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

Primary Purpose

Tremor

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
BoNT-A
Sponsored by
Western University, Canada
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Tremor focused on measuring Kinematics, Botulinum toxin type A

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    ET BoNT-A treatment

    PD tremor BoNT-A treatment

    Arm Description

    ET participants treated with kinematic-guided BoNT-A injections over 6 injection cycles

    PD participants treated with kinematic-guided BoNT-A injections over 6 injection cycles

    Outcomes

    Primary Outcome Measures

    Clinical Tremor Rating Scale (Fahn-Tolosa-Marin Tremor Rating Scale)
    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

    Kinematic Tremor Severity
    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

    Full Information

    First Posted
    April 22, 2015
    Last Updated
    August 11, 2019
    Sponsor
    Western University, Canada
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02427646
    Brief Title
    Kinematic-guided BoNT-A Treatment for ET and PD Tremor
    Official Title
    Use of Kinematic Assessment of Hand Tremor Pre- and Post- Treatment With Botulinum Toxin Type A in Essential Tremor and Parkinson Disease
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2019
    Overall Recruitment Status
    Unknown status
    Study Start Date
    October 2011 (Actual)
    Primary Completion Date
    April 2015 (Actual)
    Study Completion Date
    June 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Western University, Canada

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.
    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

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Tremor
    Keywords
    Kinematics, Botulinum toxin type A

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    54 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    ET BoNT-A treatment
    Arm Type
    Experimental
    Arm Description
    ET participants treated with kinematic-guided BoNT-A injections over 6 injection cycles
    Arm Title
    PD tremor BoNT-A treatment
    Arm Type
    Experimental
    Arm Description
    PD participants treated with kinematic-guided BoNT-A injections over 6 injection cycles
    Intervention Type
    Drug
    Intervention Name(s)
    BoNT-A
    Other Intervention Name(s)
    Botulinum neurotoxin type A, IncobotulinumtoxinA
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Clinical Tremor Rating Scale (Fahn-Tolosa-Marin Tremor Rating Scale)
    Description
    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.
    Time Frame
    0 to 96 weeks
    Secondary Outcome Measure Information:
    Title
    Kinematic Tremor Severity
    Description
    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
    Time Frame
    96 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Mandar Jog, MD, FRCPC
    Organizational Affiliation
    Clinical Neurological Sciences
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
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    1579114
    Citation
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    20567945
    Citation
    Evidente VG, Adler CH. An update on the neurologic applications of botulinum toxins. Curr Neurol Neurosci Rep. 2010 Sep;10(5):338-44. doi: 10.1007/s11910-010-0129-z.
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    PubMed Identifier
    17117170
    Citation
    Benito-Leon J, Louis ED. Essential tremor: emerging views of a common disorder. Nat Clin Pract Neurol. 2006 Dec;2(12):666-78; quiz 2p following 691. doi: 10.1038/ncpneuro0347.
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    PubMed Identifier
    7936237
    Citation
    Pullman SL, Elibol B, Fahn S. Modulation of parkinsonian tremor by radial nerve palsy. Neurology. 1994 Oct;44(10):1861-4. doi: 10.1212/wnl.44.10.1861.
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    PubMed Identifier
    8723140
    Citation
    Jankovic J, Schwartz K, Clemence W, Aswad A, Mordaunt J. A randomized, double-blind, placebo-controlled study to evaluate botulinum toxin type A in essential hand tremor. Mov Disord. 1996 May;11(3):250-6. doi: 10.1002/mds.870110306.
    Results Reference
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    PubMed Identifier
    11402109
    Citation
    Brin MF, Lyons KE, Doucette J, Adler CH, Caviness JN, Comella CL, Dubinsky RM, Friedman JH, Manyam BV, Matsumoto JY, Pullman SL, Rajput AH, Sethi KD, Tanner C, Koller WC. A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor. Neurology. 2001 Jun 12;56(11):1523-8. doi: 10.1212/wnl.56.11.1523.
    Results Reference
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    PubMed Identifier
    9380055
    Citation
    Wissel J, Masuhr F, Schelosky L, Ebersbach G, Poewe W. Quantitative assessment of botulinum toxin treatment in 43 patients with head tremor. Mov Disord. 1997 Sep;12(5):722-6. doi: 10.1002/mds.870120516.
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    PubMed Identifier
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    Citation
    Trosch RM, Pullman SL. Botulinum toxin A injections for the treatment of hand tremors. Mov Disord. 1994 Nov;9(6):601-9. doi: 10.1002/mds.870090604.
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    PubMed Identifier
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    Citation
    Samotus O, Rahimi F, Lee J, Jog M. Functional Ability Improved in Essential Tremor by IncobotulinumtoxinA Injections Using Kinematically Determined Biomechanical Patterns - A New Future. PLoS One. 2016 Apr 21;11(4):e0153739. doi: 10.1371/journal.pone.0153739. eCollection 2016.
    Results Reference
    derived

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

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