The Effect of Alemtuzumab on the Blood-brain-barrier and the Brain's Metabolism in Multiple Sclerosis Patients
What it found
We found no results in the registry or in papers.
What was tested
Treatment tested
- Alemtuzumab
CAMPATH-1 antigen inhibitor
What it measured
Main measures
Blood-Brain-Barrier Permeability
1 year
MRI lesions
Other measures (9)
Oxygen Consumption
1 year
MRI lesionsCerebral perfusion
1 year
MRI lesionsDiffusion Tensor MRI parameters and MR spectroscopy metabolite concentrations
1 year
MRI lesionsBrain atrophy
2 years
MRI lesionsBrain volume lossClinical Severity of Disease
1 year
Disability progressionRelapse frequency
1 year
RelapsesPlasma markers of Blood-Brain-Barrier breakdown
1 year
Plasma markers of neuronal damage
1 year
Urinary markers of inflammation
1 year
Smouldering inflammationBladder, bowel and sexual function
Who could take part
Relapsing MS · 18 to 60
Inclusion Criteria: * A diagnosis of Relapsing-Remitting Multiple Sclerosis * Eligible for alemtuzumab treatment at Glostrup Hospital or The Danish Kingdom Hospital * Subjects must be deemed physically and mentally able to participate in the study Exclusion Criteria: * Contraindications to MRI scanning (pregnancy, pacemakers, claustrophobia, extreme obesity) * Contraindications to the use of MRI contrast agents (kidney disease, previous allergic reactions) * Conflicting disorders (e.g. disorders with a systemic, inflammatory component)
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
The development and progression of multiple sclerosis seem to be driven by concomitant inflammation and, to a less well-defined degree, disturbances in metabolism of individual cells of the human central nervous system as well as changes in the dynamical supply of blood to the brain. These alterations in normal physiology can be quantified by investigating the change in specific parameters over the time course of multiple sclerosis evolution. Amongst these specific parameters, the ability of the so-called blood-brain-barrier to selectively filter nutrients from the blood stream prior to passage into the nervous tissue, is disrupted in multiple sclerosis, and the severity of this deficiency seem to be related to the underlying disease burden. The present study utilises a novel imaging technology in order to monitor changes in the integrity of the blood-brain-barrier over the course of treatment with a biological disease modifying agent known as alemtuzumab. Alemtuzumab is a potent immunosuppressant drug. It is hypothesised that alemtuzumab reverts the deficiency in blood-brain-barrier integrity and, conversely, the severity of blood-brain-barrier disruption at several time points during alemtuzumab treatment can be utilised as prognostic marker for the requirement of additional administration of alemtuzumab beyond the regular treatment regimen. In addition, several other factors are investigated by advanced imaging techniques in combination with blood and urine samples in order to elucidate the possible underlying mechanism of alemtuzumab efficacy. It is hypothesized that alemtuzumab normalises metabolic alterations and changes in the blood supply through resolution of inflammation in the brains of multiple sclerosis patients.
Papers
Background
Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002 Jun;15(3):239-45. doi: 10.1097/00019052-200206000-00003.Background
Cramer SP, Larsson HB. Accurate determination of blood-brain barrier permeability using dynamic contrast-enhanced T1-weighted MRI: a simulation and in vivo study on healthy subjects and multiple sclerosis patients. J Cereb Blood Flow Metab. 2014 Oct;34(10):1655-65. doi: 10.1038/jcbfm.2014.126. Epub 2014 Jul 30.Background
Broholm H, Andersen B, Wanscher B, Frederiksen JL, Rubin I, Pakkenberg B, Larsson HB, Lauritzen M. Nitric oxide synthase expression and enzymatic activity in multiple sclerosis. Acta Neurol Scand. 2004 Apr;109(4):261-9. doi: 10.1111/j.1600-0404.2004.00207.x.Background
Cramer SP, Modvig S, Simonsen HJ, Frederiksen JL, Larsson HB. Permeability of the blood-brain barrier predicts conversion from optic neuritis to multiple sclerosis. Brain. 2015 Sep;138(Pt 9):2571-83. doi: 10.1093/brain/awv203. Epub 2015 Jul 17.Background
D'haeseleer M, Cambron M, Vanopdenbosch L, De Keyser J. Vascular aspects of multiple sclerosis. Lancet Neurol. 2011 Jul;10(7):657-66. doi: 10.1016/S1474-4422(11)70105-3.Background
Gauthier SA, Berger AM, Liptak Z, Duan Y, Egorova S, Buckle GJ, Glanz BI, Khoury SJ, Bakshi R, Weiner HL, Guttmann CR. Rate of brain atrophy in benign vs early multiple sclerosis. Arch Neurol. 2009 Feb;66(2):234-7. doi: 10.1001/archneurol.2008.567.Background
Ge Y, Zhang Z, Lu H, Tang L, Jaggi H, Herbert J, Babb JS, Rusinek H, Grossman RI. Characterizing brain oxygen metabolism in patients with multiple sclerosis with T2-relaxation-under-spin-tagging MRI. J Cereb Blood Flow Metab. 2012 Mar;32(3):403-12. doi: 10.1038/jcbfm.2011.191. Epub 2012 Jan 18.Background
De Keyser J, Steen C, Mostert JP, Koch MW. Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance. J Cereb Blood Flow Metab. 2008 Oct;28(10):1645-51. doi: 10.1038/jcbfm.2008.72. Epub 2008 Jul 2.Background
Larsson HB, Stubgaard M, Frederiksen JL, Jensen M, Henriksen O, Paulson OB. Quantitation of blood-brain barrier defect by magnetic resonance imaging and gadolinium-DTPA in patients with multiple sclerosis and brain tumors. Magn Reson Med. 1990 Oct;16(1):117-31. doi: 10.1002/mrm.1910160111.Background
Larsson HB, Courivaud F, Rostrup E, Hansen AE. Measurement of brain perfusion, blood volume, and blood-brain barrier permeability, using dynamic contrast-enhanced T(1)-weighted MRI at 3 tesla. Magn Reson Med. 2009 Nov;62(5):1270-81. doi: 10.1002/mrm.22136.
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History
Started
Jan 2017
Main results due
Mar 2020
Finished
Mar 2020
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