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
About this trial
This is an interventional treatment trial for Tremor focused on measuring Kinematics, Botulinum toxin type A
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
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
NCT ID
NCT02427646
First Posted
April 22, 2015
Last Updated
August 11, 2019
Sponsor
Western University, Canada
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:
PubMed Identifier
1579114
Citation
Schantz EJ, Johnson EA. Properties and use of botulinum toxin and other microbial neurotoxins in medicine. Microbiol Rev. 1992 Mar;56(1):80-99. doi: 10.1128/mr.56.1.80-99.1992.
Results Reference
background
PubMed Identifier
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.
Results Reference
background
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.
Results Reference
background
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.
Results Reference
background
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
background
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
background
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.
Results Reference
background
PubMed Identifier
7845399
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.
Results Reference
background
PubMed Identifier
27101283
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
Learn more about this trial
Kinematic-guided BoNT-A Treatment for ET and PD Tremor
We'll reach out to this number within 24 hrs