Multiple SclerosisNCT03193086
The Effect of Alemtuzumab on the Blood-brain-barrier and the Brain's Metabolism in Multiple Sclerosis Patients
An observational study of Multiple Sclerosis, run by Glostrup University Hospital, Copenhagen at 1 site in Denmark.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Alemtuzumab
- Type of treatment
- Injection or infusion
- How many people
- 35 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Jan 2017to 31 Mar 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Study population: Patients are recruited from the two dedicated MS clinics in the secondary health care sector of the danish capital region.
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Functional Imaging Unit, Department of Clinical Physiology, Nuclear medicine and PET, Glostrup Hospital
Glostrup Municipality, Copenhagen Capital Region, 2600
Peter F Svane, MD, 93906653 ext. 45, peter.frederiksen.svane@hotmail.com
Stig P Cramer, MD, PhD, 38634624 ext. 45, stig.praestekjaer.cramer@regionh.dk
About this study
Official title: The Effect of Alemtuzumab on the Blood-brain-barrier and Cerebral Metabolism in Multiple Sclerosis Patients; a New MRI Method for Treatment Response Evaluation in Multiple Sclerosis
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.
Read the detailed description
Traditional paraclinical measures of disease severity in multiple sclerosis (MS), such as T2 lesion load as measured by magnetic resonance imaging (MRI), are poorly correlated with long-term disability accumulation. Other surrogate markers of the current and future disease burden are therefore needed. The permeability of the blood-brain-barrier (BBB) seems to better reflect the substantial, subclinical disease activity underlying MS progression. Its useful role as a prognostic marker in MS has been clearly established by the recent observation that BBB permeability increase in optic neuritis patients is associated with conversion to definite MS. BBB permeability can be quantified, in a convenient manner to the patient, using Dynamic-Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) by modelling the change in intrinsic MRI parameters of the human brain in response to the administration of a bolus contrast agent. Alemtuzumab is a disease modifying drug that depletes T- and B-cells. It is administered in two series separated by 12 months, as explained in the section "Groups and Interventions." The number of relapses are significantly reduced as compared to other efficacious treatments in MS, as demonstrated recently (study referred to by its ClinicalTrials.gov identifier NCT00050778). The efficacy of alemtuzumab in resolving the inflammatory burden underlying relapses is, thus, well-established. Its influence on subclinical inflammation, however, remains unknown. It is the aim of the present study to investigate whether or not the latter influence is of importance, and, consequently, can be used to evaluate the need for an intensified treatment, in the form of an additional series of alemtuzumab administration.
BBB permeability changes, as surrogate markers of subclinical inflammation, are measured every 6 months just prior to and during the course of alemtuzumab treatment. In order to elucidate other potential mechanisms involved in disability accumulation, biomarkers and MRI-derived parameters are evaluated concomitantly. Specifically, the role of metabolic changes are investigated using MRI methods that measures blood perfusion and oxygen consumption. Secondarily, the BBB permeability and metabolic changes are correlated to novel biomarkers of inflammation and neurodegeneration in serum and urine, as well as conventional measures of MS severity: annual relapse rate, Expanded Disability Severity Score, MRI-derived estimates of disease activity and brain atrophy.
35 patients are included in the study in order to achieve enough statistical power and accommodate drop-outs. Patients are MRI scanned at baseline, 6 months after alemtuzumab treatment, and, finally, prior to administration of the second series of alemtuzumab 12 months after the baseline MRI scanning. At each time point, the patient's disease status is evaluated by an experienced neurologist, and urine and serum samples are obtained. Repeated Measures Analysis Of Variance (ANOVA) will be used to evaluate changes of permeability of the BBB and metabolic parameters at different time points, and baseline characteristics, such as prednisolone treatment will be implemented as between-subjects covariates. Logistic regression will be applied to estimate the ability of BBB permeability changes to predict the need for additional series of alemtuzumab administration.
- Conditions
- Multiple Sclerosis
- Being tested
- Alemtuzumab
- Keywords
- Multiple Sclerosis, Blood-Brain-Barrier, Treatment response, Metabolism, Alemtuzumab, Perfusion, Oxygen consumption
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlemtuzumabDrug
Also called Lemtrada
Alemtuzumab is administered to eligible patients in accordance with established treatment regimes. Initially 60 mg of alemtuzumab is injected intravenously over the course of 5 days. The first treatment series is followed by the injection of 36 mg of alemtuzumab over the course of 3 days 12 months later. During both drug interventions, the transient exacerbation in disease severity is alleviated by concomitant steroid therapy.
