Clinical trial NCT04650958: SUNDYS: A Multicenter, Randomized, Double-blind, Sham-controlled, Parallel-group Trial
Official title: Subthalamic Nucleus Deep Brain Stimulation in Isolated Generalized or Segmental Dystonia: A Multicenter, Randomized, Double-blind, Sham-controlled, Parallel-group Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Dystonia
Keywords: Deep brain stimulation
Subthalamic nucleus
Randomized controlled trial
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Renmin Hospital of Wuhan University
name: Shanghai Tongji Hospital, Tongji University School of Medicine
name: Second Affiliated Hospital of Soochow University
name: West China Hospital
First posted: 2020-12-03
Enrollment: 38
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In this study after having DBS leads implanted successfully, 38 patients will be randomly assigned to either the control or experimental group with a 1:1 allocation. The experimental group will receive continuous DBS stimulation for 3 months, while controls will have sham stimulation for 3 months.
Primary purpose: TREATMENT

Brief summary: Dystonia is a group of movement disorders characterized by twisting, repetitive movements, or abnormal postures caused by involuntary muscle contractions and is characterized by a young age of onset and a high disability rate. Early intervention can reduce disability incidence, improve the patient's quality of life, and reduce the burden on families and society. Multiple international guidelines on dystonia have found deep brain stimulation (DBS) to be a safe and effective treatment for refractory dystonia. The globus pallidal internus (GPi) is the mostly widely used target for dystonia. However, there are limitations on the GPi DBS treatment, including slow onset of beneficial effects, poor improvement of axis symptoms, and potential stimulation-related side effects. Previous studies have described the highly successful use of subthalamic nucleus deep brain stimulation (STN DBS) in patients with refractory dystonia, suggesting that STN DBS is an effective and persisting alternative to pallidal deep brain stimulation. However, all STN DBS treated cases have been analyzed in open-label uncontrolled cohort studies, leading to limited data with a high level of evidence on the STN DBS in dystonia. Further, the investigators hypothesized STN has potentially more effectiveness when compared with GPi, and may be more power-saving and quick-acting. In this study, the investigators will organize a prospective randomized, double-blind, parallel-group, multicenter study comparing active versus sham stimulation in isolated segmental or generalized dystonia to evaluate the effectiveness and safety of STN DBS by measuring the impact on motor status, mental status, quality of life, the rate of response of the patients (the number of patients with ≥30% improvement in the movement score on the Burke-Fahn-Marsden Dystonia Rating Scale) and the rate of adverse events during the trial.


Eligibility criteria: Inclusion Criteria:

1. Patients must meet criteria for the diagnosis of isolated generalized or segmental dystonia, including idiopathic and inherited dystonia, as defined by the Phenomenology and Classification of Dystonia: A Consensus Update 2013;
2. Patients will be ≥ 14 years old;
3. The course of disease will be ≥ 3 years;
4. Patients will have:

   1. Significant dystonia symptoms;
   2. Compromised life quality;
   3. Unsatisfactory response to oral treatment with anticholinergic agents antiepileptic agents, anti-dopamine agents, dopaminergic agents, or muscle relaxants;
   4. Unsatisfactory response to or contraindication for previous botulinum toxin treatment; and
   5. Ability to provide written informed consent.

Exclusion Criteria:

1. Patients with a diagnosis or probable diagnosis of acquired, compound, and complex dystonia, as defined by the Phenomenology and Classification of Dystonia: A Consensus Update 2013;
2. Previous brain surgery for dystonia;
3. Patients with cognitive impairment (MMSE score \<24) or moderate-severe depressive disorder (BDI\>25);
4. Patients with marked brain atrophy identified by magnetic resonance imaging (MRI) or computed tomography (CT);
5. Patients with other medical or psychiatric comorbidities that could increase the surgical risk or interfere with completion of the trial;
6. Patients with increased bleeding risk, or other factors contraindicating neurosurgery or general anesthesia;
7. Patients unable to cooperate with the assessments during the follow-up.

Primary outcomes:
measure: The change from baseline to 3 months after stimulation of Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) score
timeFrame: Baseline; 3months after stimulation
Secondary outcomes:
measure: Abnormal Involuntary Movement Scale (AIMS)
timeFrame: Baseline; 1 week, 1 month and 3months after stimulation
measure: 36-item Short-Form General Health survey (SF-36)
timeFrame: Baseline; 1 week, 1 month and 3months after stimulation
measure: Beck Depression Inventory-II (BDI)
timeFrame: Baseline; 1 week, 1 month and 3months after stimulation
measure: Beck Anxiety Inventory (BAI)
timeFrame: Baseline; 1 week, 1 month and 3months after stimulation
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: Baseline; 3months after stimulation
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB)
timeFrame: Baseline; 3months after stimulation
measure: The rate of response
timeFrame: 1 week, 1 month and 3months after stimulation
measure: The rate of adverse event (AE)
timeFrame: Within 1 week after surgery; 1 week, 1 month and 3months after stimulation
measure: Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)
timeFrame: 1 week and 1 month after stimulation
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Ruijin Hospital
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Bomin Sun
role: PRINCIPAL_INVESTIGATOR
References: