Multiple SclerosisNCT01555684
Functional Changes Following Percutaneous Venoplasty in Multiple Sclerosis Patients
A study testing percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency in people with Multiple Sclerosis and Chronic Cerebrospinal Venous Insufficiency, run by University of Stirling at 1 site in United Kingdom.
Trial summary
Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that often results in reduced muscle function which produces fatigue, weakness and a decline in daily mobility. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis, Chronic Cerebrospinal Venous Insufficiency
- What is being tested?
- percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2012to Dec 2012
- Phase
- Interventional
- 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
Who may be able to join
- diagnosis of CCSVI using transcranial and extracranial colour Doppler sonography in both supine and sitting positions. The diagnosis requires that 2 or more of the following 5 criteria are met:
- reflux in the internal jugular or vertebral veins, or both, with the head in any position
- reflux in the deep cerebral veins
- high-resolution B-mode evidence of internal jugular vein stenosis
- absence of Doppler-detectable flow in the internal jugular veins and/or vertebral veins
- loss of postural control of the main cerebral venous outflow pathways.
Who cannot join
- non ambulatory
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Percutaneous Venoplasty on Muscular Function, Mobility and Fatigue of Multiple Sclerosis (MS) Patients With Chronic Cerebrospinal Venous Insufficiency (CCSVI).
Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that often results in reduced muscle function which produces fatigue, weakness and a decline in daily mobility. Although the underlying cause of the disease is unknown a possible contributory mechanism is chronic cerebrospinal venous insufficiency (CCSVI). Post-mortem studies and magnetic resonance venography have shown a strong relationship between the cerebral venous system and MS cortical plaques. From this a role for CCSVI in MS has been suggested: venous malformations that result in venous hypertension, pressure on the blood brain barrier and subsequent inflammation due to leakage of haemosiderin into the parenchyma. This provokes an immune response which results in neurodegeneration. A procedure known as percutaneous venoplasty whereupon a balloon is inserted and inflated into the jugular vein has been developed to improve this drainage of the CNS, reduce venous hypertension and improve symptoms associated with MS. Although this procedure is widely practiced throughout the world it has yet to be fully accepted as it needs to be supported by evidence based clinical trials. As such NHS National Institute for Health and Clinical Excellence (NICE) recently issued a consultation document to determine more about the procedure's clinical safety and efficacy. A common concern raised is the ability to prevent any possible placebo effect and like any other clinical trial should offer a sham procedure to a matched control group. The difficulty with this option are the ethical issues associated with an invasive sham treatment and also the practical issues of masking a potentially painful treatment such as venoplasty. One option is to have blinded neurological assessment of patients who have either been treated with venoplasty or had no active treatment. Another option is to use dependent measures that are unaffected by motivational or psychological influences which avoids any placebo effect issue. One such dependent measure is motor unit firing behaviour whilst contracting at a submaximal target force. Typically clinicians have used this to manage motor disorder patients but have used cumbersome invasive technology that can only measure a few motor units with limited accuracy. However, De Luca et al recently developed a high density surface electromyographic (HDsEMG) system that can measure 30-40 motor units with 92-97% accuracy. From this it has been proposed as a highly effective tool for evaluating efficacy of therapeutic interventions for upper motoneuron disorders such as MS.
Accordingly the investigators propose to use a repeated measures design on an experimental (receiving venoplasty) and control (not receiving venoplasty) MS groups (6 patients in each group) to determine the effect of the treatment on muscular function, mobility and fatigue. This would be combined with independent blinded neurological assessment of the two groups of patients.
Read more
This design enables us to achieve two aims:
- Acute neuromuscular response to the treatment
- Chronic response to the treatment (6 weeks) to determine the effect on muscular function, mobility and fatigue.*
Methods
- Four (first two to establish baseline variability of measures) repeat visits to the laboratory at University of Stirling to establish neuromuscular measures:
- HDsEMG pre and post tetanic induced fatigue
- Muscle fibre conduction velocity as previously described (Hunter et al., 2011)
- Ultrasound for CCSVI determination on visits 1 and 3
- DEXA scans for alterations in body composition on visits 2 and 4
- With the use of accelerometers monitor free living activity on days 0-7 and 9-42 (post venoplasty).
- Being tested
- percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency
- Keywords
- MS, CCSVI
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiencyProcedure or surgery
percutaneous venoplasty is where a balloon is inserted and inflated into the jugular vein has been developed to improve this drainage of the CNS, reduce venous hypertension and improve symptoms associated with MS
| Study group | Role | What they receive |
|---|---|---|
| venoplasty proceedures | Experimental | Half of the participants receive treatment and the other half do not Receives: Procedure: percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency |
| Control - no treatment | Placebo comparator | Not described Receives: Procedure: percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuromuscular function
The venoplasty procedure will be performed at 8 days
Measured: 52 days
Secondary outcomes (1)
Free living activity
Measured by accelerometery
Measured: 0-7 and 9-52 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2012 (estimated)
- Study startApr 2012
- Primary completionNov 2012
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Stirling
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr Angus Hunter, University of Stirling
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01555684
- Sponsor's protocol ID
- SPREC#501
- Status last verified
- Dec 2015
- First submitted
- 8 Mar 2012
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
De Luca CJ, Hostage EC. Relationship between firing rate and recruitment threshold of motoneurons in voluntary isometric contractions. J Neurophysiol. 2010 Aug;104(2):1034-46. doi: 10.1152/jn.01018.2009. Epub 2010 Jun 16.
PubMed 20554838Fog T. The topography of plaques in multiple sclerosis with special reference to cerebral plaques. Acta Neurol Scand Suppl. 1965;15:1-161. No abstract available.
PubMed 5213727Fox RJ, Rae-Grant A. Chronic cerebrospinal venous insufficiency: have we found the cause and cure of MS? Neurology. 2011 Jul 12;77(2):98-100. doi: 10.1212/WNL.0b013e318212a915. Epub 2011 Apr 13. No abstract available.
PubMed 21490321Ge Y, Zohrabian VM, Grossman RI. Seven-Tesla magnetic resonance imaging: new vision of microvascular abnormalities in multiple sclerosis. Arch Neurol. 2008 Jun;65(6):812-6. doi: 10.1001/archneur.65.6.812.
PubMed 18541803Hunter A, Albertus-Kajee Y, St Clair Gibson A. The effect of exercise induced hyperthermia on muscle fibre conduction velocity during sustained isometric contraction. J Electromyogr Kinesiol. 2011 Oct;21(5):834-40. doi: 10.1016/j.jelekin.2011.06.002. Epub 2011 Jul 13.
PubMed 21745750Kermode AG, Thompson AJ, Tofts P, MacManus DG, Kendall BE, Kingsley DP, Moseley IF, Rudge P, McDonald WI. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain. 1990 Oct;113 ( Pt 5):1477-89. doi: 10.1093/brain/113.5.1477.
PubMed 2245307Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T. Cortical lesions in multiple sclerosis. Brain. 1999 Jan;122 ( Pt 1):17-26. doi: 10.1093/brain/122.1.17.
PubMed 10050891Nawab SH, Chang SS, De Luca CJ. High-yield decomposition of surface EMG signals. Clin Neurophysiol. 2010 Oct;121(10):1602-15. doi: 10.1016/j.clinph.2009.11.092. Epub 2010 Apr 28.
PubMed 20430694Tan IL, van Schijndel RA, Pouwels PJ, van Walderveen MA, Reichenbach JR, Manoliu RA, Barkhof F. MR venography of multiple sclerosis. AJNR Am J Neuroradiol. 2000 Jun-Jul;21(6):1039-42.
PubMed 10871010Imperial College CCSVI Investigation Group; Thapar A, Lane TR, Pandey V, Shalhoub J, Malik O, Ellis M, Franklin IJ, Nicholas R, Davies AH. Internal jugular thrombosis post venoplasty for chronic cerebrospinal venous insufficiency. Phlebology. 2011 Sep;26(6):254-6. doi: 10.1258/phleb.2011.011052. Epub 2011 Jul 29.
PubMed 21803799Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Tacconi G, Dall'Ara S, Bartolomei I, Salvi F. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):392-9. doi: 10.1136/jnnp.2008.157164. Epub 2008 Dec 5.
PubMed 19060024Zamboni P, Menegatti E, Weinstock-Guttman B, Dwyer MG, Schirda CV, Malagoni AM, Hojnacki D, Kennedy C, Carl E, Bergsland N, Magnano C, Bartolomei I, Salvi F, Zivadinov R. Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report. BMC Med. 2011 Mar 7;9:22. doi: 10.1186/1741-7015-9-22.
