Functional Changes Following Percutaneous Venoplasty in Multiple Sclerosis Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2012 by University of Stirling.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by (Responsible Party):
Dr Angus Hunter, University of Stirling
ClinicalTrials.gov Identifier:
NCT01555684
First received: March 8, 2012
Last updated: March 13, 2012
Last verified: March 2012
  Purpose

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:

  1. Acute neuromuscular response to the treatment
  2. 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:

    1. HDsEMG pre and post tetanic induced fatigue
    2. Muscle fibre conduction velocity as previously described (Hunter et al., 2011)
    3. Ultrasound for CCSVI determination on visits 1 and 3
    4. 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).

Condition Intervention
Multiple Sclerosis
Chronic Cerebrospinal Venous Insufficiency
Procedure: percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Percutaneous Venoplasty on Muscular Function, Mobility and Fatigue of Multiple Sclerosis (MS) Patients With Chronic Cerebrospinal Venous Insufficiency (CCSVI).

Resource links provided by NLM:


Further study details as provided by University of Stirling:

Primary Outcome Measures:
  • Neuromuscular function [ Time Frame: 52 days ] [ Designated as safety issue: No ]
    The venoplasty procedure will be performed at 8 days


Secondary Outcome Measures:
  • Free living activity [ Time Frame: 0-7 and 9-52 days ] [ Designated as safety issue: No ]
    Measured by accelerometery


Estimated Enrollment: 12
Study Start Date: April 2012
Estimated Study Completion Date: August 2012
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: venoplasty proceedures
Half of the participants receive treatment and the other half do not
Procedure: percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency
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
Placebo Comparator: Control - no treatment Procedure: percutaneous venoplasty to alleviate chronic cerebrospinal venous insufficiency
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01555684

Contacts
Contact: Angus Hunter, PhD a.m.hunter1@stir.ac.uk

Locations
United Kingdom
University of Stirling
Stirling, United Kingdom, FK94LA
Sponsors and Collaborators
University of Stirling
  More Information

Publications:

Responsible Party: Dr Angus Hunter, Principal Investigator, University of Stirling
ClinicalTrials.gov Identifier: NCT01555684     History of Changes
Other Study ID Numbers: SPREC#501
Study First Received: March 8, 2012
Last Updated: March 13, 2012
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Stirling:
MS
CCSVI

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Venous Insufficiency
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 30, 2014