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Functional Changes Following Percutaneous Venoplasty in Multiple Sclerosis Patients

Primary Purpose

Multiple Sclerosis, Chronic Cerebrospinal Venous Insufficiency

Status
Withdrawn
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency
Sponsored by
University of Stirling
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring MS, CCSVI

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • non ambulatory

Sites / Locations

  • University of Stirling

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

venoplasty proceedures

Control - no treatment

Arm Description

Half of the participants receive treatment and the other half do not

Outcomes

Primary Outcome Measures

Neuromuscular function
The venoplasty procedure will be performed at 8 days

Secondary Outcome Measures

Free living activity
Measured by accelerometery

Full Information

First Posted
March 8, 2012
Last Updated
December 1, 2015
Sponsor
University of Stirling
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1. Study Identification

Unique Protocol Identification Number
NCT01555684
Brief Title
Functional Changes Following Percutaneous Venoplasty in Multiple Sclerosis Patients
Official Title
The Effect of Percutaneous Venoplasty on Muscular Function, Mobility and Fatigue of Multiple Sclerosis (MS) Patients With Chronic Cerebrospinal Venous Insufficiency (CCSVI).
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Withdrawn
Study Start Date
April 2012 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
December 2012 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Stirling

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Chronic Cerebrospinal Venous Insufficiency
Keywords
MS, CCSVI

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
venoplasty proceedures
Arm Type
Experimental
Arm Description
Half of the participants receive treatment and the other half do not
Arm Title
Control - no treatment
Arm Type
Placebo Comparator
Intervention Type
Procedure
Intervention Name(s)
percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency
Intervention Description
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
Primary Outcome Measure Information:
Title
Neuromuscular function
Description
The venoplasty procedure will be performed at 8 days
Time Frame
52 days
Secondary Outcome Measure Information:
Title
Free living activity
Description
Measured by accelerometery
Time Frame
0-7 and 9-52 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: non ambulatory
Facility Information:
Facility Name
University of Stirling
City
Stirling
ZIP/Postal Code
FK94LA
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
20554838
Citation
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. Erratum In: J Neurophysiol. 2012 Mar;107(5):1544.
Results Reference
background
PubMed Identifier
5213727
Citation
Fog 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.
Results Reference
background
PubMed Identifier
21490321
Citation
Fox 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.
Results Reference
background
PubMed Identifier
18541803
Citation
Ge 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.
Results Reference
background
PubMed Identifier
21745750
Citation
Hunter 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.
Results Reference
background
PubMed Identifier
2245307
Citation
Kermode 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.
Results Reference
background
PubMed Identifier
10050891
Citation
Kidd 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.
Results Reference
background
PubMed Identifier
20430694
Citation
Nawab 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.
Results Reference
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PubMed Identifier
10871010
Citation
Tan 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.
Results Reference
background
PubMed Identifier
21803799
Citation
Imperial 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.
Results Reference
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PubMed Identifier
19060024
Citation
Zamboni 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.
Results Reference
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PubMed Identifier
21385345
Citation
Zamboni 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.
Results Reference
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Functional Changes Following Percutaneous Venoplasty in Multiple Sclerosis Patients

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