PubMed 21385345
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
- The Effect of Percutaneous Venoplasty on Muscular Function, Mobility and Fatigue of Multiple Sclerosis (MS) Patients With Chronic Cerebrospinal Venous Insufficiency (CCSVI).
- ClinicalTrials.gov ID
- NCT01555684
- Acronym / sponsor ID
- SPREC#501
- Keywords
- MS, CCSVI
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of StirlingUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Nov 2012 (actual)
- Study completion
- Dec 2012 (estimated)
- First posted
- 15 Mar 2012 (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.
Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) that often results in reduced muscle function which produces fatigue, weakness and a decline in daily mobility. Although the underlying cause of the disease is unknown a possible contributory mechanism is chronic cerebrospinal venous insufficiency (CCSVI). Post-mortem studies and magnetic resonance venography have shown a strong relationship between the cerebral venous system and MS cortical plaques. From this a role for CCSVI in MS has been suggested: venous malformations that result in venous hypertension, pressure on the blood brain barrier and subsequent inflammation due to leakage of haemosiderin into the parenchyma. This provokes an immune response which results in neurodegeneration. A procedure known as percutaneous venoplasty whereupon a balloon is inserted and inflated into the jugular vein has been developed to improve this drainage of the CNS, reduce venous hypertension and improve symptoms associated with MS. Although this procedure is widely practiced throughout the world it has yet to be fully accepted as it needs to be supported by evidence based clinical trials. As such NHS National Institute for Health and Clinical Excellence (NICE) recently issued a consultation document to determine more about the procedure's clinical safety and efficacy. A common concern raised is the ability to prevent any possible placebo effect and like any other clinical trial should offer a sham procedure to a matched control group. The difficulty with this option are the ethical issues associated with an invasive sham treatment and also the practical issues of masking a potentially painful treatment such as venoplasty. One option is to have blinded neurological assessment of patients who have either been treated with venoplasty or had no active treatment. Another option is to use dependent measures that are unaffected by motivational or psychological influences which avoids any placebo effect issue. One such dependent measure is motor unit firing behaviour whilst contracting at a submaximal target force. Typically clinicians have used this to manage motor disorder patients but have used cumbersome invasive technology that can only measure a few motor units with limited accuracy. However, De Luca et al recently developed a high density surface electromyographic (HDsEMG) system that can measure 30-40 motor units with 92-97% accuracy. From this it has been proposed as a highly effective tool for evaluating efficacy of therapeutic interventions for upper motoneuron disorders such as MS.
Accordingly the investigators propose to use a repeated measures design on an experimental (receiving venoplasty) and control (not receiving venoplasty) MS groups (6 patients in each group) to determine the effect of the treatment on muscular function, mobility and fatigue. This would be combined with independent blinded neurological assessment of the two groups of patients.
This design enables us to achieve two aims:
- Acute neuromuscular response to the treatment
- Chronic response to the treatment (6 weeks) to determine the effect on muscular function, mobility and fatigue.*
Methods
- Four (first two to establish baseline variability of measures) repeat visits to the laboratory at University of Stirling to establish neuromuscular measures:
- HDsEMG pre and post tetanic induced fatigue
- Muscle fibre conduction velocity as previously described (Hunter et al., 2011)
- Ultrasound for CCSVI determination on visits 1 and 3
- DEXA scans for alterations in body composition on visits 2 and 4
- With the use of accelerometers monitor free living activity on days 0-7 and 9-42 (post venoplasty).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| venoplasty proceedures | Experimental | Procedure: percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiencyHalf of the participants receive treatment and the other half do not |
| Control - no treatment | Placebo comparator | Procedure: percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- diagnosis of CCSVI using transcranial and extracranial colour Doppler sonography in both supine and sitting positions. The diagnosis requires that 2 or more of the following 5 criteria are met:
Key exclusion criteria (1 listed)
- non ambulatory
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 |
|---|---|---|
| percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiencypercutaneous venoplasty is where a balloon is inserted and inflated into the jugular vein has been developed to improve this drainage of the CNS, reduce venous hypertension and improve symptoms associated with MS | Procedure or surgery | Control - no treatment, venoplasty proceedures |
Primary outcome
Neuromuscular function
Time frame: 52 days
The venoplasty procedure will be performed at 8 days
1 secondary outcome
Free living activity
Time frame: 0-7 and 9-52 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
- Background: PubMed 20554838De Luca CJ, Hostage EC. Relationship between firing rate and recruitment threshold of motoneurons in voluntary isometric contractions. J Neurophysiol. 2010 Aug;104(2):1034-46. doi: 10.1152/jn.01018.2009. Epub 2010 Jun 16.
- Background: PubMed 5213727Fog T. The topography of plaques in multiple sclerosis with special reference to cerebral plaques. Acta Neurol Scand Suppl. 1965;15:1-161. No abstract available.
- Background: PubMed 21490321Fox RJ, Rae-Grant A. Chronic cerebrospinal venous insufficiency: have we found the cause and cure of MS? Neurology. 2011 Jul 12;77(2):98-100. doi: 10.1212/WNL.0b013e318212a915. Epub 2011 Apr 13. No abstract available.
- Background: PubMed 18541803Ge Y, Zohrabian VM, Grossman RI. Seven-Tesla magnetic resonance imaging: new vision of microvascular abnormalities in multiple sclerosis. Arch Neurol. 2008 Jun;65(6):812-6. doi: 10.1001/archneur.65.6.812.
- Background: PubMed 21745750Hunter A, Albertus-Kajee Y, St Clair Gibson A. The effect of exercise induced hyperthermia on muscle fibre conduction velocity during sustained isometric contraction. J Electromyogr Kinesiol. 2011 Oct;21(5):834-40. doi: 10.1016/j.jelekin.2011.06.002. Epub 2011 Jul 13.
- Background: PubMed 2245307Kermode AG, Thompson AJ, Tofts P, MacManus DG, Kendall BE, Kingsley DP, Moseley IF, Rudge P, McDonald WI. Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain. 1990 Oct;113 ( Pt 5):1477-89. doi: 10.1093/brain/113.5.1477.
- Background: PubMed 10050891Kidd D, Barkhof F, McConnell R, Algra PR, Allen IV, Revesz T. Cortical lesions in multiple sclerosis. Brain. 1999 Jan;122 ( Pt 1):17-26. doi: 10.1093/brain/122.1.17.
- Background: PubMed 20430694Nawab SH, Chang SS, De Luca CJ. High-yield decomposition of surface EMG signals. Clin Neurophysiol. 2010 Oct;121(10):1602-15. doi: 10.1016/j.clinph.2009.11.092. Epub 2010 Apr 28.
- Background: PubMed 10871010Tan IL, van Schijndel RA, Pouwels PJ, van Walderveen MA, Reichenbach JR, Manoliu RA, Barkhof F. MR venography of multiple sclerosis. AJNR Am J Neuroradiol. 2000 Jun-Jul;21(6):1039-42.
- Background: PubMed 21803799Imperial College CCSVI Investigation Group; Thapar A, Lane TR, Pandey V, Shalhoub J, Malik O, Ellis M, Franklin IJ, Nicholas R, Davies AH. Internal jugular thrombosis post venoplasty for chronic cerebrospinal venous insufficiency. Phlebology. 2011 Sep;26(6):254-6. doi: 10.1258/phleb.2011.011052. Epub 2011 Jul 29.
- Background: PubMed 19060024Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Tacconi G, Dall'Ara S, Bartolomei I, Salvi F. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):392-9. doi: 10.1136/jnnp.2008.157164. Epub 2008 Dec 5.
- Background: PubMed 21385345Zamboni P, Menegatti E, Weinstock-Guttman B, Dwyer MG, Schirda CV, Malagoni AM, Hojnacki D, Kennedy C, Carl E, Bergsland N, Magnano C, Bartolomei I, Salvi F, Zivadinov R. Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report. BMC Med. 2011 Mar 7;9:22. doi: 10.1186/1741-7015-9-22.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency in people with Multiple Sclerosis and Chronic Cerebrospinal Venous Insufficiency, run by University of Stirling 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 6 inclusion and 1 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: withdrawn, 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. Some participants in this study may receive a placebo. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Neuromuscular function (time frame: 52 days). 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 NCT01555684, which also lists 12 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.