Factors Determining the Efficacy of Botulinum Toxin for Arm Tremor in Dystonia

NCT ID: NCT06411028

Last Updated: 2025-03-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-01

Study Completion Date

2027-05-30

Brief Summary

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Tremor occurs in up to 55% of dystonia patients, which is known as dystonic tremor syndrome (DTS). Tremor can be present in the body part affected by dystonia (dystonic tremor, DT), or an unaffected body part (tremor associated with dystonia, TAWD). DTS can be treated with botulinum neurotoxin (BoNT) injections, but BoNT is effective in only about 60-70% of patients. It is unknown which patients benefit most from BoNT treatment. The investigators aim to explore the associations between clinical and pathophysiological tremor characteristics and BoNT efficacy. To do so, the investigatorswill measure clinical, electrophysiological, ultrasonographic and (functional) magnetic resonance imaging ((f)MRI) characteristics before the start of BoNT treatment and measure BoNT efficacy after three three-monthly BoNT sessions.

Detailed Description

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Rationale: Tremor occurs in up to 55% of dystonia patients, which is known as dystonic tremor syndrome (DTS). Tremor can be present in the body part affected by dystonia (dystonic tremor, DT), or an unaffected body part (tremor associated with dystonia, TAWD). DTS can be treated with botulinum neurotoxin (BoNT) injections, but BoNT is effective in only about 60-70% of patients. It is unknown which patients benefit from BoNT treatment. This highlights the need for personalized treatment.

Objective: The primary objective is to explore the associations between clinical, electrophysiological, ultrasonographic and (functional) magnetic resonance imaging ((f)MRI) tremor characteristics and BoNT efficacy in DTS of the upper extremity. The secondary objectives are to:

* Explore the clinical, electrophysiological, ultrasonographic and (f)MRI differences between DT and TAWD of the upper extremity.
* Explore the agreement between a clinical assessment, polymyography (PMG) and muscle ultrasound (MUS) on muscle selection in DTS of the upper extremity.

Study design: An uncontrolled multi-centre low-intervention clinical trial where subjects participate for ± 8 months Study population: 60 adults with DTS (± 30 DT/ 30 TAWD) of the upper extremity who start 12-weekly BoNT treatment in normal clinical practice.

Main study parameters/endpoints: the associations between clinical, electrophysiological, ultrasonographic, and (f)MRI tremor characteristics at baseline and BoNT efficacy (change in TRG Essential Tremor Rating Assessment Scale (TETRAS) from baseline to 28 weeks).

Secondary trial endpoints:

* The clinical, electrophysiological, ultrasonographic and (f)MRI differences between DT and TAWD at baseline.
* The agreement between a clinical assessment, PMG and MUS on muscle selection. Intervention: Participants are treated with three consecutive BoNT sessions in normal clinical practice. Participants will undergo additional diagnostic procedures: 2 clinical assessments, 2 PMGs, 1 MUS recordings and 1 fMRI assessment and will fill in 2 questionnaires before and after the BoNT sessions.

Conditions

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Dystonic Tremor Syndrome

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Uncontrolled multi-centre low-intervention clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Botulinum toxin

Participants are treated with three consecutive BoNT sessions.

Group Type EXPERIMENTAL

Polymyography

Intervention Type DIAGNOSTIC_TEST

We will measure muscle activity using surface electromyography and tremor using inertial measurement units while subjects perform rest, posturing and kinetic tasks.

Muscle ultrasound

Intervention Type DIAGNOSTIC_TEST

We will obtain B-mode images and videos of upper extremity muscles of the most affected upper extremity.

(Functional) magnetic resonance imaging

Intervention Type DIAGNOSTIC_TEST

Subjects will undergo (f)MRI scanning involving concurrent electromyography, accelerometry and functional magnetic resonance imaging.

Clinical assessment

Intervention Type DIAGNOSTIC_TEST

We will assess tremor and dystonia severity using clinical scales.

Questionnaires

Intervention Type DIAGNOSTIC_TEST

We will collect patient-reported outcomes.

botulinum toxin injection (BTX A)

Intervention Type DRUG

Three consequetive botulinum toxin injections of the upper extremities

Interventions

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Polymyography

We will measure muscle activity using surface electromyography and tremor using inertial measurement units while subjects perform rest, posturing and kinetic tasks.

