Deep Brain Stimulation of the Dentate Nucleus for Motor Rehabilitation After Stroke

Deep Brain Stimulation of Cerebellar Dentate Nucleus Promotes Upper Limb Motor Function Recovery After Ischemic Stroke: a Randomized, Double-blind, Sham-controlled Trial

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

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke; Upper Extremity Paresis
• Intervention / Treatment: Other: Rehabilitation; Device: deep brain stimulation

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tao Xue, MD; Phone Number: 86-18550213165; Email: 2992326676@qq.com

Study Locations

• China
  • Beijing, China, 100070
    • Beijing Tiantan Hospital
    • Contact: Tao Xue, MD; Phone Number: 86-18550213165; Email: 2992326676@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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
Experimental: real DN-DBS + rehabilitation; Study treatment is deep brain stimulation of the dentate nucleus (DN-DBS) delivered during 6-month rehabilitation period.	Other: Rehabilitation; Rehabilitation movements to improve upper limb function after stroke; Device: deep brain stimulation; Stimulation of the dentate nucleus that is paired with upper limb rehabilitation movements.
Active Comparator: sham DN-DBS + rehabilitation; Active control treatment is rehabilitation (standard-of-care treatment) with sham DN-DBS (electrode implanted but won't turn on the device).	Other: Rehabilitation; Rehabilitation movements to improve upper limb function after stroke

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change at Day 1	The Fugl-Meyer Assessment, Upper Limb (FMA-UE) was analyzed for difference in average change at Day-1 after 6-months of therapy compared to baseline (Difference in average change in FMA-UE from baseline [V0] to one day after therapy [V6]). FMA-UE was collected at each visit. The FMA-UE is a common scale used to measure motor impairment after a stroke. The range is 0 (more impairment) to 66 (no impairment).	V6, One day after 6-months of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fugl-Meyer Assessment, Upper Limb (FMA-UE) Average Change at Day 90	The Fugl-Meyer Assessment, Upper Limb (FMA-UE) was analyzed for difference in average change at Day-90 after 6-months of therapy compared to baseline (Difference in average change in FMA-UE from baseline [V0] to 90 days after therapy [V8]). FMA-UE was collected at each visit. The FMA-UE is a common scale used to measure motor impairment after a stroke. The range is 0 (more impairment) to 66 (no impairment).	V8, 90 days after 6-months of therapy
Wolf Motor Function Test (WMFT) Average Change at Day 1	The Wolf Motor Function Test (WMFT) is an assessment scale of upper extremity functional level after stroke. The functional assessment range is an average of 15 sub-items with a range from 0 to 5, with 0 (meaning did not attempt) to 5 (meaning normal). WMFT Day 1 - is a measure of the functional assessment change from baseline to one day after 6-months of therapy.	V6, One day after 6-months of therapy
Wolf Motor Function Test (WMFT) Average Change at Day 90	The Wolf Motor Function Test (WMFT) is an assessment scale of upper extremity functional level after stroke. The functional assessment range is an average of 15 sub-items with a range from 0 to 5, with 0 (meaning did not attempt) to 5 (meaning normal). WMFT Day 90 - is a measure of the functional assessment change from baseline to 90 days after 6-months of therapy.	V8, 90 days after 6-months of therapy
Action Research Arm Test (ARAT) Average Change at Day 1	Action Research Arm Test (ARAT) is a common scale of fine movements of distal upper limbs after stroke. The functional assessment range is an average of 19 sub-items with a range from 0 to 3, with 0 (meaning did not attempt) to 5 (meaning normal). ARAT Day 1 - is a measure of the functional assessment change from baseline to one day after 6-months of therapy.	V6, One day after 6-months of therapy
Action Research Arm Test (ARAT) Average Change at Day 90	Action Research Arm Test (ARAT) is a common scale of fine movements of distal upper limbs after stroke. The functional assessment range is an average of 19 sub-items with a range from 0 to 3, with 0 (meaning did not attempt) to 5 (meaning normal). ARAT Day 90 - is a measure of the functional assessment change from baseline to 90 days after 6-months of therapy.	V8, 90 days after 6-months of therapy

Collaborators and Investigators

• Sponsor: Beijing Municipal Administration of Hospitals
• Collaborators: Beijing Pins Medical Co., Ltd
• Investigators: Principal Investigator: Jianguo Zhang, MD, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Principal Investigator: Zixiao Li, MD, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: July 5, 2024
• First Submitted That Met QC Criteria: July 5, 2024
• First Posted (Actual): July 12, 2024

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: deep brain stimulation; the dentate nucleus
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Stroke; Paresis
• Other Study ID Numbers: HX-A-2024030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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