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Trial registered on ANZCTR


Registration number
ACTRN12619000157178
Ethics application status
Approved
Date submitted
22/10/2018
Date registered
4/02/2019
Date last updated
4/02/2019
Date data sharing statement initially provided
4/02/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Botulinum toxin injections for upper limb tremor
Scientific title
A randomized, double-blind crossover controlled study of botulinum toxin treatment in upper limb tremor
Secondary ID [1] 296358 0
None
Universal Trial Number (UTN)
U1111-1222-4869
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tremor 310085 0
Upper limb proximal dystonic tremor 310086 0
Parkinson's disease tremor 310320 0
lesional tremor 310321 0
Condition category
Condition code
Neurological 308834 308834 0 0
Parkinson's disease
Neurological 309906 309906 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be selected on the basis of upper limb tremor at the shoulder and/or elbow joint either during action, determined by finger-to-nose task and/or posturing with arms outstretch or in the targeting-nose position.

Patients will be randomly assigned to 2 groups, A and B.

The group A will receive BoNTA injection as their first treatment and after a period of 4 months they will be given placebo.
The group B will receive placebo as their first treatment and after a period of 4 months they will be given BoNTA injection.
All injections are intramuscular and performed under needle EMG guidance.

Onabotulinum toxin A (Merz Pharma GmbH & Co. KGaA) will be used for treatment. Each vial of Xeomin, which contains 100 unit of onabotulinum toxin A will be diluted into 2 mL (5U per 0.1mL) using 0.9% sterile saline.

0.9% sterile saline will be used as placebo. All preparations will be prepared by an unmasked person so that patients can be injected in the same intended volume.

The injection dosage will be determined by a blinded, movement disorder specialist according to clinician judgement based on muscles involved according to the pattern of tremor, amplitude of tremor, and action and size of the muscle being injected.

Injections will be performed by a movement disorder specialist experienced in both the assessment of tremor and botulinum toxin injection therapy.

Data collection, clinical assessment and outcomes:
1. Demographic data will be collected, which includes patient’s age, gender, underlying medical condition, tremor onset age, tremor duration.

2. Patients will be required to present themselves for initial assessment and at 4, 8, 12, 16, 20, 24, 28 and 32 weeks for the followings:
• Video recording: A standardized tremor assessment using Fahn, Tolosa, Martin Tremor Rating Scale will be videotaped, renumbered, shuffled and rated by a trained rater. The tremor characteristic will also be recorded, e.g. shoulder abduction/adduction, internal/external rotation, elbow flexion/extension, supination and pronation.
• Patient-specific goal achievement: the Canadian occupational performance or the goal attainment scaling.
• Functional outcome and quality of life: patient-reported Bain and Findley Tremor ADL Scale and Quality of Life in Essential Tremor Questionnaire.
• Muscle strength: Muscles including teres major, teres minor, infraspinatus, supraspinatus, deltoid, pectoralis major, biceps, triceps, finger flexors and extensors will be checked, using the ratings of the Medical Research Council ranging from no contraction of the muscle detectable (0) to full or normal strength (5).
3. Global rating scale:
Global rating for the overall treatment effect, will be obtained at 12 weeks and 24 weeks, by subtracting complication score from peak effect (Peak effect (0-4): 0, no effect; 4, marked reduction in severity and improvement in function; Complication score (0-2): 0, no therapeutic complications; 1, mild complications; 2, severe and disabling complications). The outcome of the treatment was considered to be positive when global rating is equal to or more than 2.
4. Tremor study:
Accelerometry and surface EMG will be used to measure tremor frequency and amplitude. Electrodes will be placed on the four most tremulous muscles of each upper limb (same muscles bilaterally). The electrode placement will be photographed for the reference for follow up study to insure the exact same electrode position in the follow up studies. A standardized protocol including upper limbs at rest, outstretched, at nose-targeting position and when doing finger-nose task will be used. Repeat study will be performed at every month after each injection.

Safety Measures: Patients will be asked to report all the side effects within 24 hours of symptoms onset. Every side effects or complications will be recorded and addressed whenever necessary.
Intervention code [1] 312690 0
Treatment: Drugs
Comparator / control treatment
Every patient will serve as its own comparator group given the crossover design of the study
Control group
Active

Outcomes
Primary outcome [1] 307806 0
Goal Attainment Rating Scale
Timepoint [1] 307806 0
4, 8, 12. 16, 20, 24, 28 and 32 weeks after the Baseline visit. The primary timepoint will be either week 4 or 8 (4-8 weeks post-injection 1), or week 20 or 24 (4-8 weeks post-injection 2), whichever shows the greater improvement in GAS
Secondary outcome [1] 352993 0
1. Canadian Occupational Performance score
Timepoint [1] 352993 0
4, 8, 12. 16, 20, 24, 28 and 32 weeks after the Baseline visit.
Secondary outcome [2] 365569 0
2. Bain and Findley Tremor ADL Scale total score
Timepoint [2] 365569 0
4, 8, 12. 16, 20, 24, 28 and 32 weeks after the Baseline visit.
Secondary outcome [3] 365570 0
3. Quality of Life in Essential Tremor Questionnaire (QUEST scoring)
Timepoint [3] 365570 0
4, 8, 12. 16, 20, 24, 28 and 32 weeks after the Baseline visit.
Secondary outcome [4] 365571 0
4. Fahn, Tolosa, Martin Tremor Rating Scale