| Study group | Role | What they receive |
|---|---|---|
| Alemtuzumab treated MS patients | Those with Multiple Sclerosis that have commenced therapy with alemtuzumab (60 mg infusion over the course of 5 days) and completed treatment with alemtuzumab (additional 36 mg infusion during the course of 3 days, 12 months later). Receives: Drug: Alemtuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood-Brain-Barrier Permeability
Blood-Brain-Barrier Permeability as measured by Dynamic-Contrast-Enhanced MRI (DCE-MRI)
Measured: 1 year
Secondary outcomes (9)
Oxygen Consumption
The Cerebral Metabolic Rate of Oxygen Consumption as measured by a novel MRI technique
Measured: 1 year
Cerebral perfusion
Quantification of cerebral perfusion using DCE-MRI and Arterial-Spin-Labelling MRI
Measured: 1 year
Diffusion Tensor MRI parameters and MR spectroscopy metabolite concentrations
Measurement of changes in microstructural organization as measured by Diffusion Tensor MRI
Measured: 1 year
Brain atrophy
Voxel-Based-Morphometry of grey and white matter utilizing high-resolution MRI
Measured: 2 years
Clinical Severity of Disease
Estimation of disease severity by the Expanded Disability Severity Scale (EDSS)
Measured: 1 year
Relapse frequency
Number of relapses during follow-up and past history
Measured: 1 year
Plasma markers of Blood-Brain-Barrier breakdown
Detection of markers associated with Blood-Brain-Barrier breakdown nervous system
Measured: 1 year
Plasma markers of neuronal damage
Detection of markers associated with neuronal damage
Measured: 1 year
Urinary markers of inflammation
Detection of markers associated with inflammatory activity specific to macrophages/microglia in the human central nervous system
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2017
- Study start1 Jan 2017
- Primary completion31 Mar 2020 (estimated)
- Study completion31 Mar 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Glostrup University Hospital, Copenhagen
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Principal investigator, Peter FredSvan, Glostrup University Hospital, Copenhagen
- Investigators
- Henrik BW Larsson, MD, Prof., Study director, Functional Imaging Unit, Department of Clinical Physiology, Nuclear medicine and PET, Glostrup Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03193086
- Sponsor's protocol ID
- GZ-2016-11629
- Status last verified
- Jun 2017
- First submitted
- 14 Jun 2017
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 12045719Cramer 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.
PubMed 25074746Broholm 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.
PubMed 15016008Cramer 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.
PubMed 26187333D'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.
PubMed 21683931Gauthier 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.
PubMed 19204160Ge 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.
PubMed 22252237De 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.
PubMed 18594554Larsson 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.
PubMed 2255233Larsson 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.
PubMed 19780145Law M, Saindane AM, Ge Y, Babb JS, Johnson G, Mannon LJ, Herbert J, Grossman RI. Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology. 2004 Jun;231(3):645-52. doi: 10.1148/radiol.2313030996.
PubMed 15163806Naismith RT, Cross AH. Enhancing our understanding of white matter changes in early multiple sclerosis. Brain. 2015 Sep;138(Pt 9):2465-6. doi: 10.1093/brain/awv196. No abstract available.
PubMed 26304148Scalfari A, Neuhaus A, Degenhardt A, Rice GP, Muraro PA, Daumer M, Ebers GC. The natural history of multiple sclerosis: a geographically based study 10: relapses and long-term disability. Brain. 2010 Jul;133(Pt 7):1914-29. doi: 10.1093/brain/awq118. Epub 2010 Jun 9.
PubMed 20534650Steen C, D'haeseleer M, Hoogduin JM, Fierens Y, Cambron M, Mostert JP, Heersema DJ, Koch MW, De Keyser J. Cerebral white matter blood flow and energy metabolism in multiple sclerosis. Mult Scler. 2013 Sep;19(10):1282-9. doi: 10.1177/1352458513477228. Epub 2013 Feb 21.
PubMed 23428956Sun X, Tanaka M, Kondo S, Okamoto K, Hirai S. Clinical significance of reduced cerebral metabolism in multiple sclerosis: a combined PET and MRI study. Ann Nucl Med. 1998 Apr;12(2):89-94. doi: 10.1007/BF03164835.
PubMed 9637279
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Alemtuzumab on the Blood-brain-barrier and Cerebral Metabolism in Multiple Sclerosis Patients; a New MRI Method for Treatment Response Evaluation in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT03193086
- Acronym / sponsor ID
- GZ-2016-11629
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Blood-Brain-Barrier, Treatment response, Metabolism, Alemtuzumab, Perfusion, Oxygen consumption
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Glostrup University Hospital, CopenhagenUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- 1 Jan 2017 (actual)
- Primary completion
- 31 Mar 2020 (estimated)
- Study completion
- 31 Mar 2020 (estimated)
- First posted
- 20 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Traditional paraclinical measures of disease severity in multiple sclerosis (MS), such as T2 lesion load as measured by magnetic resonance imaging (MRI), are poorly correlated with long-term disability accumulation. Other surrogate markers of the current and future disease burden are therefore needed. The permeability of the blood-brain-barrier (BBB) seems to better reflect the substantial, subclinical disease activity underlying MS progression. Its useful role as a prognostic marker in MS has been clearly established by the recent observation that BBB permeability increase in optic neuritis patients is associated with conversion to definite MS. BBB permeability can be quantified, in a convenient manner to the patient, using Dynamic-Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) by modelling the change in intrinsic MRI parameters of the human brain in response to the administration of a bolus contrast agent. Alemtuzumab is a disease modifying drug that depletes T- and B-cells. It is administered in two series separated by 12 months, as explained in the section "Groups and Interventions." The number of relapses are significantly reduced as compared to other efficacious treatments in MS, as demonstrated recently (study referred to by its ClinicalTrials.gov identifier NCT00050778). The efficacy of alemtuzumab in resolving the inflammatory burden underlying relapses is, thus, well-established. Its influence on subclinical inflammation, however, remains unknown. It is the aim of the present study to investigate whether or not the latter influence is of importance, and, consequently, can be used to evaluate the need for an intensified treatment, in the form of an additional series of alemtuzumab administration.
