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

• ClinicalTrials.gov Identifier: NCT01201707
• Recruitment Status: Terminated
• First Posted: September 15, 2010
• Last Update Posted: November 26, 2013
• Sponsor: Community Care Physicians, P.C.
• Information provided by (Responsible Party): Gary Siskin, MD, Albany Medical College

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Procedure: Angioplasty; Other: Observation	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effectiveness of Endovascular Treatment of Chronic Cerebrospinal Venous Insufficiency (CCSVI) in Patients With Multiple Sclerosis
• Study Start Date: August 2010
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: September 2013

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Impact of CCSVI treatment on quality of life in patients with MS [ Time Frame: 1 Month ]
   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.
2. Impact of CCSVI treatment on quality of life in patients with MS [ Time Frame: 3 Months ]
   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. Impact of CCSVI treatment on quality of life in patients with MS [ Time Frame: 6 Months ]
   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.
4. Impact of CCSVI treatment on quality of life in patients with MS [ Time Frame: 12 Months ]
   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.
5. Impact of CCSVI treatment on quality of life in patients with MS [ Time Frame: 18 Months ]
   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. Impact of CCSVI treatment on quality of life in patients with MS [ Time Frame: 24 Months ]
   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.

Secondary Outcome Measures :

1. Clinical significance of CCSVI in MS patients [ Time Frame: 1 month ]
   This will be assessed clinically using annualized relapse rates, Expanded Disability Status Scale (EDSS) change and change in the timed 25 foot walk.
2. Superiority of angioplasty to observation for treatment of CCSVI [ Time Frame: 1 month ]
   This will be assessed clinically using annualized relapse rates, EDSS change, and change in the timed 25-foot walk
3. Incidence of CCSVI in patients with MS [ Time Frame: 0 Months ]
   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.
4. Safety of endovascular treatment of CCSVI [ Time Frame: 1 month ]
   This is defined as the number and nature of any procedure-related adverse effects
5. Target vessel primary and secondary patency [ Time Frame: 1 month ]
   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. Clinical significance of CCSVI in MS patients [ Time Frame: 6 months ]
   This will be assessed clinically using annualized relapse rates, EDSS change and change in the timed 25 foot walk.
7. Clinical significance of CCSVI in MS patients [ Time Frame: 12 months ]
   This will be assessed clinically using annualized relapse rates, EDSS change and change in the timed 25 foot walk.
8. Clinical significance of CCSVI in MS patients [ Time Frame: 18 months ]
   This will be assessed clinically using annualized relapse rates, EDSS change and change in the timed 25 foot walk.
9. Clinical significance of CCSVI in MS patients [ Time Frame: 24 months ]
   This will be assessed clinically using annualized relapse rates, EDSS change and change in the timed 25 foot walk.
10. Superiority of angioplasty to observation for treatment of CCSVI [ Time Frame: 6 Months ]
    This will be assessed clinically using annualized relapse rates, EDSS change, and change in the timed 25-foot walk
11. Superiority of angioplasty to observation for treatment of CCSVI [ Time Frame: 12 Months ]
    This will be assessed clinically using annualized relapse rates, EDSS change, and change in the timed 25-foot walk
12. Superiority of angioplasty to observation for treatment of CCSVI [ Time Frame: 18 Months ]
    This will be assessed clinically using annualized relapse rates, EDSS change, and change in the timed 25-foot walk
13. Superiority of angioplasty to observation for treatment of CCSVI [ Time Frame: 24 Months ]
    This will be assessed clinically using annualized relapse rates, EDSS change, and change in the timed 25-foot walk
14. Safety of endovascular treatment of CCSVI [ Time Frame: 3 months ]
    This is defined as the number and nature of any procedure-related adverse effects
15. Safety of endovascular treatment of CCSVI [ Time Frame: 6 months ]
    This is defined as the number and nature of any procedure-related adverse effects
16. Safety of endovascular treatment of CCSVI [ Time Frame: 12 months ]
    This is defined as the number and nature of any procedure-related adverse effects
17. Safety of endovascular treatment of CCSVI [ Time Frame: 18 months ]
    This is defined as the number and nature of any procedure-related adverse effects
18. Safety of endovascular treatment of CCSVI [ Time Frame: 24 months ]
    This is defined as the number and nature of any procedure-related adverse effects
19. Target vessel primary and secondary patency [ Time Frame: 3 months ]
    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
20. Target vessel primary and secondary patency [ Time Frame: 6 months ]
    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
21. Target vessel primary and secondary patency [ Time Frame: 12 months ]
    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
22. Target vessel primary and secondary patency [ Time Frame: 18 months ]
    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
23. Target vessel primary and secondary patency [ Time Frame: 24 months ]
    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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, New York

Albany Medical Center

Albany, New York, United States, 12208

Image Care Latham

Latham, New York, United States, 12110

Sponsors and Collaborators

Community Care Physicians, P.C.

Investigators

• Principal Investigator: Gary Siskin, MD; Albany Medical College

More Information

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, 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.

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.

• Responsible Party: Gary Siskin, MD, Professor and Chairman, Department of Radiology, Albany Medical College
• ClinicalTrials.gov Identifier: NCT01201707
• Other Study ID Numbers: 2794
• First Posted: September 15, 2010
• Last Update Posted: November 26, 2013
• Last Verified: November 2013

Keywords provided by Gary Siskin, MD, Albany Medical College:

Multiple Sclerosis; Angioplasty; Vein

Additional relevant MeSH terms:

Multiple Sclerosis; Venous Insufficiency; Sclerosis; 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