Multiple SclerosisDECISIveNCT04024969
DiagnosE Using the Central veIn SIgn
An observational study of Multiple Sclerosis, run by Nottingham University Hospitals NHS Trust at 4 sites in United Kingdom.
Trial summary
There is currently no agreement on the best way to diagnose Multiple Sclerosis (MS). Frequently, people suspected of having MS have a standard MRI scan and undergo a 'lumbar puncture' (a thin needle is inserted between the bones in the lower spine). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- T2* MRI and Lumbar puncture to test for presence of unmatched oligoclonal bands
- How many people
- 115 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- 6 Nov 2019to Nov 2022
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Most participants are expected to have been evaluated by a hospital doctor (usually neurologist or ophthalmologist) at the local site and referred for diagnostic testing to the local MS team.
Who may be able to join
- Aged 18 to 65 years.
- Presentation with a typical clinically isolated syndrome (Thompson et al. 2017) for diagnostic evaluation of MS.
Who cannot join
- Fulfils the diagnosis of MS, as defined by the 2017 revision of McDonald diagnostic criteria (Thompson et al. 2017).
- Unwilling or unable to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that, in the opinion of the PI, is likely to affect the participant's ability to comply with the study protocol.
- Unable to provide informed consent.
- Contraindication or inability to undergo MRI due to metal or metal implants, pregnancy, claustrophobia, pain, spasticity, or excessive movement related to tremor.
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites, 4 recruiting
- Recruiting
Cardiff & Vale University Lhb
Cardiff
Emma Tallantyre
- Recruiting
Barts Health Nhs Trust
London
Klaus Schmierer
- Recruiting
Nottingham University Hospitals NHS Trust
Nottingham
Nikos Evangelou
- Recruiting
Oxford University Hospitals Nhs Foundation Trust
Oxford
Matthew Craner
About this study
Official title: DECISIve - DiagnosE Using the Central veIn SIgn. A Prospective Diagnostic Superiority Study Comparing T2* MRI and Lumbar Puncture in Patients Presenting With Possible Multiple Sclerosis
There is currently no agreement on the best way to diagnose Multiple Sclerosis (MS). Frequently, people suspected of having MS have a standard MRI scan and undergo a 'lumbar puncture' (a thin needle is inserted between the bones in the lower spine). Patients often report they find it painful and it can cause unintended complications requiring hospitalisations or time off work to recover.
Although the fluid taken during a lumbar puncture can show evidence of disease, this is not always the case. Doctors do not find abnormalities in everyone who has MS but some people with conditions that can mimic MS, but need very different treatment, have similar lumbar puncture abnormalities. Both of these problems can lead to misdiagnosis.
Read more
A new MRI scan allows doctors to see small veins that run through damaged areas of the brain in people with MS. It has been shown that this is a specific finding to MS, seldom seen in other conditions. It is not painful and carries few or no risks.
This research aims to change the way people are diagnosed with MS and reduce the number of lumbar punctures used. The investigators will recruit a large number of people from different hospitals whose doctors suspect they may have MS. They will be invited to have the new eight-minute MRI scan. After 18 months, the investigators will find out what diagnosis is eventually reached and compare this to the finding of the new scan. The investigators will then compare the accuracy, speed, costs and acceptability of the different tests needed to make a diagnosis of MS and establish if most lumbar punctures can be replaced by a slightly longer MRI scan. This research could provide the National Health Service with a scientific approach to diagnose MS which is safer, more cost effective and importantly, more acceptable to patients.
Read the detailed description
The North American Imaging in MS Cooperative has reviewed the utility of the central vein sign (CVS) in the diagnosis of MS in 2015. They concluded that "To formally establish the clinical value of the CVS for the differential diagnosis at disease onset, a large, prospective, multicentre study including patients at first presentation of possible MS is necessary". The paper outlining the 2017 McDonald diagnostic criteria for MS specifically mentions the promise of the CVS but suggests that it "requires detailed investigation to determine whether it is useful and practical". The rationale of this study is to provide an overwhelming case for a straightforward and rapid clinical adoption of our MRI test, which will change our ability to confirm or refute the diagnosis of MS.
Radiologists and neurologists can also readily interpret our proposed CVS using a simple 'rule of six' that was described in a previous study. This involves the detection of any six lesions with a central vein present. This rule has the potential to be easily implemented in clinical practice if it has superior diagnostic sensitivity, when compared to lumbar puncture results.
If the CVS can be shown to have superior diagnostic sensitivity at first presentation of MS, when compared to performing a lumbar puncture, then lumbar punctures can be avoided in many patients. These patients will benefit in several ways. The patients will avoid a procedure that is often painful or unpleasant. Those who currently refuse to have lumbar puncture will benefit from expedited diagnosis, limiting their anxiety and uncertainty. A secure diagnosis could lead to more rapid treatment decisions and a better long-term prognosis. In addition, fewer workdays will be lost attending hospital for investigation. From the NHS' perspective, it would avoid day case hospital admissions for lumbar punctures and readmissions to treat the common complication of post lumbar puncture headaches. This would create significant cost savings, when considering the significant number of patients undergoing this diagnostic process.
- Conditions
- Multiple Sclerosis
- Being tested
- T2* MRI, Lumbar puncture to test for presence of unmatched oligoclonal bands
- Keywords
- Central Vein Sign, Translational Neuroimaging, Multiple Sclerosis
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T2* MRIDiagnostic test
Research T2* weighted MRI sequence
Lumbar puncture to test for presence of unmatched oligoclonal bandsDiagnostic test
Current clinical standard practice
| Study group | Role | What they receive |
|---|---|---|
| Clinically isolated syndrome | Those presenting for diagnositic evaluation of multiple sclerosis, not currently meeting the 2017 McDonald criteria. Receives: Diagnostic Test: T2* MRI; Diagnostic Test: Lumbar puncture to test for presence of unmatched oligoclonal bands |
What is being measured
The primary outcome is the main question the study is designed to answer.
The sensitivity of the central vein sign (CVS) on T2* MRI scan and lumbar puncture with oligoclonal band testing at diagnosing MS at the time of the patients' first presentation.
The reference standard for both tests will be clinical diagnosis 18 months after recruitment. The sensitivity of each test will be reported separately along with 95% confidence intervals. The sensitivity of the tests will be compared using McNemar's test for paired proportions.
Measured: 18 months
Secondary outcomes (2)
The specificity of the central vein sign (CVS) on T2* MRI scan and lumbar puncture with oligoclonal band testing at diagnosing MS at the time of the patients' first presentation.
The reference standard for both tests will be clinical diagnosis 18 months after recruitment. The specificity of each test will be reported separately along with 95% confidence intervals. The specificity of the tests will be compared using McNemar's test for paired proportions.
Measured: 18 months
The sensitivity and specificity of the 'rule of six' proposed in Mistry et al. 2016.
The reference standard for the test will be clinical diagnosis 18 months after recruitment. The sensitivity and specificity of the 'rule of six' test will be reported separately along with 95% confidence intervals. The sensitivity and specificity of the 'rule of six' against lumbar puncture result will be compared using McNemar's test for paired proportions.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2019
- Study start6 Nov 2019
- Primary completionMay 2022 (estimated)
- Study completionNov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- Other
- Time perspective
- Prospective
- Enrolment
- 115 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nottingham University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nikos Evangelou, MD, Principal investigator, Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04024969
- Sponsor's protocol ID
- 18GNS004
- Acronym
- DECISIve
- Status last verified
- Jul 2019
- First submitted
- 12 Jun 2019
- Last updated
- 4 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintore M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2. Epub 2017 Dec 21.
PubMed 29275977Mistry N, Abdel-Fahim R, Samaraweera A, Mougin O, Tallantyre E, Tench C, Jaspan T, Morris P, Morgan PS, Evangelou N. Imaging central veins in brain lesions with 3-T T2*-weighted magnetic resonance imaging differentiates multiple sclerosis from microangiopathic brain lesions. Mult Scler. 2016 Sep;22(10):1289-96. doi: 10.1177/1352458515616700. Epub 2015 Dec 10.
PubMed 26658816
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DECISIve - DiagnosE Using the Central veIn SIgn. A Prospective Diagnostic Superiority Study Comparing T2* MRI and Lumbar Puncture in Patients Presenting With Possible Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT04024969
- Acronym / sponsor ID
- DECISIve / 18GNS004
- Conditions
- Multiple Sclerosis
- Keywords
- Central Vein Sign, Translational Neuroimaging, Multiple Sclerosis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 115 participants (estimated)
- Lead sponsor
- Nottingham University Hospitals NHS TrustUniversity, hospital or other
- Study start
- 6 Nov 2019 (actual)
- Primary completion
- May 2022 (estimated)
- Study completion
- Nov 2022 (estimated)
- First posted
- 18 Jul 2019 (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.
There is currently no agreement on the best way to diagnose Multiple Sclerosis (MS). Frequently, people suspected of having MS have a standard MRI scan and undergo a 'lumbar puncture' (a thin needle is inserted between the bones in the lower spine). Patients often report they find it painful and it can cause unintended complications requiring hospitalisations or time off work to recover.
Although the fluid taken during a lumbar puncture can show evidence of disease, this is not always the case. Doctors do not find abnormalities in everyone who has MS but some people with conditions that can mimic MS, but need very different treatment, have similar lumbar puncture abnormalities. Both of these problems can lead to misdiagnosis.
A new MRI scan allows doctors to see small veins that run through damaged areas of the brain in people with MS. It has been shown that this is a specific finding to MS, seldom seen in other conditions. It is not painful and carries few or no risks.
This research aims to change the way people are diagnosed with MS and reduce the number of lumbar punctures used. The investigators will recruit a large number of people from different hospitals whose doctors suspect they may have MS. They will be invited to have the new eight-minute MRI scan. After 18 months, the investigators will find out what diagnosis is eventually reached and compare this to the finding of the new scan. The investigators will then compare the accuracy, speed, costs and acceptability of the different tests needed to make a diagnosis of MS and establish if most lumbar punctures can be replaced by a slightly longer MRI scan. This research could provide the National Health Service with a scientific approach to diagnose MS which is safer, more cost effective and importantly, more acceptable to patients.
