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

March 19, 2025 updated by: Radboud University Medical Center

Factors Determining the Efficacy of Botulinum Toxin for Arm Tremor in Dystonia: an Exploratory Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525 GA
        • Recruiting
        • Radboud University Medical Center
        • Contact:
        • Contact:
          • Iris Visser, MSc
        • Contact:
        • Contact:
          • Anke Snijders, PhD
      • Nijmegen, Gelderland, Netherlands, 6532 SZ
        • Recruiting
        • Canisius-Wilhelmina Ziekenhuis
        • Contact:
        • Contact:
        • Contact:
          • Frouke Nijhuis, MSc
      • Nijmegen, Gelderland, Netherlands, 6525 EN
        • Recruiting
        • Donders Centre for Cognitive Neuroimaging
        • Contact:
        • Contact:
        • Contact:
          • Rick Helmich, PhD
        • Contact:
          • Iris Visser, MSc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Study Population

We will include 60 patients with DTS who start 12-weekly BoNT treatment as part of regular care. We aim for a balanced distribution (± 30/30) between DT and TAWD. Patients will be recruited from the outpatient clinics of Radboudumc and the CWZ hospital.

Description

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

Exclusion criteria for MRI scanning:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Botulinum toxin
Participants are treated with three consecutive BoNT sessions.
Diagnostic test: Polymyography
We will measure muscle activity using surface electromyography and tremor using inertial measurement units while subjects perform rest, posturing and kinetic tasks.
Other Names:
  • Tremor registration
  • Poly-electromyography
Diagnostic test: Muscle ultrasound
We will obtain B-mode images and videos of upper extremity muscles of the most affected upper extremity.
Diagnostic test: (Functional) magnetic resonance imaging
Subjects will undergo (f)MRI scanning involving concurrent electromyography, accelerometry and functional magnetic resonance imaging.
Diagnostic test: Clinical assessment
We will assess tremor and dystonia severity using clinical scales.
Diagnostic test: Questionnaires
We will collect patient-reported outcomes.
Drug: botulinum toxin injection (BTX A)
Three consequetive botulinum toxin injections of the upper extremities

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tremor severity assessed by the TRG Essential Tremor Rating Assessment Scale (TETRAS)
Time Frame: Baseline, 28 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tremor severity assessed by the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS)
Time Frame: Baseline, 28 weeks
FTM-TRS [0-152]: higher scores indicate a more severe tremor.
Baseline, 28 weeks
Dystonia severity assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM-DRS)
Time Frame: Baseline, 28 weeks
BFM-DRS [0-150]: higher scores indicate more severe dystonia.
Baseline, 28 weeks
Additional neurological signs assessed by the Standardised Tremor Elements Assessment (STEA)
Time Frame: Baseline
STEA [0-27]: higher scores make a diagnosis of dystonic tremor syndrome instead of essential tremor more likely.
Baseline
Quality of life assessed by the Quality of Life Essential Tremor Questionnaire (QUEST)
Time Frame: Baseline, 28 weeks
QUEST [0-120]: higher scores indicate greater dissatisfaction.
Baseline, 28 weeks
Psychological stress assessed by the Perceived stress scale (PSS)
Time Frame: Baseline, 28 weeks
PSS [0-4]: higher scores indicate higher levels of perceived stress
Baseline, 28 weeks
Pain assessed by the Numeric Pain Rating Scale (NPRS)
Time Frame: Baseline, 28 weeks
NPRS [0-10]: 0 indicates no pain and 10 the worst imaginable pain
Baseline, 28 weeks
Patient-reported change in tremor severity assessed by the Patient Global Impression of Change (PGIC)
Time Frame: 28 weeks
PGIC [-3: much worse, -2: moderately worse, -1: slightly worse, 0: no change, 1: slightly better, 2: moderately better, 3: much better]
28 weeks
Electrophysiological characteristics
Time Frame: Baseline, 28 weeks
e.g. tremor power, dominant frequency, frequency-width at half-width power, intermuscular coherence, tremulous muscles
Baseline, 28 weeks
Botulinum toxin parameters
Time Frame: Baseline, 12 and 24 weeks
e.g. injection schemes, rationale for muscle selection, adherence
Baseline, 12 and 24 weeks
Ultrasonographic tremulous activity
Time Frame: Baseline
Baseline
Tremor related cerebral activity
Time Frame: Baseline
Quantified using functional MRI scanning
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

Canisius-Wilhelmina Hospital
Donders Centre for Cognitive Neuroimaging

Investigators

  • Principal Investigator: Anke Snijders, PhD, Radboud University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2025

Primary Completion (Estimated)

May 30, 2027

Study Completion (Estimated)

May 30, 2027

Study Registration Dates

First Submitted

May 8, 2024

First Submitted That Met QC Criteria

May 8, 2024

First Posted (Actual)

May 13, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 19, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 115083
  • 2024-515970-28 (Other Identifier: Clinical Trials Information System (CTIS))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Pseudonymised participant data will be shared in the Radboud Data Repository.

IPD Sharing Time Frame

Data will be published after publishing summary data.

IPD Sharing Access Criteria

Data will be shared upon reasonable request after signing a data transfer agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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