Comparison of Pallidal With Subthalamic Deep Brain Stimulation for Cervical Dystonia

Cervical Dystonia Clinical Trial

Official title:

A Randomized Controlled Trial Comparing PAllidal and SubThalamic Deep Brain Stimulation for Cervical Dystonia（the PASTS-CD Study）

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05715138
• Other study ID #: ChinaPLAGH_LB
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2023
• Est. completion date: November 30, 2026

Study information

• Verified date: July 2023
• Source: Chinese PLA General Hospital
• Contact: Zhiqi Mao, PhD
• Phone: 8618910155994
• Email: markmaoqi[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cervical dystonia (CD), also known as spasmodic torticollis, is a type of focal dystonia, mainly manifesting as involuntary head turning or tilting, or holding a twisted posture. Although it can be alleviated by injection of botulinum toxin, the effect is temporary so that patients require multiple injections. Deep Brain Stimulation (DBS) targeting on globus pallidus internus (GPi) or subthalamic nucleus (STN) has been proved to be a safe and effective strategy for primary cervical dystonia, even for those medically refractory cases. However, the question of which target is better has not been clarified.

Therefore, the invstigators design this randomized and controlled trial, aiming to compare the differences between GPi-DBS and STN-DBS for cervical dystonia in the improvement of symptoms , quality of life, mental status, cognitive status, as well as in stimulation parameters and adverse effects. The invstigators hypothesize that STN-DBS will outperform GPi-DBS at short-term follow-up, while the superiority will disappear and the efficacy of the two group will become similar at long-term follow-up.

Description:

CD limits the neck activity by involving one or a group of neck muscles and is often accompanied by pain and psychological disorders, seriously affecting the quality of life. GPi and STN are two dominant targets for DBS, either of which has been widely used in the treatment of CD with remarkable efficacy (about 50%-90% symptomatic improvement rate). However, there has been no prospective studies to directly compare the DBS efficacy of these two targets.

The invstigators plan to design a multicenter, prospective, randomized, parallel-controlled equivalent clinical trial, aiming to compare GPi-DBS with STN-DBS for drug-resistant CD in the following aspects: (1) improvement rate of dystonic symptoms, (2) improvement rate of life quality, mental and cognitive status, (3) stimulation parameters, (4) adverse effects.

According to the inclusion and exclusion criteria, a total of 98 idiopathic or hereditary isolated CD patients will be enrolled, each of whom will be randomly divided into GPi-DBS group or STN-DBS group in a 1:1 ratio by central randomization. Informed consent forms are signed and information at baseline is collected. A standardized video will be recorded to assess the severity of the disease. The DBS electrodes will be implanted into posteroventral GPi (GPi-DBS group) or dorsolateral STN (STN-DBS group) respectively. The other operation procedures and subsequent follow-up plan are the same. The DBS device will be switched on in four weeks postoperatively and the optimal stimulation parameters will be used. The invstigators will record standardized videos and/or complete a series of clinical scales (see outcome measures) for all patients at baseline, four weeks postoperatively (after activation of DBS device), three months postoperatively, six months postoperatively, and one year postoperatively. Meanwhile, the stimulation parameters and adverse effects will also be documented. Finally, two professional raters will assess the severity of CD (reflected by Toronto Western Spasmodic Torticollis Rating Scale and Tsui scale) at different timepoints according to those standardized videos in a blind manner.

Intention-to-treatment analysis and per protocol analysis are both conducted by a professional data analyst.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 98
• Est. completion date: November 30, 2026
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion criteria

1. Diagnosed as idiopathic or hereditary isolated CD;

2. Severe functional impairment;

3. Oral medication and injection of botulinum toxin become ineffective (> 3 months since last injection), or refuse to adopt botulinum toxin injection;

4. No secondary causes of CD;

5. Age 18-80 years old;

6. Normal neurological examination except for dystonia;

7. Normal brain MRI;

8. The subject or their family members can fully understand the trial and sign the informed consent;

9. Good compliance and willingness to receive regular follow-ups.

Exclusion criteria

1. Diagnosed as secondary CD;

2. CD with obvious trunk/limb involvement, or Meige syndrome;

3. History of severe mental disorders, dementia, or epilepsy;

4. Previous dystonia surgery (pallidotomy, thalamotomy, DBS, etc);

5. Accompanied by other neurological diseases (Parkinson's disease, essential tremor, multiple sclerosis, stroke, etc);

6. The patient has or needs other implantable devices (cardiac pacemakers, defibrillators, cochlear implants, spinal cord stimulators, etc);

7. Pregnant women or women who are waiting to become pregnant during the trial;

8. Poor health condition.

Related Conditions & MeSH terms

• Cervical Dystonia
• Dystonia
• Dystonic Disorders
• Torticollis

Intervention

Procedure:
• GPi-DBS
An elaborate target/trajectory planning and a precise image fusion of MRI and stereotactic CT scanning are performed before surgery. After microelectrode recording, two sets of quadripolar DBS leads (contact interval is 1.5mm) will be inserted into the posteroventral part of bilateral GPi nuclei separately. Subsequently, an implantable pulse generator will be connected via extension wires and implanted at the left/right subclavicular area subcutaneously.
• STN-DBS
An elaborate target/trajectory planning and a precise image fusion of MRI and stereotactic CT scanning are performed before surgery. After microelectrode recording, two sets of quadripolar DBS leads (contact interval is 0.5mm) will be inserted into the dorsolateral part of bilateral STN nuclei separately. Subsequently, an implantable pulse generator will be connected via extension wires and implanted at the left/right subclavicular area subcutaneously.

Device:
• GPi-DBS devices
DBS electrode: 3387 (Medtronic, Minneapolis, MN, USA) or L302 (PINS Medical, Beijing, China) or 1210(SceneRay, Suzhou, China); Extension wire: 37086 (Medtronic, Minneapolis, MN, USA) or E202 (PINS Medical, Beijing, China) or 1340/SR1341 (SceneRay, Suzhou, China); Implantable pulse generator: ACTIVA PC/RC (Medtronic, Minneapolis, MN, USA) or G102/G102R (PINS Medical, Beijing, China) or 1180/SR1101 (SceneRay, Suzhou, China).
• STN-DBS devices
DBS electrode: 3389 (Medtronic, Minneapolis, MN, USA) or L301 (PINS Medical, Beijing, China) or 1200 (SceneRay, Suzhou, China); Extension wire: 37086 (Medtronic, Minneapolis, MN, USA) or E202 (PINS Medical, Beijing, China) or 1340/SR1341 (SceneRay, Suzhou, China); Implantable pulse generator: ACTIVA PC/RC (Medtronic, Minneapolis, MN, USA) or G102/G102R (PINS Medical, Beijing, China) or 1180/SR1101 (SceneRay, Suzhou, China).

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline Toronto Western Spasmodic Torticollis Rating Scale - Severity subscale (TWSTRS-Severity) at 3 months	TWSTRS-Severity subscale can reflect the severity of the dystonia. The total score of TWSTRS-Severity subscale is 35 points. Higher scores indicate more severe symptoms.	Three months postoperatively.
Primary	Change from baseline Tsui scale at 3 months	Tsui scale can better reflect the severity of spasmodic torticollis. It consists of four parts, and the total score was calculated by A*B+C+D. The maximum score was 25 points. After treatment, a 0-10% decrease is considered ineffective, a 11%-50% decrease is considered as partial remission, a 51%-80% decrease is considered as obvious remission, and a 81%-100% decrease is considered as complete remission.	Three months postoperatively.
Primary	Change from baseline Toronto Western Spasmodic Torticollis Rating Scale - Severity subscale (TWSTRS-Severity) at 6 months	TWSTRS-Severity subscale can reflect the severity of the dystonia. The total score of TWSTRS-Severity subscale is 35 points. Higher scores indicate more severe symptoms.	Six months postoperatively.
Primary	Change from baseline Tsui scale at 6 months	Tsui scale can better reflect the severity of spasmodic torticollis. It consists of four parts, and the total score was calculated by A*B+C+D. The maximum score was 25 points. After treatment, a 0-10% decrease is considered ineffective, a 11%-50% decrease is considered as partial remission, a 51%-80% decrease is considered as obvious remission, and a 81%-100% decrease is considered as complete remission.	Six months postoperatively.
Primary	Change from baseline Toronto Western Spasmodic Torticollis Rating Scale - Severity subscale (TWSTRS-Severity) at 1 year	TWSTRS-Severity subscale can reflect the severity of the dystonia. The total score of TWSTRS-Severity subscale is 35 points. Higher scores indicate more severe symptoms.	One year postoperatively.
Primary	Change from baseline Tsui scale at 1 year	Tsui scale can better reflect the severity of spasmodic torticollis. It consists of four parts, and the total score was calculated by A*B+C+D. The maximum score was 25 points. After treatment, a 0-10% decrease is considered ineffective, a 11%-50% decrease is considered as partial remission, a 51%-80% decrease is considered as obvious remission, and a 81%-100% decrease is considered as complete remission.	One year postoperatively.
Secondary	Change of Toronto Western Spasmodic Torticollis Rating Scale - Disability subscale (TWSTRS-Disability)	TWSTRS-Disability subscale can reflect the disability of the dystonia. The total score of TWSTRS-Disability subscale is 30 points. Higher scores indicate more compromised living ability.	Three months postoperatively, six months postoperatively, and one year postoperatively.
Secondary	Change of Toronto Western Spasmodic Torticollis Rating Scale - Pain subscale (TWSTRS-Pain)	TWSTRS-Pain subscale can reflect the level of the neck pain. The total score of TWSTRS-Pain subscale is 20 points. Higher scores indicate more severe neck pain.	Three months postoperatively, six months postoperatively, and one year postoperatively.
Secondary	Change of 36-item Short Form General Health Survey (SF-36)	The SF-36 scale is a comprehensive index that reflects the health status of individuals.This scale has 8 dimensions to evaluate health-related quality of life, namely, physical function (PF), role physical (RP), body pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), mental health (MH). Higher score indicates better health status.	Six months postoperatively, and one year postoperatively.
Secondary	Change of Hamilton Anxiety Scale (HAMA)	HAMA score can better reflect the severity of anxiety. It is composed of two parts, namely, physical anxiety (item 7-13) and mental anxiety (item 1-6, 14). Total score = 29 points: severe anxiety; Total score =21 points: there must be significant anxiety; Total score =14 points: there must be anxiety; Total score = 7 points: you may have anxiety; Total score < 7 points: there are no symptoms of anxiety.	Six months postoperatively, and one year postoperatively.
Secondary	Change of 24-item Hamilton Depression Scale (HAMD)	HAMD score can better reflect the severity of depression. Total score < 7 points: normal; Total score 7-17 points: possible depression; Total score 17-24 points: definitely depression; Total score > 24 points: severe depression.	Six months postoperatively, and one year postoperatively.
Secondary	Change of Mini-mental State Examination (MMSE)	MMSE is a screening scale for Alzheimer's disease. It consists of 20 questions with 30 items (30 points), including five aspects: orientation, memory, attention and calculation, recall, language. Total score > 27 points: normal. Total score 21-27 points: mild cognitive impairment; Total score 10-20 points: moderate cognitive impairment; Total score < 9 points: severe cognitive impairment.	Six months postoperatively, and one year postoperatively.
Secondary	Change of Montreal Cognitive Assessment (MoCA)	MoCA is an assessment tool for mild cognitive impairment. The cognitive domains include attention and concentration, executive function, memory, language, visuospatial skills, abstract thinking, calculation and orientation. The total score is 30 points. A score of =26 points is considered normal.	Six months postoperatively, and one year postoperatively.
Secondary	Total electrical energy delivered (TEED)	The formula of TEED is as follows: TEED = Voltage*2*Pulse Width*Frequency/Impedance. The higher the TEED, the shorter the battery life of stimulator.	One year postoperatively.
Secondary	Adverse effects	Any adverse event occurring between the beginning time of the trial and the last follow-up.	Up to 1 year postoperatively.