Dystonic Tremor SyndromePhase 4BATNCT06411028
Factors Determining the Efficacy of Botulinum Toxin for Arm Tremor in Dystonia
A Phase 4 study testing Polymyography, Muscle ultrasound and (Functional) magnetic resonance imaging in people with Dystonic Tremor Syndrome, run by Radboud University Medical Center at 3 sites in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dystonic Tremor Syndrome
- What is being tested?
- Polymyography, Muscle ultrasound and (Functional) magnetic resonance imaging
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 3 sitesNetherlands
- Study dates
- 1 Jan 2025to 30 Jan 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
Donders Centre for Cognitive Neuroimaging
Nijmegen, Gelderland, 6525 EN
Radboud University Medical Center
Nijmegen, Gelderland, 6525 GA
Canisius-Wilhelmina Ziekenhuis
Nijmegen, Gelderland, 6532 SZ
About this study
Official title: 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.
Read the 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.
- Conditions
- Dystonic Tremor Syndrome
- Being tested
- Polymyography, Muscle ultrasound, (Functional) magnetic resonance imaging, Clinical assessment, Questionnaires
- Keywords
- Botulinum neurotoxin, Botulinum toxin, Dystonia, Dystonic tremor syndrome, Dystonic tremor, Tremor associated with dystonia, Upper extremity, Functional magnetic resonance imaging, fMRI, Muscle ultrasound
- Medical subject headings
- Dystonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PolymyographyDiagnostic test
Also called Tremor registration, Poly-electromyography
We will measure muscle activity using surface electromyography and tremor using inertial measurement units while subjects perform rest, posturing and kinetic tasks.
Muscle ultrasoundDiagnostic test
We will obtain B-mode images and videos of upper extremity muscles of the most affected upper extremity.
(Functional) magnetic resonance imagingDiagnostic test
Subjects will undergo (f)MRI scanning involving concurrent electromyography, accelerometry and functional magnetic resonance imaging.
Clinical assessmentDiagnostic test
We will assess tremor and dystonia severity using clinical scales.
QuestionnairesDiagnostic test
We will collect patient-reported outcomes.
botulinum toxin injection (BTX A)Drug
Three consequetive botulinum toxin injections of the upper extremities
| Study group | Role | What they receive |
|---|---|---|
| Botulinum toxin | Experimental | Participants are treated with three consecutive BoNT sessions. Receives: 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 28 weeks
Secondary outcomes (11)
Tremor severity assessed by the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS)
FTM-TRS [0-152]: higher scores indicate a more severe tremor.
Measured: Baseline, 28 weeks
Dystonia severity assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM-DRS)
BFM-DRS [0-150]: higher scores indicate more severe dystonia.
Measured: Baseline, 28 weeks
Additional neurological signs assessed by the Standardised Tremor Elements Assessment (STEA)
STEA [0-27]: higher scores make a diagnosis of dystonic tremor syndrome instead of essential tremor more likely.
Measured: Baseline
Quality of life assessed by the Quality of Life Essential Tremor Questionnaire (QUEST)
QUEST [0-120]: higher scores indicate greater dissatisfaction.
Measured: Baseline, 28 weeks
Psychological stress assessed by the Perceived stress scale (PSS)
PSS [0-4]: higher scores indicate higher levels of perceived stress
Measured: Baseline, 28 weeks
Pain assessed by the Numeric Pain Rating Scale (NPRS)
NPRS [0-10]: 0 indicates no pain and 10 the worst imaginable pain
Measured: Baseline, 28 weeks
Patient-reported change in tremor severity assessed by the Patient Global Impression of Change (PGIC)
PGIC [-3: much worse, -2: moderately worse, -1: slightly worse, 0: no change, 1: slightly better, 2: moderately better, 3: much better]
Measured: 28 weeks
Electrophysiological characteristics
e.g. tremor power, dominant frequency, frequency-width at half-width power, intermuscular coherence, tremulous muscles
Measured: Baseline, 28 weeks
Ultrasonographic tremulous activity
Measured: Baseline
Tremor related cerebral activity
Quantified using functional MRI scanning
Measured: Baseline
Botulinum toxin parameters
e.g. injection schemes, rationale for muscle selection, adherence
Measured: Baseline, 12 and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2024
- Study start1 Jan 2025
- Primary completion30 Jan 2027 (estimated)
- Study completion30 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Dystonic Tremor SyndromeStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Uncontrolled multi-centre low-intervention clinical trial
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Canisius-Wilhelmina Hospital, Donders Centre for Cognitive Neuroimaging
- Responsible party
- Sponsor
- Investigators
- Anke Snijders, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06411028
- Sponsor's protocol ID
- 115083
- Other IDs
- 2024-515970-28
- Acronym
- BAT
- Status last verified
- Aug 2026
- First submitted
- 8 May 2024
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pseudonymised participant data will be shared in the Radboud Data Repository.
