Kinematic-based BoNT-A Bilateral Upper Limb PD Therapy

NCT02668497 | Unknown Phase 2

• 1 other identifier: 107433
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to study the efficacy of botulinum toxin type A (BoNT-A) injected via kinematic parameters in the treatment of unilateral/bilateral upper extremity tremor in Parkinson's disease (PD) tremor. Kinematic assessment tools already developed in past clinical studies will be used in determining injection parameters. The objective is to study the composition of PD tremor using kinematic tools which may contribute to the knowledge of tremor complexity and contribute information that would benefit the development of injection parameters to improve efficacy and optimization of BoNT-A in tremor management. By injecting all bothersome tremulous upper limbs in Parkinson's disease patients, the investigators believe a greater improvement in Quality of Life on more daily tasks can be achieved compared to the investigator's earlier study in unilateral injections (REB#101749), which already showed significant improvement.

Conditions

Parkinson's Disease

Keywords

Movement disorders; Botulinum toxin type A; Tremor; Kinematics

Outcome Measures

Primary Outcomes (1)

• 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

  42 weeks

Secondary Outcomes (3)

• Clinical tremor severity

  42 weeks

• Accelerometric kinematic tremor severity

  42 weeks

• Quality of life measures

  42 weeks

Study Arms (2)

De-novo PD

EXPERIMENTAL

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. BoNT-A peripherally applied using optimal parameters by intramuscular injections solely determined by biomechanical analysis of tremulous movements for tremor therapy in both upper extremity every 12 weeks over 42 weeks. BoNT-A dose will range from 50-300 U per arm

Drug: Botulinum Toxin Type A

L-dopa PD

EXPERIMENTAL

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. BoNT-A peripherally applied using optimal parameters by intramuscular injections solely determined by biomechanical analysis of tremulous movements for tremor therapy in both upper extremity every 12 weeks over 42 weeks. BoNT-A dose will range from 50-300 U per arm

Drug: Botulinum Toxin Type A

Interventions

Botulinum Toxin Type A DRUG

Also known as: IncobotulinumtoxinA, BoNT-A

De-novo PD; L-dopa PD

Eligibility Criteria

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

You may qualify if:

• PD individuals diagnosed by UK Brain Bank Criteria with stage H\&Y2-3 disease
• PD participants who are naïve to PD medications will be grouped into the "De novo" PD group
• PD participants stable on a low dose of Levodopa or on their PD medications for at least 3 months prior to their study enrolment will be grouped into the "L-dopa" PD group
• Participants who are botulinum toxin naïve for tremor management
• Patients will be screened for pregnancy by the physician
• Individuals with PD will be eligible for the study only if tremor is their primary and most bothersome symptom as determined by clinical exam and patient report denoting tremor-dominant phenotype
• Participants must be able to provide informed consent and to complete all study assessment scales and tasks.

You may not qualify if:

• History of stroke
• History of ALS or Myasthenia Gravis
• History of COPD or emphysema
• Underlying arm muscle weakness or any related compartmental muscle syndrome
• 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 BoNT-A drug monograph
• Women reporting that they are pregnant

Sponsors & Collaborators

• Western University, Canada: lead

Study Sites (1)

London Health Sciences Centre

London, Ontario, N6A5A5, Canada

Location

Related Publications (8)

• Milanov I. A cross-over clinical and electromyographic assessment of treatment for parkinsonian tremor. Parkinsonism Relat Disord. 2001 Sep;8(1):67-73. doi: 10.1016/s1353-8020(00)00077-8.

  PMID: 11472883 BACKGROUND

• Kraus PH, Lemke MR, Reichmann H. Kinetic tremor in Parkinson's disease--an underrated symptom. J Neural Transm (Vienna). 2006 Jul;113(7):845-53. doi: 10.1007/s00702-005-0354-9. Epub 2006 Jan 30.

  PMID: 16804646 BACKGROUND

• Jimenez MC, Vingerhoets FJ. Tremor revisited: treatment of PD tremor. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S93-5. doi: 10.1016/S1353-8020(11)70030-X.

  PMID: 22166467 BACKGROUND

• Imbach LL, Sommerauer M, Leuenberger K, Schreglmann SR, Maier O, Uhl M, Gassert R, Baumann CR. Dopamine-responsive pattern in tremor patients. Parkinsonism Relat Disord. 2014 Nov;20(11):1283-6. doi: 10.1016/j.parkreldis.2014.09.007. Epub 2014 Sep 16.

  PMID: 25260965 BACKGROUND

• Miyasaki JM, Martin W, Suchowersky O, Weiner WJ, Lang AE. Practice parameter: initiation of treatment for Parkinson's disease: an evidence-based review [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2002 Jan 8;58(1):11-7. doi: 10.1212/wnl.58.1.11.

  PMID: 11781398 BACKGROUND

• Nagatsua T, Sawadab M. L-dopa therapy for Parkinson's disease: past, present, and future. Parkinsonism Relat Disord. 2009 Jan;15 Suppl 1:S3-8. doi: 10.1016/S1353-8020(09)70004-5.

  PMID: 19131039 BACKGROUND

• Stathis P, Konitsiotis S, Antonini A. Dopamine agonists early monotherapy for the delay of development of levodopa-induced dyskinesias. Expert Rev Neurother. 2015 Feb;15(2):207-13. doi: 10.1586/14737175.2015.1001747. Epub 2015 Jan 12.

  PMID: 25578445 BACKGROUND

• Katzenschlager R, Sampaio C, Costa J, Lees A. Anticholinergics for symptomatic management of Parkinson's disease. Cochrane Database Syst Rev. 2003;2002(2):CD003735. doi: 10.1002/14651858.CD003735.

  PMID: 12804486 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Movement Disorders; Tremor

Interventions

Botulinum Toxins, Type A; incobotulinumtoxinA

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Neurologic Manifestations; 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

Study Officials

• Mandar Jog, MD

  LHSC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 26, 2016
• First Posted: January 29, 2016
• Study Start: March 1, 2016
• Primary Completion: August 1, 2020
• Study Completion: December 1, 2020
• Last Updated: March 11, 2020

Record last verified: 2020-03

Locations

CA (1)