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

NCT ID: NCT02427646

Last Updated: 2019-08-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2020-06-30

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

Conditions

Tremor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ET BoNT-A treatment

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

Group Type: EXPERIMENTAL

BoNT-A

Intervention Type: 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.

PD tremor BoNT-A treatment

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

Group Type: EXPERIMENTAL

BoNT-A

Intervention Type: 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.

Interventions

BoNT-A

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.

Intervention Type: DRUG

Other Intervention Names

Botulinum neurotoxin type A; IncobotulinumtoxinA

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Western University, Canada

OTHER

Sponsor Role: lead

Responsible Party

Mandar Jog

Neurologist, Director of the London Movement Disorders Centre

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mandar Jog, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Clinical Neurological Sciences

References

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.

Reference Type: BACKGROUND

PMID: 1579114 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20567945 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17117170 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7936237 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 8723140 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11402109 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9380055 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7845399 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27101283 (View on PubMed)

Other Identifiers

18445

Identifier Type: -

Identifier Source: org_study_id