SUNDYS: A Multicenter, Randomized, Double-blind, Sham-controlled, Parallel-group Trial (SUNDYS)

Subthalamic Nucleus Deep Brain Stimulation in Isolated Generalized or Segmental Dystonia: A Multicenter, Randomized, Double-blind, Sham-controlled, Parallel-group Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Dystonia
• Intervention / Treatment: Procedure: Deep brain stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kejia Hu, MD, PhD; Phone Number: 18930113801; Email: dockejiahu@gmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Shanghai Ruijin Hospital
      • Contact: Kejia Hu, MD,PhD; Phone Number: +86 18930113801; Email: dockejiahu@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: STN DBS stimulation group; In the STN DBS stimulation group, patients will receive a continuous DBS stimulation for 3 months and the first default parameters applied will be monopolar setting (0.5 V under threshold that causes side effects, 135 Hz, 90 µs, at one of the two dorsal contacts). If the default parameters are found not suitable for an individual patient due to unexpected reasons, an alternative method will be applied (e.g., decreased voltage) to try to maintain full compliance with the scheduled study.	Procedure: Deep brain stimulation; Deep brain stimulation (DBS) has been in use to treat patients with movement disorders since 1989, with many thousands of publications showing its effectiveness. DBS for dystonia received the US FDA mark in 2003 and China FDA mark in 2016. In this study, the DBS system devices are manufactured and donated by SceneRay (Suzhou, China). The Stimulator System is implanted by a qualified neurosurgeon and consists of three implantable components: the leads, the extension wires and the neurostimulator. The DBS programming will start within 1 week after the surgery completed.
Sham Comparator: Sham stimulation group; In the sham stimulation group, the programming will also start within 1 week after the surgery, but at each follow-up the DBS system will be turned off after the parameter is adjusted to the threshold that causes side effects without continuous stimulation. After the 3-month double-blind period the patients can choose to set on the DBS system again and receive regular continuous stimulation treatment.	Procedure: Deep brain stimulation; Deep brain stimulation (DBS) has been in use to treat patients with movement disorders since 1989, with many thousands of publications showing its effectiveness. DBS for dystonia received the US FDA mark in 2003 and China FDA mark in 2016. In this study, the DBS system devices are manufactured and donated by SceneRay (Suzhou, China). The Stimulator System is implanted by a qualified neurosurgeon and consists of three implantable components: the leads, the extension wires and the neurostimulator. The DBS programming will start within 1 week after the surgery completed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change from baseline to 3 months after stimulation of Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) score	The scale consists of a movement and disability subscale with scores ranging from 0 to 120 and 0 to 30, respectively, higher scores indicating greater impairment.	Baseline; 3months after stimulation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abnormal Involuntary Movement Scale (AIMS)	The AIMS is a 12-item clinician-rated scale to assess severity of dyskinesias. These items are rated on a five-point scale of severity from 0-4. The scale is rated from 0 (none), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). Two of the 12 items refer to dental care.	Baseline; 1 week, 1 month and 3months after stimulation
36-item Short-Form General Health survey (SF-36)	SF-36 is a measure of health-related quality-of-life with a 36-item patient-reported questionnaire that covers eight health domains. Higher scores indicate a more favorable health state.	Baseline; 1 week, 1 month and 3months after stimulation
Beck Depression Inventory-II (BDI)	BDI contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms.	Baseline; 1 week, 1 month and 3months after stimulation
Beck Anxiety Inventory (BAI)	BAI contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe anxiety symptoms.	Baseline; 1 week, 1 month and 3months after stimulation
Montreal Cognitive Assessment (MoCA)	MoCA scores range between 0 and 30. A score of 26 or over is considered to be normal. Lower scores indicate more disability.	Baseline; 3months after stimulation
Cambridge Neuropsychological Test Automated Battery (CANTAB)	A detailed computerized cognitive battery selected from CANTAB includes: Stockings of Cambridge (SOC) and Spatial working memory (SWM) for executive function; Motor screening task (MOT) and a five-choice series selection task for attention; Paired associates learning (PAL) and Pattern recognition memory (PRM) for memory.	Baseline; 3months after stimulation
The rate of response	The number of patients with ≥30% improvement in the movement score on the BFMDRS	1 week, 1 month and 3months after stimulation
The rate of adverse event (AE)		Within 1 week after surgery; 1 week, 1 month and 3months after stimulation
Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)	The scale consists of a movement and disability subscale with scores ranging from 0 to 120 and 0 to 30, respectively, higher scores indicating greater impairment.	1 week and 1 month after stimulation

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: West China Hospital; Renmin Hospital of Wuhan University; Second Affiliated Hospital of Soochow University; Shanghai Tongji Hospital, Tongji University School of Medicine
• Investigators: Principal Investigator: Bomin Sun, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: November 25, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 3, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Subthalamic nucleus; Deep brain stimulation
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Dystonia; Dystonic Disorders
• Other Study ID Numbers: Ruijin_SUNDYS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No