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

May 8, 2024 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. We aim to explore the associations between clinical and pathophysiological tremor characteristics and BoNT efficacy. To do so, we will 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

Not yet 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 differences in BoNT efficacy between DT and TAWD of the upper extremity. Secondary objectives are to: explore the electrophysiological and cerebral differences between DT and TAWD of the upper extremity, 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, and explore the agreement between a clinical assessment, polymyography (PMG) and muscle ultrasound (MUS) on muscle selection in DTS of the upper extremity.

Study design: Explorative prospective multi-centre cohort study Study population: 60 adults with DTS (± 30 DT/ 30 TAWD) of the upper extremity who start 12-weekly BoNT treatment as part of standard care.

Main study parameters/endpoints: The primary outcome measure is clinical tremor severity quantified by the TRG Essential Tremor Rating Assessment Scale (TETRAS) at 28 weeks. We will also collect clinical, electrophysiological, ultrasonographic and (f)MRI measures and patient-reported outcomes.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Subjects do not benefit from participation. The risk of the extra study procedures is negligible. The study procedures are harmless, but may be tiring. The time burden consists of five extra hours spent at the hospital divided across three visits and filling in questionnaires (one hour). The baseline visit for MRI scanning and the visit at 28 weeks are extra compared to standard care.

Study Type

Observational

Enrollment (Estimated)

60

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

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

Sampling Method

Non-Probability Sample

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 DT or TAWD according to the 2018 consensus statement on the classification of tremors
  • Tremor of one or both upper extremities
  • Age ≥ 18 years

Exclusion Criteria:

  • Contraindications for BoNT treatment
  • Previous BoNT treatment of upper extremity
  • 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
  • Pregnancy or breastfeeding
  • Insufficient knowledge of the Dutch 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

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
Our primary outcome will be clinical tremor severity measured by the TRG Essential Tremor Rating Assessment Scale (TETRAS) (35) 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
Cognitive functioning assessed by Montreal Cognitive Assessment (MOCA)
Time Frame: Baseline
MOCA [0-30]: score ≥ 26 indicates normal cognitive functioning.
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
Ultrasonographic characteristics
Time Frame: Baseline, 28 weeks
e.g. echogenicity, muscle thickness, tremulous muscles
Baseline, 28 weeks
(f)MRI characteristics
Time Frame: Baseline
e.g. grey matter volume, tremor related-activity in cerebello-thalamo-cortical circuit and basal ganglia
Baseline
Botulinum toxin parameters
Time Frame: Baseline, 12 and 24 weeks
e.g. injection schemes, rationale for muscle selection, adherence
Baseline, 12 and 24 weeks

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 (Estimated)

July 1, 2024

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)

May 13, 2024

Last Update Submitted That Met QC Criteria

May 8, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 115083
  • NL86546.091.24 (Other Identifier: CCMO-Register)

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

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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