Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS)

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis, Safety, Therapeutics, Mesenchymal Stem Cells, Multipotent Mesenchymal Stromal Cells, Optic Neuritis

Brief summary

Hypothesis: Intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells is a safe novel therapeutic approach for patients with multiple sclerosis. Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) is a phase I/IIA trial designed to establish the safety of intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells to patients with multiple sclerosis.

Detailed description

Disease under investigation: Multiple Sclerosis Phase: I/IIA Number of patients: 10 Design: 18 month cross over, single treatment at 6 months Intervention: Administration of bone marrow-derived autologous mesenchymal stem cells Route of administration: Intravenous Dose: Up to 2,000,000 Mesenchymal Stem Cells per kilogram Source of patients: Referrals accepted from Neurologists in East Anglia and North London, UK Referral Criteria: (all 3 required) 1. Clinically definite multiple sclerosis 2. Expanded Kurtzke Disability Status Score 2.0 - 6.5 (inclusive) 3. Evidence of optic nerve damage by * history of optic neuritis, or * relative afferent pupillary defect, or * optic atrophy on fundoscopy, or * abnormal visual evoked potential from either or both eyes suggestive of demyelination Primary Objective: Establish the safety of intravenously administered bone marrow-derived autologous mesenchymal stem cells at a dose of up to 2,000,000 cells/kg over 12 months by monitoring adverse reactions. Secondary Objectives: Explore the efficacy of intravenously administered bone marrow-derived autologous mesenchymal stem cells at a dose of up to 2,000,000 cells/kg over 12 months on visual function by clinical, neurophysiological, and imaging assessments. Outcome Measures: 1. Primary * Adverse events 2. Secondary * Visual function (acuity and colour) * Visual evoked potential latency * Optic nerve Magnetisation Transfer Ratio * Retinal nerve fibre layer thickness (by optical coherence tomography) * Brain lesion Magnetisation Transfer Ratio * MRI brain T1 hypointensity load * T cell response suppression 3. Tertiary * Multiple Sclerosis Functional Composite Score * Expanded Kurtzke Disability Status Score

Peter Connick, Siddharthan Chandran

Journal of Neurology Neurosurgery & Psychiatry2013-10-0938 citations

10.1136/jnnp-2013-306573.25

Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study.

Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, Du MQ, Luan SL, Altmann DR, Thompson AJ, Compston A, Scott MA, Miller DH, Chandran S.

2012-01-10439 citations

10.1016/s1474-4422(11)70305-2

The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments.

Connick P, Kolappan M, Patani R, Scott MA, Crawley C, He XL, Richardson K, Barber K, Webber DJ, Wheeler-Kingshott CA, Tozer DJ, Samson RS, Thomas DL, Du MQ, Luan SL, Michell AW, Altmann DR, Thompson AJ, Miller DH, Compston A, Chandran S.

2011-03-0283 citations

10.1186/1745-6215-12-62

Papers published before 2007-09-01 may not appear yet. Historical indexing is in progress.

Interventions

PROCEDUREMSC Treatment

Intravenous administration of up to 2x10\^6 autologous MSCs per kg

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

No

Inclusion criteria

* Clinically definite multiple sclerosis * Expanded Kurtzke Disability Status Score 2.0 - 6.5 (inclusive) * Evidence of optic nerve damage by: * history of optic neuritis, or * relative afferent pupillary defect, or * optic atrophy on fundoscopy, or * abnormal visual evoked potential from either or both eyes suggestive of demyelination * Prolonged visual evoked potential P100 latency with preserved waveform * T2 lesion on MRI optic nerve * Retinal nerve fibre layer thickness on optical coherence tomography \> 40 microns

Exclusion criteria

* Age \< 18 years * Age \> 65 years * Patient lacks capacity to give informed consent * Presence of a severe bleeding disorder * Planning a pregnancy during the trial period * Current MS disease modifying therapy

Design outcomes

Primary

Measure	Time frame
Adverse events	0,1,2,3,4,12 and 52 weeks post treatment

Secondary

Measure	Time frame
Optic nerve Magnetisation Transfer Ratio	12 and 52 weeks post treatment
Visual function (acuity and colour)	12 and 52 weeks post treatment
Retinal nerve fibre layer thickness (by optical coherence tomography)	12 and 52 weeks post treatment
Visual evoked potential latency	12 and 52 weeks post treatment
MRI brain T1 hypointensity load	12 and 52 weeks post treatment
Multiple Sclerosis Functional Composite Score	12 and 52 weeks post treatment
Expanded Kurtzke Disability Status Score	12 and 52 weeks post treatment
Brain lesion Magnetisation Transfer Ratio	12 and 52 weeks post treatment

Countries

United Kingdom

Outcome results

None listed