Detailed description
The North American Imaging in MS Cooperative has reviewed the utility of the central vein sign (CVS) in the diagnosis of MS in 2015. They concluded that "To formally establish the clinical value of the CVS for the differential diagnosis at disease onset, a large, prospective, multicentre study including patients at first presentation of possible MS is necessary". The paper outlining the 2017 McDonald diagnostic criteria for MS specifically mentions the promise of the CVS but suggests that it "requires detailed investigation to determine whether it is useful and practical". The rationale of this study is to provide an overwhelming case for a straightforward and rapid clinical adoption of our MRI test, which will change our ability to confirm or refute the diagnosis of MS.
Radiologists and neurologists can also readily interpret our proposed CVS using a simple 'rule of six' that was described in a previous study. This involves the detection of any six lesions with a central vein present. This rule has the potential to be easily implemented in clinical practice if it has superior diagnostic sensitivity, when compared to lumbar puncture results.
If the CVS can be shown to have superior diagnostic sensitivity at first presentation of MS, when compared to performing a lumbar puncture, then lumbar punctures can be avoided in many patients. These patients will benefit in several ways. The patients will avoid a procedure that is often painful or unpleasant. Those who currently refuse to have lumbar puncture will benefit from expedited diagnosis, limiting their anxiety and uncertainty. A secure diagnosis could lead to more rapid treatment decisions and a better long-term prognosis. In addition, fewer workdays will be lost attending hospital for investigation. From the NHS' perspective, it would avoid day case hospital admissions for lumbar punctures and readmissions to treat the common complication of post lumbar puncture headaches. This would create significant cost savings, when considering the significant number of patients undergoing this diagnostic process.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clinically isolated syndrome | – | Diagnostic Test: T2* MRI, Diagnostic Test: Lumbar puncture to test for presence of unmatched oligoclonal bandsThose presenting for diagnositic evaluation of multiple sclerosis, not currently meeting the 2017 McDonald criteria. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Most participants are expected to have been evaluated by a hospital doctor (usually neurologist or ophthalmologist) at the local site and referred for diagnostic testing to the local MS team.
Key inclusion criteria (2 listed)
- Aged 18 to 65 years.
- Presentation with a typical clinically isolated syndrome (Thompson et al. 2017) for diagnostic evaluation of MS.
Key exclusion criteria (4 listed)
- Fulfils the diagnosis of MS, as defined by the 2017 revision of McDonald diagnostic criteria (Thompson et al. 2017).
- Unwilling or unable to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that, in the opinion of the PI, is likely to affect the participant's ability to comply with the study protocol.
- Unable to provide informed consent.
- Contraindication or inability to undergo MRI due to metal or metal implants, pregnancy, claustrophobia, pain, spasticity, or excessive movement related to tremor.
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 |
|---|---|---|
| T2* MRIResearch T2* weighted MRI sequence | Diagnostic test | Clinically isolated syndrome |
| Lumbar puncture to test for presence of unmatched oligoclonal bandsCurrent clinical standard practice | Diagnostic test | Clinically isolated syndrome |
Primary outcome
The sensitivity of the central vein sign (CVS) on T2* MRI scan and lumbar puncture with oligoclonal band testing at diagnosing MS at the time of the patients' first presentation.
Time frame: 18 months
The reference standard for both tests will be clinical diagnosis 18 months after recruitment. The sensitivity of each test will be reported separately along with 95% confidence intervals. The sensitivity of the tests will be compared using McNemar's test for paired proportions.
2 secondary outcomes
The specificity of the central vein sign (CVS) on T2* MRI scan and lumbar puncture with oligoclonal band testing at diagnosing MS at the time of the patients' first presentation.
Time frame: 18 months
The sensitivity and specificity of the 'rule of six' proposed in Mistry et al. 2016.
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Background: PubMed 29275977Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintore M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2. Epub 2017 Dec 21.
- Background: PubMed 26658816Mistry N, Abdel-Fahim R, Samaraweera A, Mougin O, Tallantyre E, Tench C, Jaspan T, Morris P, Morgan PS, Evangelou N. Imaging central veins in brain lesions with 3-T T2*-weighted magnetic resonance imaging differentiates multiple sclerosis from microangiopathic brain lesions. Mult Scler. 2016 Sep;22(10):1289-96. doi: 10.1177/1352458515616700. Epub 2015 Dec 10.
- Individual participant dataSharing planned: Undecided
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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.
Nikos Evangelou, MD principal investigator
Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham
4 sites 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 Nottingham University Hospitals NHS Trust at 4 sites 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 2 inclusion and 4 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 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Contact Research and Innovation (0115 924 9924, researchsponsor@nuh.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The sensitivity of the central vein sign (CVS) on T2* MRI scan and lumbar puncture with oligoclonal band testing at diagnosing MS at the time of the patients' first presentation. (time frame: 18 months). 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 NCT04024969, which also lists 2 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 4 Mar 2020.