Background
Methods
Trial design
Trial Centres
Trial objectives
Participant Selection
Clinically definite multiple sclerosis |
---|
Expanded Kurtzke Disability Status Score (EDSS) 2.0 - 6.5 inclusive |
Clinical evidence of optic nerve involvement on history or examination* |
Abnormal visual evoked potential from one or both eyes suggestive of demyelination |
Retinal nerve fibre layer (RNFL) thickness of at least 45 microns in one eye |
T2 lesion on MRI of optic nerve |
Age 18 - 65 inclusive |
Capacity to give consent |
No serious underlying bleeding disorder |
Not on Beta-interferon or Glatiramer acetate within six months of trial entry and not previously on other disease modifying therapies at any point |
Recruitment
MSC isolation, expansion, characterisation & pre-administration safety checks
Intervention dose, route, and administration procedures
Outcome selection & assessment schedule
Clinical outcome measures
Paraclinical outcome measures
MR imaging methodology
(i) Optic nerve imaging
(ii) Brain
Data & Safety Monitoring
Blinding and data analysis
Ethical approval and trial-registration
Results
Recruitment & retention of participants
Participant characteristics
Participant | Age | Sex | MS Phenotype | Duration of MS (years) | EDSS at entry | Clinical episode of optic neuritis | Optic nerve affected | Time elapsed since first clinical episode of optic neuritis (years) |
---|---|---|---|---|---|---|---|---|
1
| 44 | Male | SPMS | 19 | 6 | Yes | Right | 19 |
2
| 51 | Male | SPMS | 26 | 6 | Yes | Both | 26 (left); 9 (right) |
3
| 40 | Female | SPMS | 13 | 6.5 | No | Left* | 6 |
4
| 48 | Male | SPMS | 27 | 6 | Yes | Left | 27 |
5
| 48 | Male | SPMS | 12 | 6.5 | Yes | Right | 11 |
6
| 52 | Male | SPMS | 18 | 6 | Yes | Right | 18 & 13 |
7
| 53 | Female | SPMS | 5 | 6 | Yes | Left | 6 |
8
| 51 | Male | SPMS | 7 | 5.5 | Yes | Both | 2 (left); 7 (right) |
9
| 46 | Female | SPMS | 11 | 6 | Yes | Both | 5 |
10
| 51 | Male | SPMS | 6 | 6.5 | Yes | Both | 6 |
MSC culture results
Baseline assessment results
(i) Patient-based measures
Mean | SD | Range | |
---|---|---|---|
BDI-II score
| 8.2 | 7.6 | 1 - 25 |
MSIS-29 Physical score
| 66.3 | 9.5 | 51 - 80 |
MSIS Psychological score
| 20.7 | 5.2 | 11 - 27 |
EDSS
| 6.1 | 0.3 | 5.5 - 6.5 |
ACE-R score
| 92.4 | 5.9 | 85 - 100 |
MSFC (total) z-score
| -1.5 | 1.4 | -5.4 - -0.4 |
MSFC (arm) z-score
| -1.5 | 0.6 | -2.7 - -0.7 |
MSFC (leg) z-score
| -2.0 | 4.1 | -13.7 - -0.3 |
MSFC (cognitive) z-score
| -0.9 | 1.1 | -2.1 - 1.2 |
Normalised brain volume (ml)
| 1486 | 75 | 1361 - 1586 |
T
2
lesion volume (cm
3
)
| 40.5 | 30.1 | 3.4 - 99.5 |
T
1
lesion volume (cm
3
)
| 10.2 | 9.5 | 0.6 - 31.3 |
(ii) Optic nerve-based measures
Clinically Affected (mean, SD) | Clinically Unaffected (mean, SD) | p | |
---|---|---|---|
Number of optic nerves (n)
| 14 | 6 | |
LogMAR
| 0.15 (0.20) | 0.15 (0.17) | 0.9640 |
Sloan 25%
| 0.31 (0.26) | 0.30 (0.20) | 0.9746 |
Sloan 5%
| 0.66 (0.35) | 0.53 (0.18) | 0.4282 |
Sloan 1.25%
| 1.0 (0.46) | 0.75 (0.15) | 0.1544 |
FM-100 Square-Root Total Error Score
| 16.0 (4.4) | 13.5 (2.8) | 0.2188 |
Visual field Mean Deviance
| -4.28 (2.04) | -3.04 (2.06) | 0.2267 |
RNFL average thickness (microns)
| 72.4 (12.9) | 85.5 (10.2) | 0.0399 |
Macular volume (mm
3
)
| 6.1 (0.5) | 6.6 (0.3) | 0.0624 |
Full field VER latency (milliseconds)
| 136.3 (15.2) | 114.8 (7.1) | 0.0045 |
Full-field VER amplitude (microvolts)
| 4.8 (1.9) | 4.5 (2.3) | 0.7669 |
Optic nerve area (mm
2
)
| 8.1 (1.3) | 8.9 (1.1) | 0.1961 |
Optic nerve MTR (pu)
| 28.4 (2.9) | 31.3 (2.3) | 0.0515 |
Optic nerve DTI Mean Diffusivity (×10
-3
mm
2
/s)
| 1.17 (0.29) | 1.25 (0.26) | 0.5415 |
Optic nerve DTI Fractional Anisotropy (×10
3
)
| 298.2 (91.2) | 353.3 (88.6) | 0.2282 |
Optic nerve DTI Radial Diffusivity (×10
-3
mm
2
/s)
| 0.99 (0.26) | 1.03 (0.24) | 0.7004 |
Optic nerve DTI Axial Diffusivity (×10
-3
mm
2
/s)
| 1.53 (0.42) | 1.70 (0.35) | 0.4012 |
(iii) Comparative performance between patients and controls
PATIENTS | CONTROLS | |||
---|---|---|---|---|
Clinically Affected (mean, SD) | Clinically Unaffected (mean, SD) | (mean, SD) | p* | |
Number of optic nerves (n)
| 14 | 6 | 16 | - |
RNFL average thickness (microns)
| 72.4 (12.9) | 85.5 (10.2) | 101.6 (12.1) | 0.0093 |
Macular volume (mm
3
)
| 6.1 (0.5) | 6.6 (0.3) | 6.9 (0.4) | 0.1211 |
Optic nerve area (mm
2
)
| 8.1 (1.3) | 8.9 (1.1) | 10.3 (0.8) | 0.0123 |
Optic nerve MTR (pu)
| 28.4 (2.9) | 31.3 (2.3) | 32.9 (3.4) | 0.2700 |
Optic nerve DTI Mean Diffusivity (×10
-3
mm
2
/s)
| 1.17 (0.29) | 1.25 (0.26) | 0.97 (0.13) | 0.0145 |
Optic nerve DTI Fractional Anisotropy (×10
3
)
| 298.2 (91.2) | 353.3 (88.6) | 530.6 (99.7) | 0.0004 |
Optic nerve DTI Radial Diffusivity (×10
-3
mm
2
/s)
| 0.99 (0.26) | 1.03 (0.24) | 0.67 (0.13) | 0.0007 |
Optic nerve DTI Axial Diffusivity (×10
-3
mm
2
/s)
| 1.53 (0.42) | 1.70 (0.35) | 1.58 (0.23) | 0.4809 |