Clinical trial NCT00395200: Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS)
Official title: Autologous Adult Human Mesenchymal Stem Cells: a Neuroprotective Therapy for Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Safety
Therapeutics
Mesenchymal Stem Cells
Multipotent Mesenchymal Stromal Cells
Optic Neuritis
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: Cambridge University Hospitals NHS Foundation Trust
name: Medical Research Council
First posted: 2006-11-02
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Adverse events
timeFrame: 0,1,2,3,4,12 and 52 weeks post treatment
Secondary outcomes:
measure: Visual function (acuity and colour)
timeFrame: 12 and 52 weeks post treatment
measure: Visual evoked potential latency
timeFrame: 12 and 52 weeks post treatment
measure: Optic nerve Magnetisation Transfer Ratio
timeFrame: 12 and 52 weeks post treatment
measure: Retinal nerve fibre layer thickness (by optical coherence tomography)
timeFrame: 12 and 52 weeks post treatment
measure: Brain lesion Magnetisation Transfer Ratio
timeFrame: 12 and 52 weeks post treatment
measure: MRI brain T1 hypointensity load
timeFrame: 12 and 52 weeks post treatment
measure: Multiple Sclerosis Functional Composite Score
timeFrame: 12 and 52 weeks post treatment
measure: Expanded Kurtzke Disability Status Score
timeFrame: 12 and 52 weeks post treatment
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: University of Cambridge Dept of Clinical Neurosciences
state: Cambridgeshire
city: London
country: United Kingdom
facility: University College London Institute of Neurology
Study officials:
affiliation: University of Cambridge
name: Siddharthan Chandran, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. 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. Trials. 2011 Mar 2;12:62. doi: 10.1186/1745-6215-12-62.
citation: 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. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol. 2012 Feb;11(2):150-6. doi: 10.1016/S1474-4422(11)70305-2. Epub 2012 Jan 10.