The Impact of Electroacupuncture Combined With NGF on Clinical Effect and Functional Changes on Ischemic Stroke

Study Overview
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Brief Summary
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Ischemic stroke is a common clinical disease, often accompanied by motor dysfunction and cognitive impairment. At present, clinical treatment for patients with ischemic stroke recovery is limited and ineffective. The emergence of NGF has surprised the field of neurorehabilitation, but the clinical effect is not satisfactory. The main problem is that NGF is a macromolecular material with a molecular weight of 13.4 KD, which is difficult to penetrate the blood brain barrier. A large number of previous studies in our team have found that electroacupuncture with specific stimulation mode can open the blood brain barrier and induce NGF into the brain。Therefore, the purpose of this study is to investigate the effect of specific stimulation mode electroacupuncture combined with NGF treatment together with rehabilitation training on patients with ischemic stroke recovery period and to explore the mechanism of this combination therapy to improve brain function, which creates a new method and theoretical basis for nerve rehabilitation of integrated traditional Chinese and Western medicine.

Official Title
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Specific Stimulation Mode Electroacupuncture Combined With NGF for Recovery Period of Ischemic Stroke：Protocol for a Randomized Controlled Clinical Trial

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Drug: Nerver growth factor (NGF) injection
* Drug: Placebo injection
* Device: EA intervention
* Device: sham EA intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: people with first-ever ischemic stroke confirmed by CT or/and MRI; 14 days to 6 months after stroke onset; 50 years≤aged≤80 years; 3≤modified Rankin Score (mRS)≤4, and Mini-Mental State Examinations (MMSE)<27; Patients can accept treatment with EA and have good compliance; Patients have clear consciousness, pain perception and resolution ability to complete basic communication; willing to participate and be randomized to one of the groups. Exclusion Criteria: transient ischemic attack, subarachnoid hemorrhage, cerebral hemorrhage and other cerebrovascular diseases; severe heart, liver, kidney dysfunction and severe coagulation dysfunction; cerebral infarction caused by repeated recurrence of stroke, brain surgery or trauma, and brain tumors; severe neurological deficits before stroke, such as visual and auditory impairment, aphasia, agnosia, severe hemiplegia, or affected limb function before stroke, such as cerebral palsy, polio, fracture, and mRs≥1; diseases with affecting cognitive function such as congenital dementia, or alcohol, drug or substance abuse; lactation, pregnancy or intend to be pregnant within 6 months; needlesickness, needle phobia and skin infection at acupuncture site; pacemaker, implantable cardioverter defibrillator carriers or conductive metallic foreign bodies in the body; allergy to NGF; currently enrolled in another clinical trial or participation in other clinical trials within the last 3 months.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: sham EA + placebo group<br>sham EA + placebo group contain sham EA intervention and placebo injection | Drug: Placebo injection<br>* The patients will receive 1ml volume of physiological saline (PS) injected into the gluteal muscle, once a day for 4 weeks.<br>Device: sham EA intervention<br>* The only difference between sham EA intervention and EA intervention is that the stimulator is connected to the needle handle without power for 40 min intervention.<br>|
| Other: sham EA + NGF group<br>sham EA + NGF group contain sham EA intervention and NGF injection | Drug: Nerver growth factor (NGF) injection<br>* The 20ug nerve growth factor (NO.S20060051, Jinlujie) will be obtained from Hiteck Biopharmaceutical Co., Ltd, Wuhan, China. mNGF will be dissolved in 1 ml sterile water for injection and then injected intramuscularly at gluteal muscle, once a day for 4 weeks. Dose modification is not allowed for mNGF.<br>Device: sham EA intervention<br>* The only difference between sham EA intervention and EA intervention is that the stimulator is connected to the needle handle without power for 40 min intervention.<br>|
| Other: EA + placebo group<br>EA + placebo group contain EA intervention and placebo injection | Drug: Placebo injection<br>* The patients will receive 1ml volume of physiological saline (PS) injected into the gluteal muscle, once a day for 4 weeks.<br>Device: EA intervention<br>* Patients take supine position. After skin disinfection with 75% ethanol routine disinfection, the stainless needle (size 0.25mm×40mm, Hua Tuo brand, Suzhou Medical Supplies Company Ltd in Jiangsu, China) will be inserted in GV20（Baihui) and the stainless needle(size 0.25mm×25mm, described above) will be inserted in GV26 (Shuigou), acupoints will be stimulated manually until patients feel soreness, distension or heaviness (the reaction of De Qi). Then, the needles are stimulated by using an acupuncture point nerve stimulator (HANS-200, Nanjing Jinsheng, Ltd., China) with a frequency of 2/100 Hz and an intensity of 3 mA for 40 min (a homemade relay cycled power to the electrode for 6 sec on and 6 sec off), 28 days as a course of treatment, once a day.<br>|
