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

NCT02427646 | Unknown Phase 2 Results

• 1 other identifier: 18445
• Study Type: interventional
• Target: 54
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Tremor

Keywords

Kinematics; Botulinum toxin type A

Outcome Measures

Primary Outcomes (1)

• 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.

  0 to 96 weeks

Secondary Outcomes (1)

• Kinematic Tremor Severity

  96 weeks

Study Arms (2)

ET BoNT-A treatment

EXPERIMENTAL

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

Drug: BoNT-A

PD tremor BoNT-A treatment

EXPERIMENTAL

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

Drug: BoNT-A

Interventions

BoNT-A DRUG

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.

Also known as: Botulinum neurotoxin type A, IncobotulinumtoxinA

ET BoNT-A treatment; PD tremor BoNT-A treatment

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Western University, Canada: lead

Related Publications (9)

• 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.

  PMID: 1579114 BACKGROUND

• 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.

  PMID: 20567945 BACKGROUND

• 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.

  PMID: 17117170 BACKGROUND

• 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.

  PMID: 7936237 BACKGROUND

• 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.

  PMID: 8723140 BACKGROUND

• 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.

  PMID: 11402109 BACKGROUND

• 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.

  PMID: 9380055 BACKGROUND

• 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.

  PMID: 7845399 BACKGROUND

• 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.

  PMID: 27101283 DERIVED

MeSH Terms

Conditions

Tremor

Interventions

incobotulinumtoxinA; Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Limitations and Caveats

A specialized quality of life relating to tremor in PD participants would be more appropriate due to other symptoms PD patients experience. Blinded studies are not possible as muscle weakness can be easily recognized by patients and investigators

Results Point of Contact

• Title: Dr. Mandar Jog
• Organization: LHSC

mandar.jog@lhsc.on.ca

519-685-8500

Study Officials

• Mandar Jog, MD, FRCPC

  Clinical Neurological Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurologist, Director of the London Movement Disorders Centre

Study Record Dates

• First Submitted: April 22, 2015
• First Posted: April 28, 2015
• Study Start: October 1, 2011
• Primary Completion: April 1, 2015
• Study Completion: June 1, 2020
• Last Updated: August 20, 2019
• Results First Posted: August 20, 2019

Record last verified: 2019-08