Clinical trial NCT01932593: Repeat Infusion of Autologous Bone Marrow Cells in Multiple Sclerosis
Official title: Repeat Infusion of Autologous Bone Marrow Cells in Multiple Sclerosis (SIAMMS-II)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Keywords: multiple sclerosis
bone marrow
stem cell therapy
Lead sponsor: North Bristol NHS Trust
Sponsor class: OTHER
Collaborators: name: Sir Halley Stewart Trust
First posted: 2013-08-30
Enrollment: 4
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: autologous bone marrow cells
Primary purpose: TREATMENT

Brief 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).

Eligibility criteria: Inclusion Criteria:

Participation in the phase I safety and feasibility 'Study of Intravenous Autologous Marrow in Multiple Sclerosis' (SIAMMS) (REC reference number number 05/Q1704/137 Clin Pharmacol Ther. 2010 Jun;87(6):679-85)

Exclusion Criteria:

* pregnancy, breastfeeding or lactation
* bone marrow insufficiency
* history of lymphoproliferative disease or previous total lymphoid irradiation immune deficiency
* history of 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 3 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 previous 24 months

Primary outcomes:
measure: Adverse events
timeFrame: 1 year post-infusion of autologous bone marrow
Secondary outcomes:
measure: Global evoked potential
timeFrame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
measure: MRI brain
timeFrame: Baseline and 6 months post-infusion of autologous bone marrow
measure: Expanded disability status scale (EDSS)
timeFrame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
measure: Multiple sclerosis functional composite (MSFC)
timeFrame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
measure: Multiple sclerosis impact scale (MSIS-29)
timeFrame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow
Other outcomes:
measure: Tolerability
timeFrame: Ongoing post-infusion of autologous bone marrow with a formal request for feedback at 12 months
Locations:
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
state: Avon
Study officials:
affiliation: North Bristol NHS Trust and University of Bristol
name: Neil J Scolding, PhD FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rice CM, Marks DI, Walsh P, Kane NM, Guttridge MG, Redondo J, Sarkar P, Owen D, Wilkins A, Scolding NJ. Repeat infusion of autologous bone marrow cells in multiple sclerosis: protocol for a phase I extension study (SIAMMS-II). BMJ Open. 2015 Sep 11;5(9):e009090. doi: 10.1136/bmjopen-2015-009090.