| Other: EA + NGF group<br>EA + NGF group contain EA intervention and NGF injection | Drug: Nerver growth factor (NGF) injection<br>* The 20ug nerve growth factor (NO.S20060051, Jinlujie) will be obtained from Hiteck Biopharmaceutical Co., Ltd, Wuhan, China. mNGF will be dissolved in 1 ml sterile water for injection and then injected intramuscularly at gluteal muscle, once a day for 4 weeks. Dose modification is not allowed for mNGF.<br>Device: EA intervention<br>* Patients take supine position. After skin disinfection with 75% ethanol routine disinfection, the stainless needle (size 0.25mm×40mm, Hua Tuo brand, Suzhou Medical Supplies Company Ltd in Jiangsu, China) will be inserted in GV20（Baihui) and the stainless needle(size 0.25mm×25mm, described above) will be inserted in GV26 (Shuigou), acupoints will be stimulated manually until patients feel soreness, distension or heaviness (the reaction of De Qi). Then, the needles are stimulated by using an acupuncture point nerve stimulator (HANS-200, Nanjing Jinsheng, Ltd., China) with a frequency of 2/100 Hz and an intensity of 3 mA for 40 min (a homemade relay cycled power to the electrode for 6 sec on and 6 sec off), 28 days as a course of treatment, once a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| basic cure rate | patients with the modified Rankin Score ≤ 2 are judged as basic cure, and basic cure rate= number of patients with the modified Rankin Score ≤ 2 / group * 100 %. The modified Rankin Score ranges from 0 to 6, and the more severe the neurological deficit, the higher the score. at the end of treatment, the modified Rankin Score is recorded in all four groups. | end of treatment (week 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| simplified Fugl-Meyer Assessment of motor function score (FMA) | simplified Fugl-Meyer Assessment of motor function score sums up a total score (maximum 100 points ), including an assessment of the upper extremity (maximum 66 points) and lower extremity (maximum 34 points). Improvement in simplified Fugl-Meyer Assessment of motor function score suggests the recovery of motor function | baseline (week 0), Mid-term treatment (week 2) and end of treatment (week 4) in all four groups. | 
| Modified Barthel Index (MBI) | Modified Barthel Index is one of the measures to evaluate activities of daily living and consisted of 10 items (bathing, personal hygiene, feeding, dressing, toilet use, bladder continence, bowel control, stair climbing, chair/bed transfers and mobility. Besides, wheelchair score only if patient is unable to ambulate and is trained in wheelchair managemen). The maximum total score of Modified Barthel Index is 100, with a higher score meaning less dependent to help. | baseline (week 0), Mid-term treatment (week 2) and end of treatment (week 4) in all four groups. | 
| timed up and go test (TUGT) | timed up and go test is an assessment tool for measuring mobility in stroke patients. In the timed up and go test, each patient is asked to stand up from an armchair at height 45 cm, walk a distance of 3 m, turn, walk back to the chair, and sit back down in chair . With interval of one minute rest, a patient is required to repeat the test three times to take its mean for statistical analysis | baseline (week 0), Mid-term treatment (week 2) and end of treatment (week 4) in all four groups. | 
| Tinetti Performance Oriented Mobility Assessment (POMA) | POMA scale can be used to assess the balance with B-POMA including nine components (sitting balance, arises, attempts to arise, immediate standing balance, standing balance, nudged, eyes closed, turning 360 , and sitting down; maximum 16 points) and to evaluate the gait with G-POMA including seven components (initiation of gait, step length, step symmetry, step continuity, path, trunk, and walking stance; maximum 12 points) . A patient with POMA scored less than 24 points suggets balance dysfunction and scored less than 15 points indicates danger of falling. | baseline (week 0), Mid-term treatment (week 2) and end of treatment (week 4) in all four groups. | 
| Montreal Cognitive Assessment (MoCA) | The Montreal Cognitive Assessment is a 30-point test and focuses on assessing seven cognitive domains including visual-spatial and executive abilities, naming, delayed memory recall, attention, abstraction, language and orientation functions . A patient with MoCA scored less than 26 points suggets cognitive impairment. | baseline (week 0), Mid-term treatment (week 2) and end of treatment (week 4) in all four groups. | 
| Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) | Loewenstein Occupational Therapy Cognitive Assessment is a 91-point test to estimate cognitive functions including orientation (8 points), perception (24 points), visual movement organization (28 points), thought operation (27 points), attention and concentration (4 points). The higher the score of patients indicates the better the cognitive function. | baseline (week 0), Mid-term treatment (week 2) and end of treatment (week 4) in all four groups. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ischemic stroke, Convalescence, Electroacupuncture, nerve growth factor