Multiple SclerosisSTAR-MSNCT02485223
Single Test to ARrive at MS Diagnosis. Using a Single MRI Brain Scan to Help Diagnose Multiple Sclerosis
An observational study of Multiple Sclerosis, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
This is a pilot study (a small scale study testing procedures so that the investigators can apply this to a larger scale study). This study will test the accuracy of a new brain scan (Magnetic Resonance Imaging) technique in predicting the diagnosis of multiple sclerosis (MS) in patients where there is uncertainty… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Sclerosis
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2015to May 2017
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The investigators will recruit patients who attend the general neurology and MS clinics at Nottingham University Hospitals (NUH) NHS Trust, UK. The researchers anticipate that the study population will comprise of two groups: the common presentation of young individuals following the first neurological symptoms suggestive of MS, however the neuroradiologist's report of the MRI will not be in agreement with the neurological impression; and a group of patients who present with atypical symptoms for MS but the MRI scan is reported as suggestive of MS.
Who may be able to join
- Able to tolerate an MRI brain scan
- No contraindications to MRI
- Radiological suspicion of MS, but clinically atypical or Clinical suspicion of MS, but radiologically atypical
- Radiological or clinical suspicion of any of the following with a routine MRI brain scan showing white matter lesions; Autoimmune/Inflammatory; Antiphospholipid syndrome, Neurosarcoidosis, Neuro-Behcet's disease, Neuromyelitis Optica, Systemic lupus erythematosus, Primary CNS vasculitis, Secondary CNS vasculitis, Sjogren's syndrome, Susac syndrome. Ischaemic; Hypertensive ischaemic disease (small vessel disease), embolic disease. Infective ; Lyme disease, Cytomegalovirus CNS infection, Toxocariasis, Neurocysticercosis, Whipple's disease, Progressive Multifocal Leukoencephalopathy, Herpes virus (HHV) infection e.g VZV, HIV, Toxoplasmosis, Tuberculosis, Neurosyphilis. Neoplastic; Lymphoma, Glioma, Primary CNS Lymphoma, Cerebral metastases. Other; CADASIL, Histiocytosis, Migraine, Mitochondrial disease, Leukodystrophy.
Who cannot join
- Unable to tolerate a further MRI scan
- Unsafe to perform an MRI scan
- Pregnancy
- Participants with normal routine clinical scans
- Unable to give written informed consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham, UK
Nottingham, Nottinghamshire, NG7 2UH
About this study
Official title: Single Test to ARrive at MS Diagnosis. A Prospective, Longitudinal, Investigator Blinded, Pilot Study Assessing the Accuracy of a Single 3 Tesla MRI Scan in Predicting Multiple Sclerosis in Cases of Diagnostic Uncertainty
This is a pilot study (a small scale study testing procedures so that the investigators can apply this to a larger scale study). This study will test the accuracy of a new brain scan (Magnetic Resonance Imaging) technique in predicting the diagnosis of multiple sclerosis (MS) in patients where there is uncertainty about the diagnosis. For patients where there is a suspicion (but not definite) diagnosis of MS, an additional MRI brain scan will be offered. There will be no other research tests and the patient is followed up to see what the eventual diagnosis is. The investigators will then review the original brain scan to see if this predicted the diagnosis of MS or not.
Read the detailed description
There is no single, simple test to differentiate MS from conditions that mimic it. Apart from the patient's symptoms, doctors use Magnetic Resonance Imaging (MRI) of the brain to see if there are abnormalities which are consistent with MS. In patients without typical symptoms or a typical MRI appearance, a firm diagnosis cannot be made as other neurological illnesses can mimic symptoms of MS and the MRI scans can look very similar. Further tests are often required such as lumbar punctures, resulting in delays, discomfort for the patient and additional healthcare costs. With time the diagnosis can become clearer as patients may develop other symptoms of MS but this may take months or years.
The most common errors are from misinterpretation of the brain abnormalities or 'lesions' seen on the MRI scan. Subsequently if a patient is misdiagnosed with MS they may receive treatment they do not need. Furthermore a delay in a firm diagnosis delays treatment for another condition. With the rapid increase of new medications in the last few years, accurate and rapid diagnosis is paramount.
Pathologically (when looking at lesions using a microscope) MS lesions usually have a vein running through the centre, whereas in lesions arising from other conditions, the investigators hypothesize that no central vein is seen. The investigators can therefore distinguish between patients with MS and patients without it.
The researchers therefore want to test the value of a clinical 3-Tesla MRI brain scan in accurately distinguishing between MS and other conditions, with MRI sequences that have been refined over the last few years.
Patients will only have one research MRI brain scan and then be followed up by their neurologist, who will confirm the final diagnosis. The investigators shall then look back at the original scans to see if those with MS had veins within their lesions and if those without MS had lesions without veins
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, MS, Diagnostic test, Central veins, MRI
- Medical subject headings
- Multiple Sclerosis
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in the proportion of central veins:lesions in patients with MS and non-MS.
To detect this difference with an alpha of 0.05 and power of 0.8, (based on previous data that shows a mean proportion of approx. 60% in MS patients and 6% in ischaemic patients) we will need 12 patients with MS and 12 with non-MS at 1 year of follow up. However given the fact that approx. 40% of patients will have a diagnosis of MS at 1 year, we will need to scan 60 patients in total.
Measured: After 1 year of follow up with a confirmed diagnosis.
Secondary outcomes (7)
Sensitivity of using a proportion of central veins:lesions in diagnosing MS.
Measured: After 1 year of follow up with a confirmed diagnosis
Specificity of using a proportion of central veins:lesions in diagnosing MS.
Measured: After 1 year of follow up with a confirmed diagnosis
Positive predictive value of the central vein:lesion MRI test.
Measured: After 1 year of follow up with a confirmed diagnosis
Negative predictive value of the central vein:lesion MRI test.
Measured: After 1 year of follow up with a confirmed diagnosis
Optimal proportion of central veins:lesions to make a diagnosis of MS.
Receiver Operating Characteristic (ROC) curves will be used.
Measured: After 1 year of follow up with a confirmed diagnosis.
Rate of patient recruitment.
Measured: After 1 year
Cohen's kappa inter-rater agreement for the diagnosis of MS using the MRI test.
Can different observers calculate the same proportion of central veins:lesions on each scan.
Measured: After 1 year of follow up.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2015 (estimated)
- Study startMay 2015
- Primary completionMay 2016 (estimated)
- Study completionMay 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dr Nikos Evangelou, MD, Principal investigator, Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02485223
- Sponsor's protocol ID
- 15022 [Sponsor reference]
- Other IDs
- 15/NW/0286
- Acronym
- STAR-MS
- Status last verified
- Dec 2015
- First submitted
- 23 Apr 2015
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Tallantyre EC, Brookes MJ, Dixon JE, Morgan PS, Evangelou N, Morris PG. Demonstrating the perivascular distribution of MS lesions in vivo with 7-Tesla MRI. Neurology. 2008 May 27;70(22):2076-8. doi: 10.1212/01.wnl.0000313377.49555.2e. No abstract available.
PubMed 18505982Tallantyre EC, Dixon JE, Donaldson I, Owens T, Morgan PS, Morris PG, Evangelou N. Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions. Neurology. 2011 Feb 8;76(6):534-9. doi: 10.1212/WNL.0b013e31820b7630.
PubMed 21300968Mistry N, Dixon J, Tallantyre E, Tench C, Abdel-Fahim R, Jaspan T, Morgan PS, Morris P, Evangelou N. Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain. JAMA Neurol. 2013 May;70(5):623-8. doi: 10.1001/jamaneurol.2013.1405.
PubMed 23529352Sati P, George IC, Shea CD, Gaitan MI, Reich DS. FLAIR*: a combined MR contrast technique for visualizing white matter lesions and parenchymal veins. Radiology. 2012 Dec;265(3):926-32. doi: 10.1148/radiol.12120208. Epub 2012 Oct 16.
PubMed 23074257
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Test to ARrive at MS Diagnosis. A Prospective, Longitudinal, Investigator Blinded, Pilot Study Assessing the Accuracy of a Single 3 Tesla MRI Scan in Predicting Multiple Sclerosis in Cases of Diagnostic Uncertainty
- ClinicalTrials.gov ID
- NCT02485223
- Acronym / sponsor ID
- STAR-MS / 15022 [Sponsor reference]
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, MS, Diagnostic test, Central veins, MRI
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- May 2016 (estimated)
- Study completion
- May 2017 (estimated)
- First posted
- 30 Jun 2015 (estimated)
- 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.
This is a pilot study (a small scale study testing procedures so that the investigators can apply this to a larger scale study). This study will test the accuracy of a new brain scan (Magnetic Resonance Imaging) technique in predicting the diagnosis of multiple sclerosis (MS) in patients where there is uncertainty about the diagnosis. For patients where there is a suspicion (but not definite) diagnosis of MS, an additional MRI brain scan will be offered. There will be no other research tests and the patient is followed up to see what the eventual diagnosis is. The investigators will then review the original brain scan to see if this predicted the diagnosis of MS or not.
Detailed description
There is no single, simple test to differentiate MS from conditions that mimic it. Apart from the patient's symptoms, doctors use Magnetic Resonance Imaging (MRI) of the brain to see if there are abnormalities which are consistent with MS. In patients without typical symptoms or a typical MRI appearance, a firm diagnosis cannot be made as other neurological illnesses can mimic symptoms of MS and the MRI scans can look very similar. Further tests are often required such as lumbar punctures, resulting in delays, discomfort for the patient and additional healthcare costs. With time the diagnosis can become clearer as patients may develop other symptoms of MS but this may take months or years.
The most common errors are from misinterpretation of the brain abnormalities or 'lesions' seen on the MRI scan. Subsequently if a patient is misdiagnosed with MS they may receive treatment they do not need. Furthermore a delay in a firm diagnosis delays treatment for another condition. With the rapid increase of new medications in the last few years, accurate and rapid diagnosis is paramount.
Pathologically (when looking at lesions using a microscope) MS lesions usually have a vein running through the centre, whereas in lesions arising from other conditions, the investigators hypothesize that no central vein is seen. The investigators can therefore distinguish between patients with MS and patients without it.
The researchers therefore want to test the value of a clinical 3-Tesla MRI brain scan in accurately distinguishing between MS and other conditions, with MRI sequences that have been refined over the last few years.
Patients will only have one research MRI brain scan and then be followed up by their neurologist, who will confirm the final diagnosis. The investigators shall then look back at the original scans to see if those with MS had veins within their lesions and if those without MS had lesions without veins
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The investigators will recruit patients who attend the general neurology and MS clinics at Nottingham University Hospitals (NUH) NHS Trust, UK. The researchers anticipate that the study population will comprise of two groups: the common presentation of young individuals following the first neurological symptoms suggestive of MS, however the neuroradiologist's report of the MRI will not be in agreement with the neurological impression; and a group of patients who present with atypical symptoms for MS but the MRI scan is reported as suggestive of MS.
