Factors Determining the Efficacy of Botulinum Toxin for Arm Tremor in Dystonia
- Conditions
- Dystonic Tremor Syndrome
- Interventions
- Diagnostic Test: PolymyographyDiagnostic Test: Muscle ultrasoundDiagnostic Test: (Functional) magnetic resonance imagingDiagnostic Test: Clinical assessmentDiagnostic Test: QuestionnairesDrug: botulinum toxin injection (BTX A)
- Registration Number
- NCT06411028
- Lead Sponsor
- Radboud University Medical Center
- 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Botulinum toxin Polymyography Participants are treated with three consecutive BoNT sessions. Botulinum toxin Muscle ultrasound Participants are treated with three consecutive BoNT sessions. Botulinum toxin (Functional) magnetic resonance imaging Participants are treated with three consecutive BoNT sessions. Botulinum toxin Clinical assessment Participants are treated with three consecutive BoNT sessions. Botulinum toxin Questionnaires Participants are treated with three consecutive BoNT sessions. Botulinum toxin botulinum toxin injection (BTX A) Participants are treated with three consecutive BoNT sessions.
- Primary Outcome Measures
Name Time Method Tremor severity assessed by the TRG Essential Tremor Rating Assessment Scale (TETRAS) 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.
- Secondary Outcome Measures
Name Time Method Tremor severity assessed by the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) Baseline, 28 weeks FTM-TRS \[0-152\]: higher scores indicate a more severe tremor.
Dystonia severity assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM-DRS) Baseline, 28 weeks BFM-DRS \[0-150\]: higher scores indicate more severe dystonia.
Additional neurological signs assessed by the Standardised Tremor Elements Assessment (STEA) Baseline STEA \[0-27\]: higher scores make a diagnosis of dystonic tremor syndrome instead of essential tremor more likely.
Quality of life assessed by the Quality of Life Essential Tremor Questionnaire (QUEST) Baseline, 28 weeks QUEST \[0-120\]: higher scores indicate greater dissatisfaction.
Psychological stress assessed by the Perceived stress scale (PSS) Baseline, 28 weeks PSS \[0-4\]: higher scores indicate higher levels of perceived stress
Pain assessed by the Numeric Pain Rating Scale (NPRS) Baseline, 28 weeks NPRS \[0-10\]: 0 indicates no pain and 10 the worst imaginable pain
Patient-reported change in tremor severity assessed by the Patient Global Impression of Change (PGIC) 28 weeks PGIC \[-3: much worse, -2: moderately worse, -1: slightly worse, 0: no change, 1: slightly better, 2: moderately better, 3: much better\]
Electrophysiological characteristics Baseline, 28 weeks e.g. tremor power, dominant frequency, frequency-width at half-width power, intermuscular coherence, tremulous muscles
Ultrasonographic tremulous activity Baseline Tremor related cerebral activity Baseline Quantified using functional MRI scanning
Botulinum toxin parameters Baseline, 12 and 24 weeks e.g. injection schemes, rationale for muscle selection, adherence
Trial Locations
- Locations (3)
Donders Centre for Cognitive Neuroimaging
🇳🇱Nijmegen, Gelderland, Netherlands
Radboud University Medical Center
🇳🇱Nijmegen, Gelderland, Netherlands
Canisius-Wilhelmina Ziekenhuis
🇳🇱Nijmegen, Gelderland, Netherlands