Kinematic-based BoNT-A Injections for Bilateral ET

Botulinum Toxin Type A for Injection of Bilateral Upper Extremity Tremor in Patients With Essential Tremor Using Kinematic Assessment

The primary objective is to study the efficacy of botulinum toxin type A (Xeomin®) injected utilizing kinematically-based injection parameters for the treatment of upper extremity essential tremor (ET). Additional objectives are to study the benefit of kinematic assessment tools in determining injection parameters and to study the composition of tremor using kinematics.

Study Overview

• Status: Unknown
• Conditions: Essential Tremor
• Intervention / Treatment: Drug: Botulinum toxin type A

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A5A5
      • London Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Consenting male and female participants
• Diagnosis of 'definite essential tremor' in accordance with the TRIG criteria including: ET individuals diagnosed with upper limb tremor in their motor dominant and non-dominant hands
• Stable ET medication management for the 3 month duration prior to their enrollment in the study
• Participants who are botulinum toxin naïve for tremor management
• Patients will be screened for pregnancy by the physician

Exclusion Criteria:

• History of stroke
• Muscle weakness or any related compartmental muscle syndrome
• Smoking
• History of ALS or Myasthenia Gravis
• 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 Xeomin® drug monograph
• Women reporting that they are pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Essential tremor treatment; 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. Participants will be treated by BoNT-A injections every 12 weeks over 72 weeks. BoNT-A parameters will be determined solely by biomechanical analysis of tremulous movements in both upper extremity BoNT-A dose will range from 50-300 U per arm

Drug: Botulinum toxin type A; Other Names: Xeomin; IncobotulinumtoxinA; BoNT-A

What is the study measuring?

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	72 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 Xeomin® injection using kinematic-determined injection parameters in both ET upper limbs	72 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.	72 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.	72 weeks

Collaborators and Investigators

• Sponsor: Western University, Canada
• Investigators: Principal Investigator: Mandar Jog, MD, LHSC

Publications and helpful links

General Publications

• Adler CH, Bansberg SF, Hentz JG, Ramig LO, Buder EH, Witt K, Edwards BW, Krein-Jones K, Caviness JN. Botulinum toxin type A for treating voice tremor. Arch Neurol. 2004 Sep;61(9):1416-20. doi: 10.1001/archneur.61.9.1416.
• Zesiewicz TA, Elble R, Louis ED, Hauser RA, Sullivan KL, Dewey RB Jr, Ondo WG, Gronseth GS, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: therapies for essential tremor: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005 Jun 28;64(12):2008-20. doi: 10.1212/01.WNL.0000163769.28552.CD. Epub 2005 Jun 22.
• 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.
• 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.
• 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.
• 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.
• 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.
• Gironell A, Kulisevsky J. Diagnosis and management of essential tremor and dystonic tremor. Ther Adv Neurol Disord. 2009 Jul;2(4):215-22. doi: 10.1177/1756285609104791.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2014
• Primary Completion (Anticipated): September 1, 2020
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: September 11, 2015
• First Submitted That Met QC Criteria: September 14, 2015
• First Posted (Estimate): September 16, 2015

Study Record Updates

• Last Update Posted (Actual): June 22, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Botulinum toxin type A; Kinematics; Movement disorders
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; incobotulinumtoxinA
• Other Study ID Numbers: 104584