Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000275066
Ethics application status
Approved
Date submitted
29/03/2010
Date registered
6/04/2010
Date last updated
16/07/2010
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of Botulinum toxin and Repetitive Transcranial Magnetic Stimulation in treating Cervical Dystonia: A Double-blind Placebo Controlled Trial
Scientific title
Among patients with cervical dystonia, does treating with transcranial magnetic stimulation in addition to botulinum toxin treatment compared with botulinum toxin alone, give additional benefit and improve quality of life
Secondary ID [1] 1566 0
nil
Universal Trial Number (UTN)
U1111-1114-5640
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cervical Dystonia 257049 0
Condition category
Condition code
Neurological 257212 257212 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
repetitive Transcranial Magnetic Stimulation (rTMS) given in addition to botulinum toxin treatment given in accordance with clinical need. We will use repetitive Transcranial Magnetic Stimulation (rTMS) parameters demonstrated to have a clinical benefit in a previous case study in cervical dystonia. This will consist of stimulation over the premotor cortex contra lateral to the overactive sternoceidomastoid muscle, 2.5cm anterior to the optimal scalp position for activation of 1st dorsal interosseous muscle. 1200 pulses will be given at a frequency of 1 Hz with an intensity of 90% of motor threshold in a total of 5 consecutive daily sessions, each lasting about 30 minutes. The washout period between the two treatments of the study will be 4 months, after which the participants will receive the alternate treatment.
Intervention code [1] 256225 0
Treatment: Other
Intervention code [2] 256245 0
Treatment: Drugs
Comparator / control treatment
Sham repetitive Transcranial Magnetic Stimulation (rTMS) given in addition to botulinum toxin treatment. Sham treatment will be using the same equipment and parameters as above (a total of 5 consecutive daily sessions, each lasting about 30 minutes before a break of 4 months and then receiving the intervention treatment) but with a 'spacer device' used so that no actual electrical stimulation of cortex by the TMS will be possible. The patients in both groups will continue to have usual treatment with botulinum toxin in accordance with clinical need.
Control group
Placebo

Outcomes
Primary outcome [1] 258102 0
Improvement in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores.
Timepoint [1] 258102 0
At baseline, immediately after repetitive transcranial magnetic stimulation treatment and at 1 and 4 months after treatment
Primary outcome [2] 258131 0
Quality of life measures as measured by the The Short Form (36) Health Survey (SF-36)
Timepoint [2] 258131 0
At baseline, immediately after repetitive transcranial magnetic stimulation treatment and at 1 and 4 months after treatment
Secondary outcome [1] 263707 0
nil
Timepoint [1] 263707 0
nil

Eligibility
Key inclusion criteria
Patients are to be recruited from the Botulinum Toxin Outpatient Clinics at the Monash Medical Centre. All consenting patients with clinical diagnosis of rotational cervical dystonia and stable requirements of Botulinum toxin in the previous 6 months will be included
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria will include those patients with intracranial metal objects or pacemakers, seizures or family history of seizures, pregnant women, those with known excessive alcohol use or serious medical conditions

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)
The patients interested in taking part in the project will be given written information regarding the project. If they provide informed consent to be included in the trial, they will be randomly assigned to treatment with botulinum toxin plus sham rTMS (treatment A) or treatment with botulinum toxin and rTMS (treatment B) according to a computerised random allocation schedule. The clinicians assessing the primary end points will be blinded to which treatment arm the patient is in.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised random allocation schedule
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
29/04/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 256726 0
Hospital
Name [1] 256726 0
Monash Medical Centre
Country [1] 256726 0
Australia
Primary sponsor type
Hospital
Name
Monash Medical Centre
Address
146 Clayton Road
Clayton
Victoria 3168
Country
Australia
Secondary sponsor category [1] 256010 0
None
Name [1] 256010 0
Address [1] 256010 0
Country [1] 256010 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258763 0
Southern Health Ethics Committee
Ethics committee address [1] 258763 0
146 Clayton Road
Clayton Vic 3168
Ethics committee country [1] 258763 0
Australia
Date submitted for ethics approval [1] 258763 0
31/03/2010
Approval date [1] 258763 0
Ethics approval number [1] 258763 0

Summary
Brief summary
Cervical dystonia is the term used to describe a certain pattern of involuntary neck muscle movements. The most effective current treatment for cervical dystonia is injecting overactive muscles with botulinum toxin type A, inducing paralysis of the overactive muscles. Botulinum toxin type A is approved in Australia to treat cervical dystonia. Disadvantages of this therapy are the discomfort associated with the treatment, its temporary effect and lack of response in some cases.
There is emerging evidence for efficacy of low frequency repetitive transcranial magnetic stimulation (rTMS), for relief of symptoms in focal forms of dystonia, including cervical dystonia. rTMS is a technique for stimulating a part of the brain in a non-invasive way. In this case, magnetic pulses are delivered through the scalp and stimulate the brain cells. The procedure is largely pain free and has no significant adverse effects. This technique has been used for research as well as treatment of several neurological disorders. rTMS can lead to changes in the brain area stimulated, that persist after the stimulus. There is some evidence that these changes can be used in the treatment of cervical dystonia. However, it is still an experimental treatment. This means that it is not an approved treatment for treatment of dystonia in Australia or other parts of the world.

This study aims to investigate if treatment of cervical dystonia with Botulinum toxin injection, when combined with rTMS, produces an additive effect. If the latter treatment is found to have a significant additive effect, it may offer a rationale to directly compare rTMS with botulinum toxin. If rTMS is effective as a treatment on its own, it may offer a less painful and perhaps longer lasting alternative to botulinum toxin injections.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30992 0
Address 30992 0
Country 30992 0
Phone 30992 0
Fax 30992 0
Email 30992 0
Contact person for public queries
Name 14239 0
Dr Ganga Ganesvaran
Address 14239 0
Department of Neurology
146 Clayton Road
Clayton
Victoria 3168
Country 14239 0
Australia
Phone 14239 0
+61 3 95946666
Fax 14239 0
Email 14239 0
[email protected]
Contact person for scientific queries
Name 5167 0
Dr Ganga Ganesvaran
Address 5167 0
Department of Neurology
146 Clayton Road
Clayton
Victoria 3168
Country 5167 0
Australia
Phone 5167 0
+61 3 95946666
Fax 5167 0
Email 5167 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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