Clinical trial NCT06498934: Deep Brain Stimulation of the Dentate Nucleus for Motor Rehabilitation After Stroke
Official title: Deep Brain Stimulation of Cerebellar Dentate Nucleus Promotes Upper Limb Motor Function Recovery After Ischemic Stroke: a Randomized, Double-blind, Sham-controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Stroke
Upper Extremity Paresis
Keywords: deep brain stimulation
the dentate nucleus
Lead sponsor: Beijing Municipal Administration of Hospitals
Sponsor class: OTHER_GOV
Collaborators: name: Beijing Pins Medical Co., Ltd
First posted: 2024-07-12
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind, randomized, parallel study with partial crossover (control subjects crossover to treatment after randomized portion)
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if deep brain stimulation of the dentate nucleus (DN-DBS) works to promote chronic post-stroke upper limb motor function in adults. It will also learn about the safety of DN-DBS. The main questions it aims to answer are:

Does DN-DBS paired with rehabilitation improve the upper limb motor function of participants more than rehabilitation only? What medical problems do participants have when using DN-DBS for post-stroke rehabilitation?

Researchers will compare real DN-DBS+rehabilitation to sham DN-DBS+rehabilitation (electrodes will be implanted, but no electrical current is given) to see if DN-DBS works to promote chronic post-stroke upper limb motor function.

Participants will:

Undergo unilateral DN-DBS surgery Take real DN-DBS+rehabilitation or sham DN-DBS+rehabilitation as treatment for 6 months Visit the clinic every month during the DN-DBS+rehabilitation (treatment) period for programing, checkups and tests Visit the clinic at Day 1, 30, 90 and 365 after treatment period for checkups and tests


Eligibility criteria: Inclusion Criteria:

1. Within the first year to 3 years after the first stroke;
2. Unilateral infarction located in the territory of the middle cerebral artery, but not involving the cerebellum, thalamus, and brainstem;
3. Aged 18-80 years;
4. TMS standard: TMS induces muscle evoked potential (MEP). In the contracted state of the paralyzed muscle (maximum voluntary contraction of 20-50%), a reliable standard MEP (in 5/10 trials with 50-100uv) can be induced;
5. Researchers determine the medical and neurological condition of the participant to be stable based on the participant's medical history, physical examination, and neurological examination;
6. Moderate-severe unilateral upper limb paralysis, i.e., the Fugl-Meyer Assessment (FMA-UE) scale score is ≤47;
7. The distal extremity of the limb has some degree of motor function (flexion of the elbow joint or extension of the elbow joint or partial finger flexion with FMA-UE ≥1);
8. mRS\<4 points, able to cooperate with assessment and rehabilitation;
9. No spasticity or mild spasticity in any part of the affected limb (intramuscular rotator muscle and adductor muscle of the shoulder joint, flexor muscle of the elbow joint, flexor muscle of the wrist joint or finger flexor muscle), modified Ashworth scale (MAS) \<4 points;
10. MMSE\>24 points.

Exclusion Criteria:

1. Primary hemorrhagic stroke or severe hemorrhagic conversion;
2. Any progressive neurological or somatic disease that impairs the function of the affected limb other than stroke;
3. Moderate to severe neglect or disinhibition of the affected limb;
4. Any other neurological disorder that may compromise study safety, including central nervous system vasculitis, intracranial tumors, intracranial aneurysms, multiple sclerosis, or arteriovenous malformations;
5. Pain intensity on the affected limb NRS ≥5 or severe sensory disturbance, NIHSS (item 8) = 2;
6. Exclusion of cardioembolic stroke, patients requiring long-term anticoagulation;
7. Unable to stop anticoagulation treatment at least 10 days prior to surgery (i.e., antiplatelet and/or anticoagulant therapy);
8. Seizure(s) after stroke or potential risk of seizure(s);
9. Switching to oral spasticity medication within 2 weeks of enrollment, or injection of botulinum toxin in the affected arm within 4 months, and/or intention to start taking spasticity medication or inject botulinum toxin during the study follow-up period or within 12 months after implantation;
10. The presence of active psychosis that may affect treatment effect, such as psychosis or severe personality disorder;
11. Untreated or inadequately treated depression, i.e., Beck Depression Inventory score of 20 or more at admission;
12. Diagnosis of dementia;
13. Uncontrolled hypertension or history of cardiovascular disease for a long time;
14. MRI contraindications, such as implanted metal devices or electronic devices (pacemakers, defibrillators, spinal cord stimulators);
15. Participated in another device, biological, or drug study within 30 days of consenting to participate in the current study;
16. Non-pregnant or fertile women must use acceptable contraception, and pregnant women are excluded or terminated from the study;
17. Received decompressive craniectomy;
18. The patient has severe cerebral small vessel disease, basilar artery vascular disease, and/or any other structural abnormalities of the cerebellum, cerebellar peduncles, and brainstem that prevent safe placement of DBS;
19. The investigator determines that the patient has a condition that would significantly increase the risk of study non-compliance, study safety, and/or study integrity. For the safety of the subject, for example, if the subject experiences an exacerbation of their condition, a serious adverse event, or poor compliance.

Primary outcomes:
measure: Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change at Day 1
timeFrame: V6, One day after 6-months of therapy
Secondary outcomes:
measure: Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change at Day 90
timeFrame: V8, 90 days after 6-months of therapy
measure: Wolf Motor Function Test (WMFT) Average Change at Day 1
timeFrame: V6, One day after 6-months of therapy
measure: Wolf Motor Function Test (WMFT) Average Change at Day 90
timeFrame: V8, 90 days after 6-months of therapy
measure: Action Research Arm Test (ARAT) Average Change at Day 1
timeFrame: V6, One day after 6-months of therapy
measure: Action Research Arm Test (ARAT) Average Change at Day 90
timeFrame: V8, 90 days after 6-months of therapy
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital
Study officials:
affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
name: Jianguo Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
name: Zixiao Li, MD
role: PRINCIPAL_INVESTIGATOR
References: