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

NCT06411028 | Recruiting Phase 4

• 2 other identifiers: 1150832024-515970-28
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Dystonic Tremor Syndrome

Keywords

Botulinum neurotoxin; Botulinum toxin; Dystonia; Dystonic tremor syndrome; Dystonic tremor; Tremor associated with dystonia; Upper extremity; Functional magnetic resonance imaging; fMRI; Muscle ultrasound

Outcome Measures

Primary Outcomes (1)

• Tremor severity assessed by the TRG Essential Tremor Rating Assessment Scale (TETRAS)

  The primary outcome is the clinical tremor severity measured by the TRG Essential Tremor Rating Assessment Scale (TETRAS) at 28 weeks. The scale ranges between 0 and 112 points, with higher scores indicating a more severe tremor. The TETRAS consists of two subcategories: a 12-item activities of daily living subscale and a 9-item performance scale. The daily living subscale is scored by interviewing the participant. The performance scale is rated by observing the participants while they are performing multiple tasks.

  Baseline, 28 weeks

Secondary Outcomes (11)

• Tremor severity assessed by the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS)

  Baseline, 28 weeks

• Dystonia severity assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM-DRS)

  Baseline, 28 weeks

• Additional neurological signs assessed by the Standardised Tremor Elements Assessment (STEA)

  Baseline

• Quality of life assessed by the Quality of Life Essential Tremor Questionnaire (QUEST)

  Baseline, 28 weeks

• Psychological stress assessed by the Perceived stress scale (PSS)

  Baseline, 28 weeks

Study Arms (1)

Botulinum toxin

EXPERIMENTAL

Participants are treated with three consecutive BoNT sessions.

Diagnostic Test: Polymyography; Diagnostic Test: Muscle ultrasound; Diagnostic Test: (Functional) magnetic resonance imaging; Diagnostic Test: Clinical assessment; Diagnostic Test: Questionnaires; Drug: botulinum toxin injection (BTX A)

Interventions

Polymyography DIAGNOSTIC_TEST

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

Also known as: Tremor registration, Poly-electromyography

Botulinum toxin

Muscle ultrasound DIAGNOSTIC_TEST

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

Botulinum toxin

(Functional) magnetic resonance imaging DIAGNOSTIC_TEST

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

Botulinum toxin

Clinical assessment DIAGNOSTIC_TEST

We will assess tremor and dystonia severity using clinical scales.

Botulinum toxin

Questionnaires DIAGNOSTIC_TEST

We will collect patient-reported outcomes.

Botulinum toxin

botulinum toxin injection (BTX A) DRUG

Three consequetive botulinum toxin injections of the upper extremities

Botulinum toxin

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Canisius-Wilhelmina Hospital: collaborator
• Donders Centre for Cognitive Neuroimaging: collaborator

Study Sites (3)

Donders Centre for Cognitive Neuroimaging

Nijmegen, Gelderland, 6525 EN, Netherlands

RECRUITING

Radboud University Medical Center

Nijmegen, Gelderland, 6525 GA, Netherlands

RECRUITING

Canisius-Wilhelmina Ziekenhuis

Nijmegen, Gelderland, 6532 SZ, Netherlands

RECRUITING

Related Publications (2)

• 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.

  PMID: 34929584 BACKGROUND

• 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.

  PMID: 33097635 BACKGROUND

MeSH Terms

Conditions

Dystonia

Interventions

Magnetic Resonance Imaging; Botulinum Toxins

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; 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

• Anke Snijders, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Iris Visser, MSc

CONTACT

+310243616600; iris.visser@radboudumc.nl

Rick Helmich, PhD

CONTACT

rick.helmich@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Uncontrolled multi-centre low-intervention clinical trial

Study Record Dates

• First Submitted: May 8, 2024
• First Posted: May 13, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 30, 2027
• Last Updated: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data will be published after publishing summary data.
• Access Criteria: Data will be shared upon reasonable request after signing a data transfer agreement.

Locations

NL (3)