Intervention Type DIAGNOSTIC_TEST

Muscle ultrasound

We will obtain B-mode images and videos of upper extremity muscles of the most affected upper extremity.

Intervention Type DIAGNOSTIC_TEST

(Functional) magnetic resonance imaging

Subjects will undergo (f)MRI scanning involving concurrent electromyography, accelerometry and functional magnetic resonance imaging.

Intervention Type DIAGNOSTIC_TEST

Clinical assessment

We will assess tremor and dystonia severity using clinical scales.

Intervention Type DIAGNOSTIC_TEST

Questionnaires

We will collect patient-reported outcomes.

Intervention Type DIAGNOSTIC_TEST

botulinum toxin injection (BTX A)

Three consequetive botulinum toxin injections of the upper extremities

Intervention Type DRUG

Other Intervention Names

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Tremor registration Poly-electromyography

Eligibility Criteria

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Inclusion Criteria

* Clinical diagnosis of dystonic tremor or tremor associated with dystonia according to the 2018 consensus statement on the classification of tremors
* Tremor of one or both upper extremities
* Starting botulinum toxin injections as part of normal clinical practice
* Age ≥ 18 years

Exclusion Criteria

* Acquired aetiology of dystonic tremor syndrome
* Previous botulinum toxin treatment of the to be treated upper extremity for ≥ 4 consecutive sessions
* In case of previous botulinum toxin treatment of the to be treated upper extremity for ≤3 consecutive sessions: the last botulinum toxin injections ≤ 6 months before study enrolment
* Unstable dose medications for dystonia and tremor ≤ 1 month before study enrolment
* Deep brain stimulation implantation ≤ 6 months before study enrolment
* Unstable deep brain stimulation variables ≤ 1 month before study enrolment
* Comorbidity interfering with study participation
* Known hypersensitivity for components of Dysport
* Infection at the upper extremity
* Pregnancy, trying to conceive and breastfeeding
* Insufficient knowledge of the Dutch or English language


* Contraindications for MRI (e.g. previous brain surgery, claustrophobia, active implant, epilepsy, metal objects in the upper body that are incompatible with MRI)
* Moderate to severe head tremor while lying supine (to avoid artefacts caused by extensive head motion during scanning).
* Inability to provoke postural tremor while lying supine.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Canisius-Wilhelmina Hospital

OTHER

Sponsor Role collaborator

Donders Centre for Cognitive Neuroimaging

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Anke Snijders, PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

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Donders Centre for Cognitive Neuroimaging

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Canisius-Wilhelmina Ziekenhuis

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Iris Visser, MSc

Role: CONTACT

+310243616600

Rick Helmich, PhD

Role: CONTACT

Facility Contacts

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Iris Visser, MSc

Role: primary

+310243610750

Rick Helmich, PhD

Role: backup

+310243610750

Iris Visser, MSc

Role: primary

+310243616600

Anke Snijders, PhD

Role: backup

+310243616600

Iris Visser, MSc

Role: primary

+31243658210

Frouke Nijhuis, MSc

Role: backup

+31243658210

References

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Nieuwhof F, Toni I, Dirkx MF, Gallea C, Vidailhet M, Buijink AWG, van Rootselaar AF, van de Warrenburg BPC, Helmich RC. Cerebello-thalamic activity drives an abnormal motor network into dystonic tremor. Neuroimage Clin. 2022;33:102919. doi: 10.1016/j.nicl.2021.102919. Epub 2021 Dec 16.

Reference Type BACKGROUND
PMID: 34929584 (View on PubMed)

Panyakaew P, Cho HJ, Lee SW, Wu T, Hallett M. The Pathophysiology of Dystonic Tremors and Comparison With Essential Tremor. J Neurosci. 2020 Nov 25;40(48):9317-9326. doi: 10.1523/JNEUROSCI.1181-20.2020. Epub 2020 Oct 23.

Reference Type BACKGROUND
PMID: 33097635 (View on PubMed)

Other Identifiers

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2024-515970-28

Identifier Type: OTHER

Identifier Source: secondary_id

115083

Identifier Type: -

Identifier Source: org_study_id

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