doi: 10.1136/bmjopen-2015-009090.
PubMed 26363342
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repeat Infusion of Autologous Bone Marrow Cells in Multiple Sclerosis (SIAMMS-II)
- ClinicalTrials.gov ID
- NCT01932593
- Acronym / sponsor ID
- SIAMMS-II / SIAMMS-II
- Conditions
- Multiple Sclerosis
- Keywords
- multiple sclerosis, bone marrow, stem cell therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- North Bristol NHS TrustUniversity, hospital or other
- Collaborators
- Sir Halley Stewart Trust
- Study start
- 31 Jan 2014 (actual)
- Primary completion
- 1 Sep 2017 (actual)
- Study completion
- 20 Aug 2018 (actual)
- First posted
- 30 Aug 2013 (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.
There is no cure for Multiple Sclerosis (MS) and we are always looking at new ways to stop the disease process and/or promote repair.
We hypothesise that autologous bone marrow cellular therapy in chronic MS offers durable benefit.
The purpose of this study is to test the safety of repeated bone marrow stem cell infusion in patients with MS. We want to find out what effects, good and/or bad, it has on you and your disability.
You have previously participated in a safety study of bone marrow stem cell infusion in patients with MS. The results raised the possibility of some early partial repair; measurements of the speed of neurological impulses in the brain and spinal cord improved. The current study seeks to determine whether those benefits have persisted and whether they can be repeated or enhanced by repeating the procedure.
Detailed description
On the background of our own and others' experimental BM stem cell studies, we recently completed a phase 1 feasibility/safety trial of BM cell therapy in 6 patients with longstanding progressive MS (www.nature.com/clpt/journal/v87/n6/full/clpt201044a.html). Safety was confirmed, and intensive serial neurophysiological tests showed statistically significant improvements at 12 months. While highly preliminary and entirely uncontrolled, these results at least raise the possibility of a beneficial effect within the damaged central nervous system (CNS). A phase 2 clinical trial to formally assess efficacy of intravenous infusion of autologous bone marrow cells in progressive MS will commence in the near future (ACTiMuS trial). This trial comprises a programme of translational and clinical stem cell research, aiming (1) to continue translation with a phase two controlled trial of autologous bone marrow cells (BMCs) in chronic MS; and (2) to explore in parallel the potential mechanisms of action by studying BM cells from treated patients and controls, aiming to establish which BM sub-population(s) contribute(s) to efficacy, and which reparative mechanism(s) are important.
It is not known whether repeated infusion of autologous bone marrow offers additional benefit or how long improvements might be expected to last. The current proposal seeks to explore whether the neurophysiological improvements observed in the phase I study persist several years after the initial single infusion and whether these can be either replicated or augmented by an additional infusion of autologous bone marrow cells.
Hypothesis and aims
We hypothesise that intravenously-delivered autologous bone marrow cellular therapy (BMCT) in chronic MS offers significant benefit. We hypothesize also that the mechanisms are multiple, and include immunomodulation and reparative and/or neuroprotective effects within the CNS; and are offered by one or more BM stem cell sub-populations, jointly contributing to the therapeutic impact. Exploring and understanding these mechanisms, and the biology of the cells responsible, will allow the development of more effective reparative cell therapy in MS.
The current study seeks to examine whether the observed improvements noted in conduction times in central nervous system pathways in the phase I 'Study of Intravenous Autologous Marrow in Multiple Sclerosis (SIAMMS)' persist several years following the initial single infusion and whether these can be either replicated or augmented by an additional infusion of autologous bone marrow cells and analysis of research samples will be performed as per samples included in the concurrent phase 2 clinical trial 'Assessment of bone marrow-derived cellular therapy in progressive multiple sclerosis (ACTiMuS)' (REC 12/SW/0358, ISRCTN27232902, NCT01815632).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- autologous bone marrow cells
| Arm | Type | Receives |
|---|---|---|
| Infusion of autologous bone marrow | Experimental | Procedure: Infusion of autologous bone marrowBone marrow harvest under general anaesthetic and intravenous infusion of filtered but otherwise unselected autologous bone marrow |
| Placebo | Placebo comparator | Procedure: Infusion of autologous bone marrow |
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Participation in the phase I safety and feasibility 'Study of Intravenous Autologous Marrow in Multiple Sclerosis' (SIAMMS) (REC reference number number 05/Q1704/137 Clin Pharmacol Ther. 2010 Jun;87(6):679-85)
Key exclusion criteria (15 listed)
- pregnancy, breastfeeding or lactation
- bone marrow insufficiency
- history of lymphoproliferative disease or previous total lymphoid irradiation immune deficiency
- history of current or recent (<5 years) malignancy
- chronic or frequent drug-resistant bacterial infections or presence of active - infection requiring antimicrobial treatment
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 |
|---|---|---|
| Infusion of autologous bone marrowBone marrow harvest under general anaesthetic and intravenous infusion of filtered but otherwise unselected autologous bone marrow | Procedure or surgery | Infusion of autologous bone marrow, Placebo |
Primary outcome
Adverse events
Time frame: 1 year post-infusion of autologous bone marrow
Number of adverse events
5 secondary outcomes
Global evoked potential
Time frame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
MRI brain
Time frame: Baseline and 6 months post-infusion of autologous bone marrow
Expanded disability status scale (EDSS)
Time frame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
Multiple sclerosis functional composite (MSFC)
Time frame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
Multiple sclerosis impact scale (MSIS-29)
Time frame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
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 23 Aug 2018.
- Derived from this study: PubMed 26363342Rice CM, Marks DI, Walsh P, Kane NM, Guttridge MG, Redondo J, Sarkar P, Owen D, Wilkins A, Scolding NJ. Repeat infusion of autologous bone marrow cells in multiple sclerosis: protocol for a phase I extension study (SIAMMS-II). BMJ Open. 2015 Sep 11;5(9):e009090. doi: 10.1136/bmjopen-2015-009090.
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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.
Neil J Scolding, PhD FRCP principal investigator
North Bristol NHS Trust and University of Bristol
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Infusion of autologous bone marrow in people with Multiple Sclerosis, run by North Bristol NHS Trust 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 1 inclusion and 15 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 23 Aug 2018. 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.
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?
Adverse events (time frame: 1 year post-infusion of autologous bone marrow). 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 NCT01932593, 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 23 Aug 2018.