Repeat Infusion of Autologous Bone Marrow Cells in Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional

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.

      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).
    

Intervention name(s): Infusion of autologous bone marrow
Intervention type(s): Procedure
Intervention description(s): Bone marrow harvest under general anaesthetic and intravenous infusion of filtered but otherwise unselected autologous bone marrow
Allocation: Randomized
Intervention model: Single Group Assignment
Intervention model description: autologous bone marrow cells
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: multiple sclerosis; bone marrow; stem cell therapy