Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612001173886
Ethics application status
Approved
Date submitted
18/10/2012
Date registered
6/11/2012
Date last updated
6/11/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Repetitive Transcranial Magnetic Stimulation in the treatment of Huntington’s Chorea
Scientific title
For patients with Huntington’s Disease, can repetitive Transcranial Magnetic Stimulation (rTMS) in comparison with sham rTMS, reduce choreic movements.
Secondary ID [1] 281348 0
Nil
Universal Trial Number (UTN)
U1111-1135-5250
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Huntington's disease 287572 0
Condition category
Condition code
Neurological 287897 287897 0 0
Neurodegenerative diseases
Human Genetics and Inherited Disorders 288110 288110 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Repetitive Transcranial Magnetic Stimulation (rTMS).
Both active treatments are applied to the presumed site of motor cortex origin of the hand muscles, regardless of the actual chorea. A total of 900 pulses are delivered at 1Hz (15 minutes). Intensity is set at 100% of magnetic threshold. A MagStim Rapid magnetic stimulator (Magstim, Whitland, UK), connected with a figure-of-eight coil with a diameter of 70mm, will be used to deliver stimuli with the coil handle pointing posteriorly and 45degrees below the coronal plane.
Prior to the commencement of the treatment course, resting motor threshold is measured with single-pulse TMS applied to the motor cortex. The resting motor threshold was measured as the minimal stimulator intensity producing a visible peripheral motor evoked potential response by inspection.
Session by session comparison wherein the stimulus is varied daily (common in rTMS with chorea research), over 10 days (2 week). Washout between active and sham TMS is overnight, or over a weekend if a week based change.
Intervention code [1] 285810 0
Treatment: Devices
Comparator / control treatment
Placebo rTMS.
Placebo rTMS will be conducted using active stimuli applied with the coil rotated at 90degrees to the skull. The technician administering the rTMS thus cannot be blind, but the assessment of movement is conducted by a third party without stimulus knowledge. The participant cannot know which stimulus is intended to be a placebo. It is possible to distinguish the two treatments, but not to identify the sham, so the participant is practically blinded.
Sham rTMS can be performed using the same stimulator connected to the placebo butterfly coil (MCF-P-B-65), which has no stimulating effect on the cortex but produces auditory and tactile sensations similar to those produced by the real coil. Unfortunately we currently do not have this form of coil.
Control group
Placebo

Outcomes
Primary outcome [1] 288109 0
Reduction in choreic movements. The UHDRS chorea severity scale.
Timepoint [1] 288109 0
Before and after each rTMS session.
Primary outcome [2] 288110 0
Global Huntington's severity. General measures for each patient will be made with the Unified Huntington's Disease Rating Scale (UHDRS).
Timepoint [2] 288110 0
Baseline and Final (after 2 week periods)
Secondary outcome [1] 299446 0
Cortical excitability will be measured using a varying number of standard techniques depending on the patient's comfort.
The motor evoked potentials (MEP) threshold curves using MEP amplitude at the Abductor Pollicus Brevis muscle, short-interval cortical inhibition (SICI), long-interval cortical inhibition (LICI), interacortical facilitation and inhibition (IFI), intercortical facilitation and inhibition (IHI, IHF), and silent period have all been used as measures of excitability, but impose varying demands on the patient.
Timepoint [1] 299446 0
Before and after each rTMS session.

Eligibility
Key inclusion criteria
Patients who attended that Huntington’s Study Group (HSG) at the Neurosciences Unit, Graylands Hospital, who have choreic movements, and for whom the movements are especially intrusive or poorly controlled, will be offered the option of the rTMS trial.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Children.
Pregnancy.
History of epilepsy.
Metal implants in the head.
Pacemaker

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 Trial is initially an un-randomised study, but ultimately with a randomised controlled component, and is labelled as such.
A randomised list is generated (SPSS) with the two arms (real rTMS, sham rTMS) and stored separate to the investigation (site manager). Each participant recruited (Consent signed) is assigned an initial arm for the investigation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer package (SPSS for Windows11.5) randomly selected from 200 cases. Participants assigned in sequence of recruitment.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
This study seeks to investigate short term effects (up to 24 hours) on chorea, as have been reported previously, but also will seek to establish a lasting effect of rTMS. In designing these investigations, the value of the scientific information has been balanced against the patient impost, and the likelihood of patient attrition. The project develops in three parts contingent upon a patient’s capacity and interest, with data in each part informing subsequent components.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 286171 0
Government body
Name [1] 286171 0
North Metropolitan Area Health Service
Country [1] 286171 0
Australia
Primary sponsor type
Government body
Name
North Metropolitan Area Health Service
Address
Statewide Department of Neurophysiology
Gascoyne House, Graylands Hospital
John XXIII Avenue
Mount Claremont, Western Australia, 6010.
Country
Australia
Secondary sponsor category [1] 284982 0
Hospital
Name [1] 284982 0
Neuroscience Unit, Graylands Hospital.
Address [1] 284982 0
Ord House, Graylands Hospital
John XXIII Avenue
Mount Claremont, Western Australia, 6010.
Country [1] 284982 0
Australia
Other collaborator category [1] 277133 0
Charities/Societies/Foundations
Name [1] 277133 0
Australian Neuromuscular Research Institute
Address [1] 277133 0
Australian Neuromuscular Research Institute
QEII Medical Centre
Verdun Street
Nedlands, WA, 6009
Country [1] 277133 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288238 0
North Metropolitan Area Mental Health Services Human Research Ethics Committee (EC00273)
Ethics committee address [1] 288238 0
Gascoyne House, Graylands Hospital,
John XXIII Avenue
Mount Claremont WA 6010
Australia
Ethics committee country [1] 288238 0
Australia
Date submitted for ethics approval [1] 288238 0
14/09/2012
Approval date [1] 288238 0
03/10/2012
Ethics approval number [1] 288238 0

Summary
Brief summary
Huntington’s disease (HD) is an autosomal dominant neurodegenerative illness characterized by disorders of movement, cognition, behavior, and functional capacity. In Huntington's disease (HD), the cerebral cortex is involved early in the disease process, and this region has been shown to have abnormal excitability characteristics prior to illness onset, as well as different long term potentiation.
Repetitive Transcranial Magnetic Stimulation (rTMS) is a potential new treatment for depression, and other psychiatric disorders. Using TMS, circuits of the human motor cortex can be activated non-invasively, and because the excitability of neural circuits in the cerebral cortex is not static, repetitive TMS (rTMS) can produce changes in neurotransmission that outlast the period of stimulation. rTMS has been shown to modify excitability in the motor cortex in general, has been used extensively in the treatment of movements in Parkinson’s and other dyskinesias, and has positive preliminary findings in the treatment of Huntington’s chorea.
The purpose of the study is twofold: to investigate the short term effects (up to 24 hours) of inhibitory rTMS on choreic movements as have been reported previously; and to seek to establish a lasting effect of rTMS in a double blind, randomized, sham-controlled study. Firstly, we intend to replicate previous work, using the standard protocol for decreasing excitability in the motor cortex (1Hz). This is also the “best practice” protocol in limited previous studies in this area. The hypothesis, based on previous findings, is that a group receiving rTMS treatment will experience a reduction in choreic movement rating scores when compared with their pre-treatment scores. In addition, the study will extend investigation by applying a complete treatment set of 6 sessions of real treatment, putatively sufficient to induce long term potentiation effects. If such effect is shown, then a sham crossover trial will be continued to compare real and sham effects. The hypothesis is that real rTMS stimulation will be more effective in its long term effect, than the sham form.
The Statewide Department of Neurophysiology has experience in using rTMS in the treatment of depression. In addition, Dr Lee with the Huntington’s Study Group (HSG) at the Neurosciences Unit, Graylands Hospital has extensive experience with this patient population. Patients who attended that unit, who have choreic movements, and for whom the movements are especially intrusive or poorly controlled, will be offered the option of the rTMS trial. This is the rationale for an investigation that combines both fields in an assessment of rTMS as a treatment of choreic movements with Huntington’s disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34793 0
Address 34793 0
Country 34793 0
Phone 34793 0
Fax 34793 0
Email 34793 0
Contact person for public queries
Name 18040 0
Dr Greg Price
Address 18040 0
Statewide Department of Neurophysiology
Gascoyne House, Graylands Hospital,
John XXIII Avenue
Mount Claremont WA 6010
Australia
Country 18040 0
Australia
Phone 18040 0
+61 8 9347 6493
Fax 18040 0
+61 8 9384 5128
Email 18040 0
[email protected]
Contact person for scientific queries
Name 8968 0
Dr Joseph Lee
Address 8968 0
The Statewide Department of Neurophysiology
Graylands Hospital
Brockway Road
Mount Claremont WA 6010
Country 8968 0
Australia
Phone 8968 0
+61 8 9347 6801
Fax 8968 0
+61 8 9384 5128
Email 8968 0
[email protected]

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