Clinical trial NCT05968248: Efficacy and Safety of Deep Brain Stimulation in Mesencephalic Locomotor Region（MLR） for Poststroke Hemiplegia
Official title: A Randomized Controlled Trial Exploring the Efficacy and Safety of Deep Brain Stimulation in the Treatment of Motor Dysfunction After Stroke#the PASTS-Stroke Study#
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Stroke Sequelae
Keywords: Deep brain stimulation;
Hemiplegia;
Motor recovery;
Stroke.
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2023-08-01
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Abstract: Background: The leftover movement disorder of stroke patients is one of the main causes of disability, and there is still no specific solution. Studies have shown that the improvement of movement disorder symptoms in patients receiving DBS is a potential therapy. treatment approach. However, at present, there are few large-sample studies in this area at home and abroad, which cannot well reveal its actual therapeutic effect and safety, and do not fully understand its potential neural mechanisms, so it is impossible to form a unified and standardized treatment standard, which limits its wide application in clinical practice. Objectives: This study aimed to determine the efficacy and safety of hemiplegia recovery after deep brain electrical stimulation in stroke patients with hemiplegia. Methods/Design: This was a double-blind randomized cross-over controlled pilot study in which 62 patients were assigned to receive deep brain stimulation (DBS) and randomized into DBS and control groups using a randomized controlled study approach, DBS group One month after the operation, electrical stimulation was started, and the control group was given sham stimulation treatment. After 3 and 6 months of follow-up, all the machines were turned off. After a 2-week washout period, the control group was turned on, but the DBS group was given sham stimulation. After the 9th and 12th month of follow-up, all patients were given start-up treatment, and neuroimaging and various post-stroke motor-related scores were performed for data collection and analysis. Discussion: The investigators propose a research design and rationale to explore the effectiveness and safety of DBS in patients with post-stroke hemiplegia, and provide evidence and reference for DBS in the treatment of post-stroke dyskinesia. Study limitations are related to the small sample size and short study time period.

Detailed description: The incidence of stroke has been more than 20 million stroke patients worldwide, and it has become the third highest burden disease in the world.The disability rate of stroke is as high as 60-80%. The movement disorder left by the disease is the main reason for the high burden of the disease. At present, there is no particularly obvious and effective treatment measure in clinical practice. If it is not treated in time, it may lead to permanent disability. The high cost of traditional rehabilitation and the fatigue of rehabilitation training institutions and family commuting make it difficult for patients to adhere to treatment, and the treatment effect is poor.Deep Brain Stimulation (DBS) therapy has achieved good therapeutic effects in many diseases that were considered difficult to treat in the past, such as Parkinson's, depression and other diseases , so it is applied to In the treatment of motor function recovery after stroke , many animal experiments and human clinical studies have confirmed its efficacy .However, the efficacy and safety of DBS in the treatment of poststroke motor dysfunction have not been verified by clinical randomized controlled trials.

The invstigators plan to design a multicenter, prospective, randomized, parallel- controlled equivalent clinical trial, aiming to to explore the efficacy and safety of DBS in the treatment of motor dysfunction after stroke in the following aspects: (1) improvement rate of hemiplegia after stroke (2) improvement rate of life quality, mental and cognitive status, (3)stimulation parameters, (4) adverse effects.

The main purpose of our design of this study was to provide more clinical evidence for the use of deep brain stimulation (DBS) in patients with post-stroke motor dysfunction. The primary objective was to determine the effectiveness and safety of deep brain stimulation (DBS) for improving motor dysfunction in stroke patients. The secondary purpose is to explore the mechanism of deep brain stimulation (DBS) in the treatment of neurological function of post-stroke motor impairment and the improvement of the quality of life and psychosocial status of patients.

According to the inclusion and exclusion criteria,the investigators aimed to collect 62 patients who were diagnosed with stroke and left with motor dysfunction. All patients included in the study will undergo DBS implantation after baseline assessment, and then will be randomly divided into 2 groups at a ratio of 1:1: DBS treatment group and conventional rehabilitation group. The DBS electrodes will be implanted into MLR.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, one month 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 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.

