Trial registered on ANZCTR


Trial ID
ACTRN12612000302853
Ethics application status
Approved
Date submitted
9/03/2012
Date registered
16/03/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised, blinded, controlled study of percutaneous transluminal angioplasty (PTA) for extracranial vein stenoses in patients with multiple sclerosis (MS)
Scientific title
In multiple sclerosis patients with extracranial and/or azygos vein stenosis, is percutaneous balloon angioplasty more effective than a sham procedure in terms of changes to physical, neurological and cognitive function?
Secondary ID [1] 279953 0
Nil known
Universal Trial Number (UTN)
Trial acronym
MS PTA study

Health condition
Health condition(s) or problem(s) studied:
Extracranial and/or azygous vein stenoses in patients with Multiple Sclerosis 285868 0
Condition category
Condition code
Neurological 286053 286053 0 0
Multiple sclerosis
Cardiovascular 286229 286229 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Percutaneous Transluminal Angioplasty (PTA) is a minimally invasive procedure done under sedation and with image guidance using x-rays called angiography. It takes about an hour and a half to two hours. A fine wire called a catheter containing a small inflatable balloon is moved through the veins to the point of narrowing. At that point the balloon is inflated stretching and opening the vein. The catheter and balloon are then pulled back and removed from the veins. Participants will be randomised to the treatment group, angiography + PTA,or to the control group who will have the angiogram without the ballooning. The participants and neurologists will not know who has had the treatment. At 12 months all participants will have another angiogram. The participants that were originally inthe control group will have the ballooning at 12 months. The participants and neurologists will not know at which time point the ballooning was performed.
Intervention code [1] 284284 0
Treatment: surgery
Comparator / control treatment
PTA procedure compared to the control group. The control group will get a sham PTA procedure (the angiogram without the ballooning) at the beginning of the study. The control group will cross over to the treatment arm at 12 months. The study will be double blinded (the neurologist and the patients will not know at which time point, 0 or 12 months, the PTA procedure was performed.
Control group
Placebo

Outcomes
Primary outcome [1] 286534 0
Change in clinical parameters and disease progression as measured by Kurtzke Extended Disability Status Scale (EDSS)
Timepoint [1] 286534 0
One week; one, three, six and twelve months compared to baseline
Primary outcome [2] 286669 0
Change in clinical parameters and disease progression as measured by the Multiple Sclerosis Functional Composite Score (MSFC).
Timepoint [2] 286669 0
One week; one, three, six and twelve months compared to baseline
Primary outcome [3] 286670 0
Change in clinical parameters and disease progression as measured by Cognitive Assessment Tool (CogState).
Timepoint [3] 286670 0
One week; one, three, six and twelve months compared to baseline
Secondary outcome [1] 296104 0
1. Composite number of procedural and post procedural adverse events (to 12 months) measured Common Terminology Criteria for Adverse Events v 4 (CTCAE),
Timepoint [1] 296104 0
One week; one, three, six and twelve months compared to baseline
Secondary outcome [2] 296419 0
Restoration of venous outflow (to 75% from normal outflow) as measured by venogram, US and MRV at six and 12 months.
Timepoint [2] 296419 0
Six and twelve months compared to baseline
Secondary outcome [3] 296420 0
Change in patient reported quality of life measured by the Multiple Sclerosis Quality of Life-54 Instrument (MSQoL-54)
Timepoint [3] 296420 0
One week; one, three, six and twelve months compared to baseline
Secondary outcome [4] 296421 0
Change in patient reported fatigue as measured by the Fatigue Severity Scale (FSS)
Timepoint [4] 296421 0
One week; one, three, six and twelve months compared to baseline

Eligibility
Key inclusion criteria
*Signed Participant Information and Consent Form;
*Age 18 to 65 years;
*Expanded Disability Disease Scale Score (EDSS) ranging from 0 to 7.5;
*Diagnosis of MS according to the revised McDonald criteria;
*Therapy with currently approved disease-modifying treatments;
*Normal renal function or pre-hydration;
*No allergy to contrast media or pre-treatment;
*Abnormal extracranial vein venogram:
1. Stenosis at any level
2. Abnormal filling of vertebral veins following a jugular bulb injection
3. Delayed emptying of the internal jugular vein in the supine position
4. Persistent filling of the internal jugular vein in the erect position
5. Abnormal appearance of the internal jugular valve
6. Stenosis of the thoracic azygos vein
7. Delayed emptying of the thoracic azygos vein.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*pregnancy or planning a pregnancy within the next two years
*Relapse, disease progression, and steroid treatment in the 30 days preceding study entry (all conditions significantly modify clinical parameters, rendering unreliable any postoperative assessment);
*Pre-existing medical conditions known to be associated with brain pathology, including neurodegenerative disorder, cerebrovascular disease, and history of alcohol abuse; *Abnormal renal function with a calculated e-GFR <60 and pre-hydration not possible;
*Allergy to contrast and pre-treatment not possible; *Refusal to undergo the endovascular treatment or randomisation.
*Previous PTA on extracranial veins
*Unable to adequately perform the CogState cognitive assessment tool because of visual or manual dexterity impairment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Potential participants will have a consultation with the study radiologist and have the procedure and risks described. They will be given a copy of the the Participants Information and Consent Form and the research coordinators' contact number. Potential participants will be asked to take time to consider their voluntary participation in the study. They will be told that if they decide to participate they will need to contact the research coordinators for an appointment. The coordinators will question the potential participants about their understanding of the study, ask if they have any concerns or further questions prior to obtaining consent. If further consultation is required with the radiologist for explanation of the procedure this will be organised. If consent is obtained the potiential participants will then have their screening and baseline imaging and their neurological and cognitive assessment with the study neurologist to determine eligibility to participate. When eligibility is confirmed the procedure (angiogram +/- PTA) date will be scheduled. The radiologist will be given the allocated randomisation for each participant at the start of the angiogram procedure . The participants and neurologists will be blinded, that is they will not know at which time point, at start of the study or at 12 months, the PTA procedure was performed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The Alfred biostatistician will be asked to generate a randomisation list. Participants will be randomised to an angiogram plus the PTA or to just the angiogram without the PTA. Dark brown envelopes with sequential numbers one to 180 will be perpared. The envelopes will contain the randomisation allocation as per the list generated by the biostatistician. The envelopes will be stored in a locked cupboard; they will be given to the radiologist sequentially at the start of the angiography procedure.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
The participants in the control group, that is the group that get the angiogram without the PTA at the start of the study, will cross over to the PTA trreatment arm at 12 months. All participants and the neurologists will not know whether the PTA was performed at the start of the study or at 12 months.
Phase
Not Applicable
Type of endpoint(s)
Efficacy

Recruitment
Anticipated date of first participant enrolment
1/04/2012
Actual date of first participant enrolment
Anticipated date last participant enrolled
Actual date last participant enrolled
Anticipated date of last data collection
Actual date of last data collection
Target sample size
160
Actual sample size
Recruitment status
Completed
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 284722 0
Other
Name [1] 284722 0
The Alfred Radiology Research Fund
Address [1] 284722 0
Radiology Department
The Alfred
55 Commercial Road
Melbourne, Vic 3004
Country [1] 284722 0
Australia
Primary sponsor type
Other
Name
The Alfred Hospital
Address
The Alfred
55 Commercial Road
Melbourne, Vic 3004
Country
Australia
Secondary sponsor category [1] 283732 0
None
Name [1] 283732 0
Address [1] 283732 0
Country [1] 283732 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286726 0
The Alfred Human Research Ethics Committee
Ethics committee address [1] 286726 0
Ground Floor
Commercial Road
Melbourne, Victoria, 3004
Ethics committee country [1] 286726 0
Australia
Date submitted for ethics approval [1] 286726 0
15/05/2011
Approval date [1] 286726 0
06/02/2012
Ethics approval number [1] 286726 0
1/11/0120

Summary
Brief summary
To assess the safety and effectiveness of percutaneous transluminal angioplasty (PTA) for the treatment of extracranial and/or azygous vein stenosis in MS patients as measured by clinical parameters of physical and mental disability progression.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 33785 0
Address 33785 0
Country 33785 0
Phone 33785 0
Fax 33785 0
Email 33785 0
Contact person for public queries
Name 17032 0
Helen Kavnoudias
Address 17032 0
Radiology Research Unit
RAdiology Department
The Alfred
Level 1 Phillip Block
55 Commercial Road
Melbourne, Vic, 3004
Country 17032 0
Australia
Phone 17032 0
+61 3 9076 3606
Fax 17032 0
+61 3 9076 2153
Email 17032 0
h.kavnoudias@alfred.org.au
Contact person for scientific queries
Name 7960 0
Helen Kavnoudias
Address 7960 0
Radiology Research Unit
RAdiology Department
The Alfred
Level 1 Phillip Block
55 Commercial Road
Melbourne, Vic, 3004
Country 7960 0
Australia
Phone 7960 0
+61 3 9076 3606
Fax 7960 0
+61 3 9076 2153
Email 7960 0
h.kavnoudias@alfred.org.au