Ignite Creation Date:
2025-12-24 @ 9:34 PM
Ignite Modification Date:
2026-01-01 @ 8:03 AM
Study NCT ID:
NCT01815632
Status:
UNKNOWN
Last Update Posted:
2018-06-27
First Post:
2013-03-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Assessment of Bone Marrow-derived Cellular Therapy in Progressive Multiple Sclerosis (ACTiMuS)
Sponsor:
North Bristol NHS Trust
Organization:
Study Overview
Official Title:
Assessment of Bone Marrow-derived Cellular Therapy in Progressive Multiple Sclerosis (ACTiMuS)
Status:
UNKNOWN
Status Verified Date:
2018-06
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ACTiMuS
Brief Summary:
Multiple sclerosis - MS - affects 1.3m people worldwide, costing the European Union economy €9 billion/year, through both direct and indirect consequences of progressive disability. Despite the usual relapsing-remitting presentation, over 80% of patients develop progressive disability; 40% require a wheelchair within 10 years of diagnosis. At present, there are no treatments that reverse, halt or even slow progressive disability in MS.
The investigators recently completed one of the first feasibility/safety trials in the world of reparative bone marrow cell therapy in 6 patients with longstanding MS (www.nature.com/clpt/journal/v87/n6/full/clpt201044a.html). Safety was confirmed, and intensive repeated tests on the patients measuring nerve conduction in various pathways in the brain and in the spinal cord showed statistically significant improvements at 12 months in every patient. While highly preliminary and involving only a very small number of patients, these results at least raise the possibility of a significant (though very partial) underlying repair effect within the damaged nervous system.
The investigators believe this urgently requires further testing - both to accelerate benefit for patients, and to begin improving therapeutic efficacy. The investigators therefore propose a programme of translational and clinical stem cell research, aiming (1) to continue translation with a phase two controlled trial of bone marrow cells in patients with longstanding MS; and (2) to explore in parallel the potential mechanisms of action, by studying bone marrow cells from treated patients and control subjects, aiming to establish which of the various relevant bone marrow subpopulations contribute to efficacy, and which particular reparative mechanism(s) are important. The investigators hope these studies will not only confirm the therapeutic benefit of this approach, but also provide the basis for improving the magnitude and impact of this novel and exciting treatment modality.
The investigators recently completed one of the first feasibility/safety trials in the world of reparative bone marrow cell therapy in 6 patients with longstanding MS (www.nature.com/clpt/journal/v87/n6/full/clpt201044a.html). Safety was confirmed, and intensive repeated tests on the patients measuring nerve conduction in various pathways in the brain and in the spinal cord showed statistically significant improvements at 12 months in every patient. While highly preliminary and involving only a very small number of patients, these results at least raise the possibility of a significant (though very partial) underlying repair effect within the damaged nervous system.
The investigators believe this urgently requires further testing - both to accelerate benefit for patients, and to begin improving therapeutic efficacy. The investigators therefore propose a programme of translational and clinical stem cell research, aiming (1) to continue translation with a phase two controlled trial of bone marrow cells in patients with longstanding MS; and (2) to explore in parallel the potential mechanisms of action, by studying bone marrow cells from treated patients and control subjects, aiming to establish which of the various relevant bone marrow subpopulations contribute to efficacy, and which particular reparative mechanism(s) are important. The investigators hope these studies will not only confirm the therapeutic benefit of this approach, but also provide the basis for improving the magnitude and impact of this novel and exciting treatment modality.
Detailed Description:
The primary objective is to determine whether autologous bone marrow (BM) (ie taken from the patients themselves rather than from a BM donor) cell therapy is truly beneficial in chronic multiple sclerosis - as our small, uncontrolled phase 1 trial suggested (www.nature.com/clpt/journal/v87/n6/full/clpt201044a.html).
The investigators also aim to answer the following questions:
1. Do BM mesenchymal stem cells from patients with MS differ in the range or extent of reparative and neuroprotective properties from those from control individuals?
2. What reparative and neuroprotective properties do BM stem cell subpopulations other than mesenchymal stem cells possess, and do these differ between MS patients and controls?
3. Can BM stem cell subpopulations be isolated from blood samples from MS patients following treatment, and, if so, for how long?
Bone marrow contains stem cells capable of replacing all the cells in the blood. Recently, bone marrow has been found to contain cells capable of replacing cells in tissues and organs other than blood. In addition, infusion of bone marrow-derived cells has been shown to have significant effects on the immune system and to promote the survival of central nervous system cells under toxic conditions. These properties are of considerable interest to those working to develop cell-based therapies for neurodegenerative disease.
The potential of such cells to aid repair in multiple sclerosis (MS) has been examined in experimental models of MS. Myelin is the substance that insulates neurons within the central nervous system and is attacked in MS. Infusion of adult bone marrow cells into a vein aids myelin repair (remyelination) in these models of MS. Recently, the investigators performed a small pilot study to examine the effects of harvesting bone marrow from MS patients and infusing this back into each patient's vein. This was well tolerated and no significant adverse events were encountered. Electrophysiological studies appeared to show some improvement but, given the small numbers of participants in the phase 1 trial, no definitive conclusion can be made regarding this.
The current study seeks to address the question of whether genuine improvements in neurophysiological tests are seen in MS patients with progressive disease following infusion of bone marrow.
A prospective, randomised, double-blind, placebo-controlled, stepped wedge design will be employed at a single centre (Bristol, UK). Eighty patients with progressive MS will be recruited; 60 will have secondary progressive disease (SPMS) but a subset (n=20) will have primary progressive disease (PPMS). Participants will be randomised to either early (immediate) or late (1 year) intravenous infusion of autologous, unfractionated bone marrow. The placebo intervention is infusion of autologous blood. The primary outcome measure is global evoked potential derived from multimodal evoked potentials. Secondary outcome measures include adverse event reporting, clinical (EDSS and MSFC) and self-assessment (MSIS-29) rating scales, optical coherence tomography (OCT) as well as brain and spine MRI. Participants will be followed up for a further year following the final intervention. Outcomes will be analyzed on an intention-to-treat basis.
The investigators also aim to answer the following questions:
1. Do BM mesenchymal stem cells from patients with MS differ in the range or extent of reparative and neuroprotective properties from those from control individuals?
2. What reparative and neuroprotective properties do BM stem cell subpopulations other than mesenchymal stem cells possess, and do these differ between MS patients and controls?
3. Can BM stem cell subpopulations be isolated from blood samples from MS patients following treatment, and, if so, for how long?
Bone marrow contains stem cells capable of replacing all the cells in the blood. Recently, bone marrow has been found to contain cells capable of replacing cells in tissues and organs other than blood. In addition, infusion of bone marrow-derived cells has been shown to have significant effects on the immune system and to promote the survival of central nervous system cells under toxic conditions. These properties are of considerable interest to those working to develop cell-based therapies for neurodegenerative disease.
The potential of such cells to aid repair in multiple sclerosis (MS) has been examined in experimental models of MS. Myelin is the substance that insulates neurons within the central nervous system and is attacked in MS. Infusion of adult bone marrow cells into a vein aids myelin repair (remyelination) in these models of MS. Recently, the investigators performed a small pilot study to examine the effects of harvesting bone marrow from MS patients and infusing this back into each patient's vein. This was well tolerated and no significant adverse events were encountered. Electrophysiological studies appeared to show some improvement but, given the small numbers of participants in the phase 1 trial, no definitive conclusion can be made regarding this.
The current study seeks to address the question of whether genuine improvements in neurophysiological tests are seen in MS patients with progressive disease following infusion of bone marrow.
A prospective, randomised, double-blind, placebo-controlled, stepped wedge design will be employed at a single centre (Bristol, UK). Eighty patients with progressive MS will be recruited; 60 will have secondary progressive disease (SPMS) but a subset (n=20) will have primary progressive disease (PPMS). Participants will be randomised to either early (immediate) or late (1 year) intravenous infusion of autologous, unfractionated bone marrow. The placebo intervention is infusion of autologous blood. The primary outcome measure is global evoked potential derived from multimodal evoked potentials. Secondary outcome measures include adverse event reporting, clinical (EDSS and MSFC) and self-assessment (MSIS-29) rating scales, optical coherence tomography (OCT) as well as brain and spine MRI. Participants will be followed up for a further year following the final intervention. Outcomes will be analyzed on an intention-to-treat basis.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| ISRCTN27232902 | REGISTRY | ISRCTN | View |