Assessment of Bone Marrow-derived Cellular Therapy in Progressive Multiple Sclerosis (ACTiMuS)

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.

Conditions

• Progressive Multiple Sclerosis

Interventions

OTHER

Early infusion of autologous marrow

Intravenous infusion of autologous bone marrow without prior myeloablation on the day of bone marrow harvest and infusion of autologous blood at one year post-bone marrow harvest

OTHER

Late infusion of autologous marrow

Infusion of blood on day of bone marrow harvest with intravenous infusion of autologous bone marrow without prior myeloablation one year post-bone marrow harvest.

Sponsors & Collaborators

• Bristol Royal Hospital for Children

  collaborator OTHER

• University of Bristol

  collaborator OTHER

• University of Nottingham

  collaborator OTHER

• NHS Blood and Transplant

  collaborator OTHER_GOV

• Kenneth and Claudia Silverman Family Foundation

  collaborator OTHER

• Multiple Sclerosis Trust

  collaborator UNKNOWN

• Medical Research Council

  collaborator OTHER_GOV

• Rosetrees Trust

  collaborator OTHER

• Catholic Bishops of England and Wales

  collaborator UNKNOWN

• Friends of Frenchay

  collaborator UNKNOWN

• North Bristol NHS Trust

  lead OTHER

Principal Investigators

• Neil J Scolding, FRCP PhD · University of Bristol & North Bristol NHS Trust

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-01-31

Primary Completion

2019-10-31

Completion

2019-10-31

Countries

• United Kingdom

Study Locations