Key inclusion criteria (4 listed)
- Able to tolerate an MRI brain scan
- No contraindications to MRI
- Radiological suspicion of MS, but clinically atypical or Clinical suspicion of MS, but radiologically atypical
- Radiological or clinical suspicion of any of the following with a routine MRI brain scan showing white matter lesions; Autoimmune/Inflammatory; Antiphospholipid syndrome, Neurosarcoidosis, Neuro-Behcet's disease, Neuromyelitis Optica, Systemic lupus erythematosus, Primary CNS vasculitis, Secondary CNS vasculitis, Sjogren's syndrome, Susac syndrome. Ischaemic; Hypertensive ischaemic disease (small vessel disease), embolic disease. Infective ; Lyme disease, Cytomegalovirus CNS infection, Toxocariasis, Neurocysticercosis, Whipple's disease, Progressive Multifocal Leukoencephalopathy, Herpes virus (HHV) infection e.g VZV, HIV, Toxoplasmosis, Tuberculosis, Neurosyphilis. Neoplastic; Lymphoma, Glioma, Primary CNS Lymphoma, Cerebral metastases. Other; CADASIL, Histiocytosis, Migraine, Mitochondrial disease, Leukodystrophy.
Key exclusion criteria (5 listed)
- Unable to tolerate a further MRI scan
- Unsafe to perform an MRI scan
- Pregnancy
- Participants with normal routine clinical scans
- Unable to give written informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Difference in the proportion of central veins:lesions in patients with MS and non-MS.
Time frame: After 1 year of follow up with a confirmed diagnosis.
To detect this difference with an alpha of 0.05 and power of 0.8, (based on previous data that shows a mean proportion of approx. 60% in MS patients and 6% in ischaemic patients) we will need 12 patients with MS and 12 with non-MS at 1 year of follow up. However given the fact that approx. 40% of patients will have a diagnosis of MS at 1 year, we will need to scan 60 patients in total.
7 secondary outcomes
Sensitivity of using a proportion of central veins:lesions in diagnosing MS.
Time frame: After 1 year of follow up with a confirmed diagnosis
Specificity of using a proportion of central veins:lesions in diagnosing MS.
Time frame: After 1 year of follow up with a confirmed diagnosis
Positive predictive value of the central vein:lesion MRI test.
Time frame: After 1 year of follow up with a confirmed diagnosis
Negative predictive value of the central vein:lesion MRI test.
Time frame: After 1 year of follow up with a confirmed diagnosis
Optimal proportion of central veins:lesions to make a diagnosis of MS.
Time frame: After 1 year of follow up with a confirmed diagnosis.
Rate of patient recruitment.
Time frame: After 1 year
Cohen's kappa inter-rater agreement for the diagnosis of MS using the MRI test.
Time frame: After 1 year of follow up.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
- Background: PubMed 18505982Tallantyre EC, Brookes MJ, Dixon JE, Morgan PS, Evangelou N, Morris PG. Demonstrating the perivascular distribution of MS lesions in vivo with 7-Tesla MRI. Neurology. 2008 May 27;70(22):2076-8. doi: 10.1212/01.wnl.0000313377.49555.2e. No abstract available.
- Background: PubMed 21300968Tallantyre EC, Dixon JE, Donaldson I, Owens T, Morgan PS, Morris PG, Evangelou N. Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions. Neurology. 2011 Feb 8;76(6):534-9. doi: 10.1212/WNL.0b013e31820b7630.
- Background: PubMed 23529352Mistry N, Dixon J, Tallantyre E, Tench C, Abdel-Fahim R, Jaspan T, Morgan PS, Morris P, Evangelou N. Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain. JAMA Neurol. 2013 May;70(5):623-8. doi: 10.1001/jamaneurol.2013.1405.
- Background: PubMed 23074257Sati P, George IC, Shea CD, Gaitan MI, Reich DS. FLAIR*: a combined MR contrast technique for visualizing white matter lesions and parenchymal veins. Radiology. 2012 Dec;265(3):926-32. doi: 10.1148/radiol.12120208. Epub 2012 Oct 16.
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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.
Dr Nikos Evangelou, MD principal investigator
Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham, UK
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 University of Nottingham at 1 site in United Kingdom.
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 4 inclusion and 5 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 2 Dec 2015. 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 United Kingdom. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in the proportion of central veins:lesions in patients with MS and non-MS. (time frame: After 1 year of follow up with a confirmed diagnosis.). 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 NCT02485223, which also lists 4 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 2 Dec 2015.