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document
Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis ( ACTiMuS ) : study protocol for a randomised controlled trial . BACKGROUND We have recently completed an evaluation of the safety and feasibility of intravenous delivery of autologous bone marrow in patients with progressive multiple sclerosis ( MS ) . The possibility of repair was suggested by improvement in the neurophysiological secondary outcome measure seen in all participants . The current study will examine the efficacy of intravenous delivery of autologous marrow in progressive MS . Laboratory studies performed in parallel with the clinical trial will further investigate the biology of bone marrow-derived stem cell infusion in MS , including mechanisms underlying repair . METHODS/DESIGN 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 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 analysed on an intention-to-treat basis . DISCUSSION Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis ( ACTiMuS ) is the first randomised , placebo-controlled trial of non-myeloablative autologous bone marrow-derived stem cell therapy in MS . It will determine whether bone marrow cell therapy can , as was suggested by the phase I safety study , improve conduction in multiple central nervous system pathways affected in progressive MS . Furthermore , laboratory studies performed in parallel with the clinical trial will inform our understanding of the cellular pharmacodynamics of bone marrow infusion in MS patients and the mechanisms underlying cell therapy . TRIAL REGISTRATION ISRCTN27232902 Registration date 11/09/2012 . NCT01815632 Registration date 19/03/2013 .
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Intervention_Pharmacological
bone marrow-derived Cellular Therapy
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Intervention_Physical
delivery of autologous bone marrow
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Intervention_Pharmacological
intravenous delivery of autologous marrow
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Intervention_Pharmacological
bone marrow-derived stem cell infusion
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
intravenous infusion of autologous , unfractionated bone marrow .
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Intervention_Control
placebo intervention
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Intervention_Control
autologous blood
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Intervention_Pharmacological
bone marrow-derived Cellular Therapy
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Intervention_Pharmacological
non-myeloablative autologous bone marrow-derived stem cell therapy
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Intervention_Pharmacological
bone marrow cell therapy
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Intervention_Pharmacological
cell therapy .
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Outcome_Other
safety
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Outcome_Other
feasibility
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Outcome_Other
efficacy
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Outcome_Other
global evoked potential derived from multimodal evoked potentials .
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Outcome_Adverse-effects
adverse event reporting
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Outcome_Physical
clinical ( EDSS and MSFC ) and self-assessment ( MSIS-29 ) rating scales
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Outcome_Other
optical coherence tomography ( OCT ) as well as brain and spine MRI
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Participant_Condition
progressive Multiple Sclerosis
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Participant_Condition
patients with progressive multiple sclerosis ( MS ) .
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Participant_Sample-size
Eighty patients
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Participant_Sample-size
60
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Participant_Condition
secondary progressive disease ( SPMS )
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Participant_Sample-size
n = 20
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Participant_Condition
primary progressive disease ( PPMS )
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Participant_Condition
progressive MS