Eligibility criteria: Inclusion Criteria:

1. Meet WHO or international diagnostic criteria for stroke disease;
2. The first unilateral supratentorial ischemic or hemorrhagic stroke, the condition is stable after acute treatment of ischemic stroke, the course of disease is 6 months ≤ 1 year, and participate in 2 evaluations (screening and baseline) before enrollment.
3. Diagnosed by professional physicians combined with brain CT or magnetic resonance imaging and other imaging techniques;
4. Between the ages of 18 and 80, male or female
5. The responsible lesion in the unilateral white matter area indicated by cranial CT or MRI
6. Relevant sequelae such as limb dysfunction after stroke, accompanied by unilateral limb motor dysfunction, proved to be right-handed by standardized examination.
7. National Institutes of Health Stroke Scale (NIHSS) score from 2 to 20, grades paralyzed muscle strength, between grades 1 and 4, WISCI II, grade \>2 (0-20 items): Assisted by one or more persons, able to walk at least 10 m, and less responsive to conventional rehabilitation prior to inclusion.
8. Perfect clinical data
9. Stable medical and physical condition with adequate nursing support and appropriate medical care in the patient's home community.
10. The patient himself or voluntarily signs the informed consent and is willing to cooperate with relevant treatment

Exclusion Criteria:

1. Glasgow Coma Scale (GSC) score below 15, Minimum Mental State Examination (MMSE) assessment for dementia indicated, suffering from mental disturbance and unable to cooperate with examination or treatment.
2. Motor and sensory disturbances are not induced by stroke, nor by previous ischemic stroke, but stroke induced by trauma, brain tumor, etc.
3. Serious comorbidities, such as malignant tumors, primary heart, liver, kidney or hematopoietic system diseases.
4. History of cognitive impairment, mental disorder, drug abuse, drug allergy, and alcoholism.
5. Infection or rupture of the skin on the forearm or leg.
6. Possess a pacemaker, metal stent, plate, or implant susceptible to electrical impulses in the body (pacemaker or defibrillator, baclofen pump, deep brain stimulator, Ventricular shunts, shrapnel, etc.).
7. Pregnant or breast-feeding or have a recent birth plan.
8. IS CLASSROUS.
9. Congenital or acquired abnormalities of lower extremities (affecting joints and bones).
10. Registration of investigators, their family members, employees, and other dependents.
11. Severe joint contractures cause loss or limitation of lower limb activities.
12. Blood system diseases with increased risk of bleeding during surgical intervention.
13. Participate in another study drug study within 30 days before and during this study.
14. Unable to complete the basic process, or difficult to maintain compliance and follow-up.

Primary outcomes:
measure: Motor function intervention effect: Fugl-Meyer Assessment Scale (FMA)
timeFrame: Up to 1 year postoperatively
Secondary outcomes:
measure: Overall improvement of clinical symptoms
timeFrame: Up to 1 year postoperatively
measure: Balance ability
timeFrame: Up to 1 year postoperatively
measure: Walking function
timeFrame: Up to 1 year postoperatively
measure: Fall risk
timeFrame: Up to 1 year postoperatively
measure: ADL executive ability
timeFrame: Up to 1 year postoperatively
measure: A 36-item short-form questionnaire (SF-36)
timeFrame: Up to 1 year postoperatively
measure: The incidence of surgical complications and side effects
timeFrame: Up to 1 year postoperatively
measure: Hamilton Depression Scale，HAMD
timeFrame: Up to 1 year postoperatively
measure: Acceptability of the intervention
timeFrame: Up to 1 year postoperatively
measure: Hamilton Anxiety Scale (HAMA)
timeFrame: Up to 1 year postoperatively
measure: All adverse events
timeFrame: Up to 1 year postoperatively
Other outcomes:
Locations:
Study officials:
affiliation: Chinese PLA General Hospital
name: Zhiqi Mao, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese PLA General Hospital
name: Junpeng Xu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chinese PLA General Hospital
name: Bin Liu, PhD
role: STUDY_CHAIR
affiliation: Chinese PLA General Hospital
name: Di Liu, MD
role: STUDY_CHAIR
affiliation: Chinese PLA General Hospital
name: Haonan Yang, MD
role: STUDY_CHAIR
affiliation: Chinese PLA General Hospital
name: Shufeng Liang, MD
role: STUDY_CHAIR
affiliation: Chinese PLA General Hospital
name: Zhebin Feng, MD
role: STUDY_CHAIR
affiliation: Chinese PLA General Hospital
name: Jun Hong, MD
role: STUDY_CHAIR
affiliation: Chinese PLA General Hospital
name: Rui Hui, MD
role: STUDY_CHAIR
References: