Evaluation of Angioplasty in the Treatment of Chronic Cerebrospinal Venous Insufficiency (CCSVI) in Multiple Sclerosis

The Effectiveness of Endovascular Treatment of Chronic Cerebrospinal Venous Insufficiency (CCSVI) in Patients With Multiple Sclerosis

The study is being done to determine if venous angioplasty is an effective treatment for chronic cerebrospinal venous insufficiency (CCSVI). In this condition, areas of narrowing or blockages are present in the internal jugular or azygos veins (veins which drain blood from the central nervous system) and these blockages may be associated with symptoms classically attributed to MS. Therefore, angioplasty may help to improve the symptoms associated with CCSVI and multiple sclerosis (MS). In this study, the investigators will evaluate the effectiveness of angioplasty in the treatment of CCSVI by comparing two the outcomes of two groups of patients: one group with CCSVI diagnosed on a venogram and treated with angioplasty and one group with CCSVI diagnosed on a venogram but not treated. The patients enrolled in this study, and the neurologist evaluating patients after the procedure, will not know whether or not they were treated with angioplasty.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Procedure: Angioplasty; Other: Observation

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • Latham, New York, United States, 12110
      • Image Care Latham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who are willing to comply with the protocol requirements and can be contacted by telephone
• Patients 18-60 years of age
• Patients with clinically definite multiple sclerosis by Polman criteria
• Patients with a history of MS as defined above with an EDSS between 3-6.
• Patients with a significant stenosis of the internal jugular or azygos vein on the basis of magnetic resonance venography or Doppler ultrasound.

Exclusion Criteria:

• Patients with renal insufficiency based on an estimated GFR <45
• Patients with a known severe allergy to iodine or gadolinium-based contrast agents which cannot be adequately pre-medicated
• Patients with a known allergy to nickel
• Patients who pregnant
• Patients with a contraindication to anticoagulation or anti-platelet medication
• Patients with a contraindication to drugs used for conscious sedation during interventional procedures, including Versed and Fentanyl
• Patients with a history of deep venous thrombosis of the lower extremities
• Patients with occlusion of the right and left common femoral veins
• Patients who have had any changes in their disease modifying drug regimen for MS during the 6 months prior to enrollment in this trial. This would include the addition of any new medications, a change in the dosage of any medications, or the removal of any medications from a patient's drug regimen
• Patients with a life expectancy <18 months
• Patients who are currently enrolled or who plan to enroll in other investigations that conflict with follow-up testing or confounds data in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment of CCSVI with Angioplasty; At the time of venography, these patients will have had a significant lesion (blockage) in the internal jugular and/or the azygos vein that will be treated with angioplasty.	Procedure: Angioplasty; In this procedure, a small catheter (tube) that is approximately the size of a piece of spaghetti is introduced into the vein that is narrowed based on the findings of the venogram. This catheter has a small balloon on it. That balloon is inflated across the narrowing within the vein with the goal of increasing the diameter of that vein and improving flow within that vein.
Sham Comparator: Observation of CCSVI; At the time of venography, these patients will have had a significant lesion (blockage) in the internal jugular and/or the azygos vein that will not be treated with angioplasty. These patients will be observed after treatment and compared to those patients who received treatment.	Other: Observation; Patients in this arm will be diagnosed with CCSVI based on venography but will receive no intervention. They will be followed in the same manner as patients treated with angioplasty.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of CCSVI treatment on quality of life in patients with MS	This will be assessed using the Multiple Sclerosis Quality of Life-54 (MSQOL-54), which is a health-related quality of life measure that combines generic and MS-specific items into a single, self-report questionnaire.	1 Month
Impact of CCSVI treatment on quality of life in patients with MS	This will be assessed using the Multiple Sclerosis Quality of Life-54 (MSQOL-54), which is a health-related quality of life measure that combines generic and MS-specific items into a single, self-report questionnaire.	3 Months
Impact of CCSVI treatment on quality of life in patients with MS	This will be assessed using the Multiple Sclerosis Quality of Life-54 (MSQOL-54), which is a health-related quality of life measure that combines generic and MS-specific items into a single, self-report questionnaire.	6 Months
Impact of CCSVI treatment on quality of life in patients with MS	This will be assessed using the Multiple Sclerosis Quality of Life-54 (MSQOL-54), which is a health-related quality of life measure that combines generic and MS-specific items into a single, self-report questionnaire.	12 Months
Impact of CCSVI treatment on quality of life in patients with MS	This will be assessed using the Multiple Sclerosis Quality of Life-54 (MSQOL-54), which is a health-related quality of life measure that combines generic and MS-specific items into a single, self-report questionnaire.	18 Months
Impact of CCSVI treatment on quality of life in patients with MS	This will be assessed using the Multiple Sclerosis Quality of Life-54 (MSQOL-54), which is a health-related quality of life measure that combines generic and MS-specific items into a single, self-report questionnaire.	24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical significance of CCSVI in MS patients	This will be assessed clinically using annualized relapse rates, Expanded Disability Status Scale (EDSS) change and change in the timed 25 foot walk.	1 month
Superiority of angioplasty to observation for treatment of CCSVI	This will be assessed clinically using annualized relapse rates, EDSS change, and change in the timed 25-foot walk	1 month
Incidence of CCSVI in patients with MS	This will be assessed on the basis of the findings on diagnostic venography of the internal jugular and azygos veins, which is the initial procedure performed in these patients.	0 Months
Safety of endovascular treatment of CCSVI	This is defined as the number and nature of any procedure-related adverse effects	1 month
Target vessel primary and secondary patency	Primary patency is the interval following the initial angioplasty procedure until a reintervention is performed to preserve patency. Secondary patency is defined as the interval following the initial angioplasty procedure until treatment of the vein is abandoned due to an inability to treat the original lesion	1 month
Clinical significance of CCSVI in MS patients	This will be assessed clinically using annualized relapse rates, EDSS change and change in the timed 25 foot walk.	6 months
Clinical significance of CCSVI in MS patients	This will be assessed clinically using annualized relapse rates, EDSS change and change in the timed 25 foot walk.	12 months
Clinical significance of CCSVI in MS patients	This will be assessed clinically using annualized relapse rates, EDSS change and change in the timed 25 foot walk.	18 months
Clinical significance of CCSVI in MS patients	This will be assessed clinically using annualized relapse rates, EDSS change and change in the timed 25 foot walk.	24 months
Superiority of angioplasty to observation for treatment of CCSVI	This will be assessed clinically using annualized relapse rates, EDSS change, and change in the timed 25-foot walk	6 Months
Superiority of angioplasty to observation for treatment of CCSVI	This will be assessed clinically using annualized relapse rates, EDSS change, and change in the timed 25-foot walk	12 Months
Superiority of angioplasty to observation for treatment of CCSVI	This will be assessed clinically using annualized relapse rates, EDSS change, and change in the timed 25-foot walk	18 Months
Superiority of angioplasty to observation for treatment of CCSVI	This will be assessed clinically using annualized relapse rates, EDSS change, and change in the timed 25-foot walk	24 Months
Safety of endovascular treatment of CCSVI	This is defined as the number and nature of any procedure-related adverse effects	3 months
Safety of endovascular treatment of CCSVI	This is defined as the number and nature of any procedure-related adverse effects	6 months
Safety of endovascular treatment of CCSVI	This is defined as the number and nature of any procedure-related adverse effects	12 months
Safety of endovascular treatment of CCSVI	This is defined as the number and nature of any procedure-related adverse effects	18 months
Safety of endovascular treatment of CCSVI	This is defined as the number and nature of any procedure-related adverse effects	24 months
Target vessel primary and secondary patency	Primary patency is the interval following the initial angioplasty procedure until a reintervention is performed to preserve patency. Secondary patency is defined as the interval following the initial angioplasty procedure until treatment of the vein is abandoned due to an inability to treat the original lesion	3 months
Target vessel primary and secondary patency	Primary patency is the interval following the initial angioplasty procedure until a reintervention is performed to preserve patency. Secondary patency is defined as the interval following the initial angioplasty procedure until treatment of the vein is abandoned due to an inability to treat the original lesion	6 months
Target vessel primary and secondary patency	Primary patency is the interval following the initial angioplasty procedure until a reintervention is performed to preserve patency. Secondary patency is defined as the interval following the initial angioplasty procedure until treatment of the vein is abandoned due to an inability to treat the original lesion	12 months
Target vessel primary and secondary patency	Primary patency is the interval following the initial angioplasty procedure until a reintervention is performed to preserve patency. Secondary patency is defined as the interval following the initial angioplasty procedure until treatment of the vein is abandoned due to an inability to treat the original lesion	18 months
Target vessel primary and secondary patency	Primary patency is the interval following the initial angioplasty procedure until a reintervention is performed to preserve patency. Secondary patency is defined as the interval following the initial angioplasty procedure until treatment of the vein is abandoned due to an inability to treat the original lesion	24 months

Collaborators and Investigators

• Sponsor: Community Care Physicians, P.C.

Publications and helpful links

General Publications

• Zamboni P, Galeotti R, Menegatti E, Malagoni AM, Gianesini S, Bartolomei I, Mascoli F, Salvi F. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg. 2009 Dec;50(6):1348-58.e1-3. doi: 10.1016/j.jvs.2009.07.096. Erratum In: J Vasc Surg. 2010 Apr;51(4):1079.
• 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.
• Zamboni P, Menegatti E, Weinstock-Guttman B, Schirda C, Cox JL, Malagoni AM, Hojanacki D, Kennedy C, Carl E, Dwyer MG, Bergsland N, Galeotti R, Hussein S, Bartolomei I, Salvi F, Zivadinov R. The severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis is related to altered cerebrospinal fluid dynamics. Funct Neurol. 2009 Jul-Sep;24(3):133-8.
• Bartolomei I, Salvi F, Galeotti R, Salviato E, Alcanterini M, Menegatti E, Mascalchi M, Zamboni P. Hemodynamic patterns of chronic cerebrospinal venous insufficiency in multiple sclerosis. Correlation with symptoms at onset and clinical course. Int Angiol. 2010 Apr;29(2):183-8.
• Malagoni AM, Galeotti R, Menegatti E, Manfredini F, Basaglia N, Salvi F, Zamboni P. Is chronic fatigue the symptom of venous insufficiency associated with multiple sclerosis? A longitudinal pilot study. Int Angiol. 2010 Apr;29(2):176-82.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: September 10, 2010
• First Submitted That Met QC Criteria: September 14, 2010
• First Posted (Estimate): September 15, 2010

Study Record Updates

• Last Update Posted (Estimate): November 26, 2013
• Last Update Submitted That Met QC Criteria: November 25, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Vein; Angioplasty
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Venous Insufficiency
• Other Study ID Numbers: 2794