Assessment of Bone Marrow-derived Cellular Therapy in Progressive Mult

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

Status unknownPhase 2Progressive MSNCT01815632ISRCTN27232902

What it found

Paper found, not read

A paper reports the results; we have not read it yet. See Papers below.

What was tested

Treatment tested

  • Early infusion of autologous marrow
  • Late infusion of autologous marrow

What it measured

Main measures

  • Global evoked potential (GEP): mean change from time of marrow infusion to end of study

    Entry and every 6 months for 2 years

    Myelin repairNerve conduction tests

  • Global evoked potential (GEP)

    Myelin repair

Other measures (7)

  • Safety

    Continuous throughout study period (2 years)

    Safety

  • Expanded disability status scale

    At entry then 6 weeks, 6 months and 1 year after each infusion

    Disability progression

  • Multiple sclerosis impact scale (MSIS-29)

    At entry then 6 weeks, 6 months and 1 year after each infusion

    Quality of life (reported by participants)

  • Multiple sclerosis functional composite (MSFC)

    At entry then 6 weeks, 6 months and 1 year after each infusion

    Disability progression

  • MRI head and cord

    At entry, 1 year and 2 years post-harvest

    MRI lesionsBrain volume lossMyelin repairPhysical functionNerve conduction tests

  • Optical coherence tomography

    Entry, 1 year and 2 years post-harvest

    Retina scans (OCT)

  • 1. EDSS and MSFC and MSIS-29 2. Brain and spinal cord magnetic resonance imaging (MRI) with and without gadolinium-enhancement 3. Optical coherence tomography (OCT)

    Disability progressionMRI lesionsRetina scans (OCT)Quality of life (reported by participants)

Who could take part

Progressive MS · 18 to 65 · EDSS 4.0 to 6

Show the full criteria

Inclusion criteria

* Diagnosis of clinically-definite MS as defined by the McDonald criteria * Aged 18 - 65 years. * EDSS of 4.0 to 6 inclusive * Disease duration >5 years * Disease progression (increase in physical disability, not due to major relapse) in preceding year * Signed, written informed consent * Willing and able to comply with study visits according to protocol for the full study period

Exclusion criteria

* Pregnancy, breastfeeding or lactation * History of autologous/allogenic bone marrow transplantation or peripheral blood stem cell transplant * Bone marrow insufficiency * History of lymphoproliferative disease or previous total lymphoid irradiation * Immune deficiency * Current or recent (\<5 years) malignancy * Chronic or frequent drug-resistant bacterial infections or presence of active infection requiring antimicrobial treatment * Frequent and/or serious viral infection * Systemic or invasive fungal disease within 2 years of entry to study * Significant renal, hepatic, cardiac or respiratory dysfunction * Contraindication to anaesthesia * Bleeding or clotting diathesis * Current or recent (within preceding 12 months) immunomodulatory therapy other than corticosteroid therapy * Treatment with corticosteroids within the preceding three months * Significant relapse within preceding 6 months * Predominantly relapsing-remitting disease over preceding 12 months * Radiation exposure in the past year other than chest / dental x-rays * Previous claustrophobia * The presence of any implanted metal or other contraindication to MRI * Participation in another experimental study or treatment within the preceding 24 months

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

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.

Papers

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History

    1. Started

      Jan 2014

    2. Main results due

      Oct 2019

    3. Finished

      Oct 2019

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