ANZCTR - Registration

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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]

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

Condition category

Condition code

Neurological

Neurodegenerative diseases

Human Genetics and Inherited Disorders

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]

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]

Reduction in choreic movements. The UHDRS chorea severity scale.

Timepoint [1]

Before and after each rTMS session.

Primary outcome [2]

Global Huntington's severity. General measures for each patient will be made with the Unified Huntington's Disease Rating Scale (UHDRS).

Timepoint [2]

Baseline and Final (after 2 week periods)

Secondary outcome [1]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

North Metropolitan Area Health Service

Address [1]

Statewide Department of Neurophysiology
Gascoyne House, Graylands Hospital
John XXIII Avenue
Mount Claremont, Western Australia, 6010.

Country [1]

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]

Hospital

Name [1]

Neuroscience Unit, Graylands Hospital.

Address [1]

Ord House, Graylands Hospital
John XXIII Avenue
Mount Claremont, Western Australia, 6010.

Country [1]

Australia

Other collaborator category [1]

Charities/Societies/Foundations

Name [1]

Australian Neuromuscular Research Institute

Address [1]

Australian Neuromuscular Research Institute
QEII Medical Centre
Verdun Street
Nedlands, WA, 6009

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

North Metropolitan Area Mental Health Services Human Research Ethics Committee (EC00273)

Ethics committee address [1]

Gascoyne House, Graylands Hospital,
John XXIII Avenue
Mount Claremont WA 6010
Australia

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

14/09/2012

Approval date [1]

03/10/2012

Ethics approval number [1]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Dr Greg Price

Address

Statewide Department of Neurophysiology
Gascoyne House, Graylands Hospital,
John XXIII Avenue
Mount Claremont WA 6010
Australia

Country

Australia

Phone

+61 8 9347 6493

Fax

+61 8 9384 5128

Greg.Price@health.wa.gov.au

Contact person for scientific queries

Name

Dr Joseph Lee

Address

The Statewide Department of Neurophysiology
Graylands Hospital
Brockway Road
Mount Claremont WA 6010

Country

Australia

Phone

+61 8 9347 6801

Fax

+61 8 9384 5128

Joseph.Lee@health.wa.gov.au

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

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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