Timepoint [4] 365571 0
4, 8, 12. 16, 20, 24, 28 and 32 weeks after the Baseline visit.
Secondary outcome [5] 365572 0
5. The Essential Tremor Rating Assessment Scale
Timepoint [5] 365572 0
4, 8, 12. 16, 20, 24, 28 and 32 weeks after the Baseline visit.
Secondary outcome [6] 365573 0
6 Global rating scale
Timepoint [6] 365573 0
4, 8, 12. 16, 20, 24, 28 and 32 weeks after the Baseline visit.
Secondary outcome [7] 365574 0
7 Amplitude of the accelerometry and surface EMG
Timepoint [7] 365574 0
4, 8, 12. 16, 20, 24, 28 and 32 weeks after the Baseline visit.

Eligibility
Key inclusion criteria
Patients will be selected on the basis of upper limb tremor at the shoulder and/or elbow joint either during action, determined by finger-to-nose task and/or posturing with arms outstretch or in the targeting-nose position.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient treated with BoNTA within 6 months before evaluation
2. Changes in any medications that might affect the severity of tremor within 3 months before enrolling or during the 6 months of evaluation.
3. Inability to comply with the study requirements and follow-up period.
4. Patients with cognitive impairment who is unable to complete the assessment
5. Patients in whom consent is unable to be obtained from themselves or next of kin.

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)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Patients will be randomly assigned to 2 groups, A and B.
The design is the 2-sequence, 2-period, 2-treatment crossover design, with sequences AB and BA
The group A will receive BoNTA injection as their first treatment and after a period of 4 months they will be given placebo.

The group B will receive placebo injection as their first treatment and after period of 4 months they will be given BoNTA injection.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
18/07/2017
Date of last participant enrolment
Anticipated
31/12/2019
Actual
Date of last data collection
Anticipated
28/09/2020
Actual
Sample size
Target
20
Accrual to date
12
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 12194 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 24365 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 300960 0
Hospital
Name [1] 300960 0
Westmead Hospital
Country [1] 300960 0
Australia
Primary sponsor type
Government body
Name
health western sydney local health district
Address
Institute Road
Westmead NSW 2145
PO Box 574
Wentworthville NSW 2145
Country
Australia
Secondary sponsor category [1] 300537 0
Commercial sector/Industry
Name [1] 300537 0
Merz Pharma GmbH & Co. KGa
Address [1] 300537 0
3/244 Coward St, Mascot NSW 2020
Country [1] 300537 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301725 0
Western Sydney Local Health District Human Research and Ethics
Ethics committee address [1] 301725 0
Ethics committee country [1] 301725 0
Australia
Date submitted for ethics approval [1] 301725 0
15/10/2014
Approval date [1] 301725 0
17/03/2017
Ethics approval number [1] 301725 0
HERC/14/WEAD/412

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 3175 3175 0 0
/AnzctrAttachments/376210-PICF-version5-date-MAR 2017-clean.pdf (Participant information/consent)
Attachments [2] 3185 3185 0 0
/AnzctrAttachments/376210-Ethics approval letter.pdf (Ethics approval)
Attachments [3] 3186 3186 0 0
/AnzctrAttachments/376210-Study-Protocol.docx Mar 17.docx clean.docx (Protocol)

Contacts
Principal investigator
Name 87898 0
A/Prof Victor Fung
Address 87898 0
Level 1, Bock A/B, Neurology Department
Westmead Hospital
Cnr Hawkesbury Road and Darcy Road
Westmead NSW 2145
Country 87898 0
Australia
Phone 87898 0
+61 02 96356684
Fax 87898 0
+61 02 96356684
Email 87898 0
vscfung@ozemail.com.au
Contact person for public queries
Name 87899 0
Victor Fung
Address 87899 0
Level 1, Bock A/B, Neurology Department
Westmead Hospital
Cnr Hawkesbury Road and Darcy Road
Westmead NSW 2145
Country 87899 0
Australia
Phone 87899 0
+61 02 96356684
Fax 87899 0
+61 02 96356684
Email 87899 0
vscfung@ozemail.com.au
Contact person for scientific queries
Name 87900 0
Victor Fung
Address 87900 0
Level 1, Bock A/B, Neurology Department
Westmead Hospital
Cnr Hawkesbury Road and Darcy Road
Westmead NSW 2145
Country 87900 0
Australia
Phone 87900 0
+61 02 96356684
Fax 87900 0
+61 02 96356684
Email 87900 0
vscfung@ozemail.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
de-identified individual participant data underlying published results
When will data be available (start and end dates)?
Following publication, no end date
Available to whom?
only researchers who provide a methodologically sound proposal
Available for what types of analyses?
To be decided on case by case basis, decision based on methodologically sound proposal
How or where can data be obtained?
Date will be provided via online access provisional on data access agreement


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.