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Kinematic-guided BoNT-A Treatment for ET and PD Tremor

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ClinicalTrials.gov Identifier: NCT02427646
Recruitment Status : Active, not recruiting
First Posted : April 28, 2015
Results First Posted : August 20, 2019
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Mandar Jog, Western University, Canada

Brief Summary:
The present study attempts to fill a critical knowledge gap of BoNT A in tremor management by studying the efficacy of IncobotulinumtoxinA (Xeomin®) injection for hand tremor in essential tremor and idiopathic Parkinson disease using data regarding composition of tremor obtained through sophisticated, yet clinically accessible multi-sensor based kinematic information.

Condition or disease Intervention/treatment Phase
Tremor Drug: BoNT-A Phase 2

Detailed Description:
Current pharmacological agents used to treat Parkinson disease (PD) tremor and essential tremor (ET) provide suboptimal benefit and are commonly associated with significant adverse effects. Botulinum toxin type A (BoNT-A) has been shown to be effective for wrist tremor though functionally bothersome muscle weakness frequently occurs. This is the longest study to date demonstrating that BoNT-A therapy coupled with kinematic guidance can provide efficacious outcomes for upper limb tremor with minimized unwanted weakness. A total of 28 PD and 24 ET participants with bothersome, disabling tremor, received six serial BoNT-A treatments every 16 weeks starting at week 0 with a follow-up visit 6 weeks following a treatment, totaling 96 weeks. Clinical scales, including Fahn-Tolosa-Marin tremor rating scale (FTM), and sensor-based tremor assessments were conducted at each visit. Kinematics was utilized to identify which arm muscles contributed to the tremulous movements and the experienced injector used clinical expertise in determining BoNT-A dosages. Following BoNT-A treatment, clinical ratings of tremor severity and functional ability (FTM) showed significant improvements following the first treatment which was maintained up to week 96 in PD and ET. Kinematics detected a significant reduction in PD and ET tremor amplitudes by 70% and 76% over the treatment course, respectively. By objectively distinguishing tremulous muscles and tremor severity, adverse effects were limited to mild perceived weakness by participants in injected muscles during follow-ups. Following the fourth treatment, BoNT-A dosages in flexor and extensor wrist muscles and biceps were reduced for those experiencing residual weakness which ultimately did not interfere with tremor relief or arm function. Kinematics is an objective method that can aid clinicians in assessing and determining optimal BoNT-A parameters to alleviate both PD and ET tremor. BoNT-A injections are tolerable and effective when focal therapy regimens are determined and optimized kinematically over a long-term

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Use of Kinematic Assessment of Hand Tremor Pre- and Post- Treatment With Botulinum Toxin Type A in Essential Tremor and Parkinson Disease
Actual Study Start Date : October 2011
Actual Primary Completion Date : April 2015
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Botox Tremor

Arm Intervention/treatment
Experimental: ET BoNT-A treatment
ET participants treated with kinematic-guided BoNT-A injections over 6 injection cycles
Drug: BoNT-A
A serotype of botulinum toxins 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 to treat tremor in the most bothersome upper extremity every 16 weeks over 96 weeks. The study will be extended for those participants who benefited and will receive treatment every 12 weeks over 96 weeks. BoNT-A dose will range from 50-300 U per arm.
Other Names:
  • Botulinum neurotoxin type A
  • IncobotulinumtoxinA

Experimental: PD tremor BoNT-A treatment
PD participants treated with kinematic-guided BoNT-A injections over 6 injection cycles
Drug: BoNT-A
A serotype of botulinum toxins 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 to treat tremor in the most bothersome upper extremity every 16 weeks over 96 weeks. The study will be extended for those participants who benefited and will receive treatment every 12 weeks over 96 weeks. BoNT-A dose will range from 50-300 U per arm.
Other Names:
  • Botulinum neurotoxin type A
  • IncobotulinumtoxinA




Primary Outcome Measures :
  1. Clinical Tremor Rating Scale (Fahn-Tolosa-Marin Tremor Rating Scale) [ Time Frame: 0 to 96 weeks ]
    Improvement in hand tremor as determined by a reduction of >8 points on a standardized clinical assessment tool (Fahn-Tolosa-Marin Tremor Assessment Scale) pre and post Xeomin® injection using kinematic guided injection parameters for both IPD and ET. Lower scores indicate a better outcome. Means and standard deviations are provided in the data tables. FTM minimum and maximum scores range from 0 to 92 FTM points.


Secondary Outcome Measures :
  1. Kinematic Tremor Severity [ Time Frame: 96 weeks ]
    For two subgroups of participants: (A) those with a > 8 point improvement on the tremor rating scale and (B) those with a change ≤ 8 points on the tremor rating scale, Group A will have 50% reduction in overall tremor amplitude as measured by kinematics. Kinematic measures were graphically represented as mean angular RMS amplitude and standard deviations of the population at the wrist over three trials during scripted task. Kinematic tremor analysis is shown in angular root mean square (RMS) amplitudes



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Consenting male and female participants, aged 18 years to 80 years
  • PD individuals diagnosed by UK Brain Bank Criteria with stage H&Y2-3 disease or ET with hand tremor in their motor dominant hand
  • Stable IPD/ET medication management for the 6 month duration prior to their enrollment in the study
  • Individuals with IPD will be eligible for the study only if tremor is their primary and most bothersome symptom as determined by clinical exam and patient report
  • Participants who are botulinum toxin naïve for tremor management

Exclusion Criteria:

  • History of stroke
  • Muscle weakness or any related compartmental muscle syndrome
  • Smoking
  • Offending medications (Lithium, valproate, steroids, amiodarone, beta-adrenergic agonists (e.g. salbutamol))
  • Contradictions per the Xeomin® drug monograph
  • Patients prescribed zonisamide

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02427646


Sponsors and Collaborators
Western University, Canada
Investigators
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Principal Investigator: Mandar Jog, MD, FRCPC Clinical Neurological Sciences

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Mandar Jog, Neurologist, Director of the London Movement Disorders Centre, Western University, Canada
ClinicalTrials.gov Identifier: NCT02427646     History of Changes
Other Study ID Numbers: 18445
First Posted: April 28, 2015    Key Record Dates
Results First Posted: August 20, 2019
Last Update Posted: August 20, 2019
Last Verified: August 2019
Keywords provided by Mandar Jog, Western University, Canada:
Kinematics
Botulinum toxin type A
Additional relevant MeSH terms:
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Tremor
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Botulinum Toxins
Botulinum Toxins, Type A
abobotulinumtoxinA
incobotulinumtoxinA
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents