ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

U1111-1222-4869

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Tremor

Upper limb proximal dystonic tremor

Parkinson's disease tremor

lesional tremor

Condition category

Condition code

Neurological

Parkinson's disease

Neurological

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]

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]

Goal Attainment Rating Scale

Timepoint [1]

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]

1. Canadian Occupational Performance score

Timepoint [1]