Publications
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.
PubMed 34929584Panyakaew 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.
PubMed 33097635
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Factors Determining the Efficacy of Botulinum Toxin for Arm Tremor in Dystonia: An Exploratory Study
- ClinicalTrials.gov ID
- NCT06411028
- Acronym / sponsor ID
- BAT / 115083
- 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
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Canisius-Wilhelmina Hospital, Donders Centre for Cognitive Neuroimaging
- Study start
- 1 Jan 2025 (actual)
- Primary completion
- 30 Jan 2027 (estimated)
- Study completion
- 30 Jan 2027 (estimated)
- First posted
- 13 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Uncontrolled multi-centre low-intervention clinical trial
| Arm | Type | Receives |
|---|---|---|
| Botulinum toxin | Experimental | 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)Participants are treated with three consecutive BoNT sessions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PolymyographyAlso: Tremor registration, Poly-electromyographyWe will measure muscle activity using surface electromyography and tremor using inertial measurement units while subjects perform rest, posturing and kinetic tasks. | Diagnostic test | Botulinum toxin |
| Muscle ultrasoundWe will obtain B-mode images and videos of upper extremity muscles of the most affected upper extremity. | Diagnostic test | Botulinum toxin |
| (Functional) magnetic resonance imagingSubjects will undergo (f)MRI scanning involving concurrent electromyography, accelerometry and functional magnetic resonance imaging. | Diagnostic test | Botulinum toxin |
| Clinical assessmentWe will assess tremor and dystonia severity using clinical scales. | Diagnostic test | Botulinum toxin |
| QuestionnairesWe will collect patient-reported outcomes. | Diagnostic test | Botulinum toxin |
| botulinum toxin injection (BTX A)Three consequetive botulinum toxin injections of the upper extremities | Drug | Botulinum toxin |
Primary outcome
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.
11 secondary outcomes
Tremor severity assessed by the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS)
Time frame: Baseline, 28 weeks
Dystonia severity assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM-DRS)
Time frame: Baseline, 28 weeks
Additional neurological signs assessed by the Standardised Tremor Elements Assessment (STEA)
Time frame: Baseline
Quality of life assessed by the Quality of Life Essential Tremor Questionnaire (QUEST)
Time frame: Baseline, 28 weeks
Psychological stress assessed by the Perceived stress scale (PSS)
Time frame: Baseline, 28 weeks
Pain assessed by the Numeric Pain Rating Scale (NPRS)
Time frame: Baseline, 28 weeks
Patient-reported change in tremor severity assessed by the Patient Global Impression of Change (PGIC)
Time frame: 28 weeks
Electrophysiological characteristics
Time frame: Baseline, 28 weeks
Ultrasonographic tremulous activity
Time frame: Baseline
Tremor related cerebral activity
Time frame: Baseline
Botulinum toxin parameters
Time frame: Baseline, 12 and 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2026.
- Background: PubMed 34929584Nieuwhof 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.
- Background: PubMed 33097635Panyakaew 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.
- Individual participant dataSharing planned: Yes. Pseudonymised participant data will be shared in the Radboud Data Repository.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anke Snijders, PhD principal investigator
Radboud University Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Polymyography, Muscle ultrasound and (Functional) magnetic resonance imaging in people with Dystonic Tremor Syndrome, run by Radboud University Medical Center at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tremor severity assessed by the TRG Essential Tremor Rating Assessment Scale (TETRAS) (time frame: Baseline, 28 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06411028, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.