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

NCT01815632 | Unknown Phase 2 DMC

• 2 other identifiers: ACTiMuSISRCTN27232902
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Progressive Multiple Sclerosis

Keywords

multiple sclerosis; progressive MS; stem cell; cell therapy; neurodegeneration; CNS repair

Outcome Measures

Primary Outcomes (1)

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

  Multimodal evoked potentials will be examined at 0, 6, 12, 18 and 24 months. Evoked potential abnormalities will be quantified according to a 4-point graded ordinal score modified from Leocani et al (JNNP 2006, 77:1030-1035) (0=normal; 1=increased latency; 2=increased latency and abnormal amplitude; 3=absent). The recording of the evoked potentials shall be in accordance with the Guidelines of the International Federation of Clinical Neurophysiology and analysis will be performed using standard methods. Electrophysiological responses shall be considered abnormal if they exceed 2.5 standard deviations of the normal values or cannot be detected.

  Entry and every 6 months for 2 years

Secondary Outcomes (6)

• Safety

  Continuous throughout study period (2 years)

• Expanded disability status scale

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

• Multiple sclerosis impact scale (MSIS-29)

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

• Multiple sclerosis functional composite (MSFC)

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

• MRI head and cord

  At entry, 1 year and 2 years post-harvest

Study Arms (2)

Early infusion of autologous marrow

EXPERIMENTAL

Intravenous infusion of autologous bone marrow (without myeloablation) on the day of bone marrow harvest. Infusion of autologous blood at one year post-harvest

Other: Early infusion of autologous marrow

Late infusion of autologous marrow

EXPERIMENTAL

Intravenous infusion of autologous blood on the day of bone marrow harvest. Infusion of autologous bone marrow (without myeloablation) at one year post-harvest

Other: Late infusion of autologous marrow

Interventions

Early infusion of autologous marrow OTHER

Intravenous infusion of autologous bone marrow without prior myeloablation on the day of bone marrow harvest and infusion of autologous blood at one year post-bone marrow harvest

Early infusion of autologous marrow

Late infusion of autologous marrow OTHER

Infusion of blood on day of bone marrow harvest with intravenous infusion of autologous bone marrow without prior myeloablation one year post-bone marrow harvest.

Late infusion of autologous marrow

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• North Bristol NHS Trust: lead
• Bristol Royal Hospital for Children: collaborator
• University of Bristol: collaborator
• University of Nottingham: collaborator
• NHS Blood and Transplant: collaborator
• Kenneth and Claudia Silverman Family Foundation: collaborator
• Multiple Sclerosis Trust: collaborator
• Medical Research Council: collaborator
• Rosetrees Trust: collaborator
• Catholic Bishops of England and Wales: collaborator
• Friends of Frenchay: collaborator

Study Sites (1)

Southmead Hospital

Bristol, BS10 5NB, United Kingdom

RECRUITING

Related Publications (1)

• Rice CM, Marks DI, Ben-Shlomo Y, Evangelou N, Morgan PS, Metcalfe C, Walsh P, Kane NM, Guttridge MG, Miflin G, Blackmore S, Sarkar P, Redondo J, Owen D, Cottrell DA, Wilkins A, Scolding NJ. Assessment of bone marrow-derived Cellular Therapy in progressive Multiple Sclerosis (ACTiMuS): study protocol for a randomised controlled trial. Trials. 2015 Oct 14;16:463. doi: 10.1186/s13063-015-0953-1.

  PMID: 26467901 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis; Nerve Degeneration

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Neil J Scolding, FRCP PhD

  University of Bristol & North Bristol NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claire M Rice, MA MRCP PhD

CONTACT

00 44 117 4146695; claire.rice@nbt.nhs.uk

Neil J Scolding, PhD FRCP

CONTACT

00 44 117 4146694; heather.williams@nbt.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2013
• First Posted: March 21, 2013
• Study Start: January 1, 2014
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: June 27, 2018

Record last verified: 2018-06

Locations

GB (1)