BBB permeability changes, as surrogate markers of subclinical inflammation, are measured every 6 months just prior to and during the course of alemtuzumab treatment. In order to elucidate other potential mechanisms involved in disability accumulation, biomarkers and MRI-derived parameters are evaluated concomitantly. Specifically, the role of metabolic changes are investigated using MRI methods that measures blood perfusion and oxygen consumption. Secondarily, the BBB permeability and metabolic changes are correlated to novel biomarkers of inflammation and neurodegeneration in serum and urine, as well as conventional measures of MS severity: annual relapse rate, Expanded Disability Severity Score, MRI-derived estimates of disease activity and brain atrophy.
35 patients are included in the study in order to achieve enough statistical power and accommodate drop-outs. Patients are MRI scanned at baseline, 6 months after alemtuzumab treatment, and, finally, prior to administration of the second series of alemtuzumab 12 months after the baseline MRI scanning. At each time point, the patient's disease status is evaluated by an experienced neurologist, and urine and serum samples are obtained. Repeated Measures Analysis Of Variance (ANOVA) will be used to evaluate changes of permeability of the BBB and metabolic parameters at different time points, and baseline characteristics, such as prednisolone treatment will be implemented as between-subjects covariates. Logistic regression will be applied to estimate the ability of BBB permeability changes to predict the need for additional series of alemtuzumab administration.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Alemtuzumab treated MS patients | – | Drug: AlemtuzumabThose with Multiple Sclerosis that have commenced therapy with alemtuzumab (60 mg infusion over the course of 5 days) and completed treatment with alemtuzumab (additional 36 mg infusion during the course of 3 days, 12 months later). |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Patients are recruited from the two dedicated MS clinics in the secondary health care sector of the danish capital region.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlemtuzumabAlso: LemtradaAlemtuzumab is administered to eligible patients in accordance with established treatment regimes. Initially 60 mg of alemtuzumab is injected intravenously over the course of 5 days. The first treatment series is followed by the injection of 36 mg of alemtuzumab over the course of 3 days 12 months later. During both drug interventions, the transient exacerbation in disease severity is alleviated by concomitant steroid therapy. | Drug | Alemtuzumab treated MS patients |
Primary outcome
Blood-Brain-Barrier Permeability
Time frame: 1 year
Blood-Brain-Barrier Permeability as measured by Dynamic-Contrast-Enhanced MRI (DCE-MRI)
9 secondary outcomes
Oxygen Consumption
Time frame: 1 year
Cerebral perfusion
Time frame: 1 year
Diffusion Tensor MRI parameters and MR spectroscopy metabolite concentrations
Time frame: 1 year
Brain atrophy
Time frame: 2 years
Clinical Severity of Disease
Time frame: 1 year
Relapse frequency
Time frame: 1 year
Plasma markers of Blood-Brain-Barrier breakdown
Time frame: 1 year
Plasma markers of neuronal damage
Time frame: 1 year
Urinary markers of inflammation
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2017.
- Background: PubMed 12045719Barkhof 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: PubMed 25074746Cramer 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: PubMed 15016008Broholm 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: PubMed 26187333Cramer 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: PubMed 21683931D'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: PubMed 19204160Gauthier 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: PubMed 22252237Ge 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: PubMed 18594554De 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: PubMed 2255233Larsson 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: PubMed 19780145Larsson 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.
- Background: PubMed 15163806Law M, Saindane AM, Ge Y, Babb JS, Johnson G, Mannon LJ, Herbert J, Grossman RI. Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology. 2004 Jun;231(3):645-52. doi: 10.1148/radiol.2313030996.
- Background: PubMed 26304148Naismith RT, Cross AH. Enhancing our understanding of white matter changes in early multiple sclerosis. Brain. 2015 Sep;138(Pt 9):2465-6. doi: 10.1093/brain/awv196. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henrik BW Larsson, MD, Prof. study director
Functional Imaging Unit, Department of Clinical Physiology, Nuclear medicine and PET, Glostrup Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by Glostrup University Hospital, Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peter F Svane, MD (93906653 ext. 45, peter.frederiksen.svane@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood-Brain-Barrier Permeability (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03193086, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2017.