Kinematic-based BoNT-A Bilateral Upper Limb PD Therapy

Study Overview
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Brief Summary
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The primary objective is to study the efficacy of botulinum toxin type A (BoNT-A) injected via kinematic parameters in the treatment of unilateral/bilateral upper extremity tremor in Parkinson's disease (PD) tremor. Kinematic assessment tools already developed in past clinical studies will be used in determining injection parameters. The objective is to study the composition of PD tremor using kinematic tools which may contribute to the knowledge of tremor complexity and contribute information that would benefit the development of injection parameters to improve efficacy and optimization of BoNT-A in tremor management. By injecting all bothersome tremulous upper limbs in Parkinson's disease patients, the investigators believe a greater improvement in Quality of Life on more daily tasks can be achieved compared to the investigator's earlier study in unilateral injections (REB#101749), which already showed significant improvement.

Official Title
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Kinematic Characterization of Upper Limb Parkinson's Disease Tremor for Optimized Botulinum Toxin Type A Therapy

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Botulinum Toxin Type A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PD individuals diagnosed by UK Brain Bank Criteria with stage H&Y2-3 disease PD participants who are naïve to PD medications will be grouped into the De novo PD group PD participants stable on a low dose of Levodopa or on their PD medications for at least 3 months prior to their study enrolment will be grouped into the L-dopa PD group Participants who are botulinum toxin naïve for tremor management Patients will be screened for pregnancy by the physician Individuals with PD will be eligible for the study only if tremor is their primary and most bothersome symptom as determined by clinical exam and patient report denoting tremor-dominant phenotype Participants must be able to provide informed consent and to complete all study assessment scales and tasks. Exclusion Criteria: History of stroke History of ALS or Myasthenia Gravis History of COPD or emphysema Underlying arm muscle weakness or any related compartmental muscle syndrome Offending medications (Lithium, valproate, steroids, amiodarone, beta-adrenergic agonists (e.g. salbutamol). Persons prescribed zonisamide History of allergic or side effect reaction to botulinum toxin Contraindications per the BoNT-A drug monograph Women reporting that they are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: De-novo PD<br>A serotype of botulinum toxin type A (BoNT-A) that has specificity for cleavage of SYNAPTOSOMAL-ASSOCIATED PROTEIN 25 (SNAP-25). BoNT-A's pharmacological action is to inhibit the release of acetylcholine from the neuromuscular junction. BoNT-A peripherally applied using optimal parameters by intramuscular injections solely determined by biomechanical analysis of tremulous movements for tremor therapy in both upper extremity every 12 weeks over 42 weeks. BoNT-A dose will range from 50-300 U per arm | Drug: Botulinum Toxin Type A<br> <br> * Other names: BoNT-A;|
| Experimental: L-dopa PD<br>A serotype of botulinum toxin type A (BoNT-A) that has specificity for cleavage of SYNAPTOSOMAL-ASSOCIATED PROTEIN 25 (SNAP-25). BoNT-A's pharmacological action is to inhibit the release of acetylcholine from the neuromuscular junction. BoNT-A peripherally applied using optimal parameters by intramuscular injections solely determined by biomechanical analysis of tremulous movements for tremor therapy in both upper extremity every 12 weeks over 42 weeks. BoNT-A dose will range from 50-300 U per arm | Drug: Botulinum Toxin Type A<br> <br> * Other names: BoNT-A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinematic tremor severity | Change from pre to post-BoNT-A treatments in maximum angular tremor amplitude at the wrist in each treated arm. Angular tremor amplitude is one parameter reflecting the vectoral intensity of tremor segmented at each arm joint | 42 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical tremor severity | Improvement in upper limb tremor severity as determined by an increase >8 points on a standardized clinical assessment tool (Fahn-Tolosa-Marin Tremor Assessment Scale) pre and post BoNT-A injection using kinematic-determined injection parameters in both ET upper limbs | 42 weeks | 
| Accelerometric kinematic tremor severity | Change from pre and post-BoNT-A treatments in maximum log-transformed accelerometric tremor amplitude at wrist level (injected limb). Log-transformed accelerometric tremor amplitude is one parameter reflecting the non-vectoral intensity of tremor. | 42 weeks | 
| Quality of life measures | Quality of life for essential tremor questionnaire is used to measure the patient's impression of change due to treatment and its change on their quality of life. | 42 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Movement disorders, Botulinum toxin type A, Tremor, Kinematics