Trial record 2 of 64 for:    Autologous Bone and harvest

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by North Bristol NHS Trust
Sponsor:
Collaborator:
Sir Halley Stewart Trust
Information provided by (Responsible Party):
North Bristol NHS Trust
ClinicalTrials.gov Identifier:
NCT01932593
First received: August 13, 2013
Last updated: April 16, 2015
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Procedure: Infusion of autologous bone marrow
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Repeat Infusion of Autologous Bone Marrow Cells in Multiple Sclerosis (SIAMMS-II)

Resource links provided by NLM:


Further study details as provided by North Bristol NHS Trust:

Primary Outcome Measures:
  • Adverse events [ Time Frame: 1 year post-infusion of autologous bone marrow ] [ Designated as safety issue: Yes ]
    Number of adverse events


Secondary Outcome Measures:
  • Global evoked potential [ Time Frame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow ] [ Designated as safety issue: Yes ]
    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.

  • MRI brain [ Time Frame: Baseline and 6 months post-infusion of autologous bone marrow ] [ Designated as safety issue: Yes ]
    MRI brain scan

  • Expanded disability status scale (EDSS) [ Time Frame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow ] [ Designated as safety issue: Yes ]
    Expanded disability status scale - clinical scale of disability used in MS trials

  • Multiple sclerosis functional composite (MSFC) [ Time Frame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow ] [ Designated as safety issue: Yes ]
    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).

  • Multiple sclerosis impact scale (MSIS-29) [ Time Frame: Baseline then 6 months and 12 months post-infusion of autologous bone marrow ] [ Designated as safety issue: Yes ]
    Self-reporting questionnaire re impact of MS


Other Outcome Measures:
  • Tolerability [ Time Frame: Ongoing post-infusion of autologous bone marrow with a formal request for feedback at 12 months ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 6
Study Start Date: January 2014
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Infusion of autologous bone marrow
Bone marrow harvest under general anaesthetic and intravenous infusion of filtered but otherwise unselected autologous bone marrow
Procedure: Infusion of autologous bone marrow
Bone marrow harvest under general anaesthetic and intravenous infusion of filtered but otherwise unselected autologous bone marrow

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

Ages Eligible for Study:   25 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01932593

Contacts
Contact: Neil J Scolding, PhD FRCP 00 44 (0)117 3406632 heather.williams@nbt.nhs.uk
Contact: Claire M Rice, MA MRCP PhD 00 44 (0)117 3406636 claire.rice@nbt.nhs.uk

Locations
United Kingdom
North Bristol NHS Trust Recruiting
Bristol, Avon, United Kingdom, BS16 1LE
Principal Investigator: Neil J Scolding, PhD FRCP         
Sub-Investigator: Claire M Rice, MA MRCP PhD         
Sponsors and Collaborators
North Bristol NHS Trust
Sir Halley Stewart Trust
Investigators
Principal Investigator: Neil J Scolding, PhD FRCP North Bristol NHS Trust and University of Bristol
  More Information

No publications provided

Responsible Party: North Bristol NHS Trust
ClinicalTrials.gov Identifier: NCT01932593     History of Changes
Other Study ID Numbers: SIAMMS-II
Study First Received: August 13, 2013
Last Updated: April 16, 2015
Health Authority: United Kingdom: NHS Health Research Authority

Keywords provided by North Bristol NHS Trust:
multiple sclerosis
bone marrow
stem cell therapy

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on September 01, 2015