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Trials
Published in: Trials 1/2015

Open Access 01-12-2015 | Study protocol

Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS): study protocol for a randomised controlled trial

Authors: Claire M. Rice, David I. Marks, Yoav Ben-Shlomo, Nikos Evangelou, Paul S. Morgan, Chris Metcalfe, Peter Walsh, Nick M. Kane, Martin G. Guttridge, Gail Miflin, Stuart Blackmore, Pamela Sarkar, Juliana Redondo, Denise Owen, David A. Cottrell, Alastair Wilkins, Neil J. Scolding

Published in: Trials | Issue 1/2015

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Abstract

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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Metadata
Title
Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS): study protocol for a randomised controlled trial
Authors
Claire M. Rice
David I. Marks
Yoav Ben-Shlomo
Nikos Evangelou
Paul S. Morgan
Chris Metcalfe
Peter Walsh
Nick M. Kane
Martin G. Guttridge
Gail Miflin
Stuart Blackmore
Pamela Sarkar
Juliana Redondo
Denise Owen
David A. Cottrell
Alastair Wilkins
Neil J. Scolding
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Trials / Issue 1/2015
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-015-0953-1

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