Repeat Infusion of Autologous Bone Marrow Cells in Multiple Sclerosis

Multiple Sclerosis Clinical Trial

— SIAMMS-II  

Official title:

Repeat Infusion of Autologous Bone Marrow Cells in Multiple Sclerosis (SIAMMS-II)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01932593
• Other study ID #: SIAMMS-II
• Status: Completed
• Phase: N/A
• Start date: January 31, 2014
• Est. completion date: August 20, 2018

Study information

• Verified date: August 2018
• Source: North Bristol NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: August 20, 2018
• Est. primary completion date: September 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Procedure:
• Infusion of autologous bone marrow
Bone marrow harvest under general anaesthetic and intravenous infusion of filtered but otherwise unselected autologous bone marrow

Locations

Country	Name	City	State
United Kingdom	North Bristol NHS Trust	Bristol	Avon

Sponsors (2)

Lead Sponsor	Collaborator
North Bristol NHS Trust	Sir Halley Stewart Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tolerability	Participants will be encouraged to report their experience of the procedure at any time and to submit a written statement at 12 months post-infusion of autologous bone marrow	Ongoing post-infusion of autologous bone marrow with a formal request for feedback at 12 months
Primary	Adverse events	Number of adverse events	1 year post-infusion of autologous bone marrow
Secondary	Global evoked potential	The 'global evoked potential (GEP)' has been developed as a tool that, by combining multimodal evoked potential recordings to a single score, may be used to monitor the evolution of MS in individual patients, and as a surrogate end point in clinical trials.	Baseline then 6 months and 12 months post-infusion of autologous bone marrow
Secondary	MRI brain	MRI brain scan	Baseline and 6 months post-infusion of autologous bone marrow
Secondary	Expanded disability status scale (EDSS)	Expanded disability status scale - clinical scale of disability used in MS trials	Baseline then 6 months and 12 months post-infusion of autologous bone marrow
Secondary	Multiple sclerosis functional composite (MSFC)	The MSFC is a three-part quantitative assessment of disability and includes a timed walk, the nine-hole peg test and the Paced Auditory Serial Addition Test (PASAT).	Baseline then 6 months and 12 months post-infusion of autologous bone marrow
Secondary	Multiple sclerosis impact scale (MSIS-29)	Self-reporting questionnaire re impact of MS	Baseline then 6 months and 12 months post-infusion of autologous bone marrow