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

Ischemic Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05231694
• Other study ID #: XLin
• Status: Recruiting
• Phase: Phase 4
• Start date: April 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2022
• Source: The Third Affiliated hospital of Zhejiang Chinese Medical University
• Contact: xianming Lin, PHD
• Phone: +86-13858028101
• Email: linxianming1966[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 288
• Est. completion date: December 31, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Nerver growth factor (NGF) injection
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.
• Placebo injection
The patients will receive 1ml volume of physiological saline (PS) injected into the gluteal muscle, once a day for 4 weeks.

Device:
• EA intervention
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.
• sham EA intervention
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.

Locations

Country	Name	City	State
China	The Third Affiliated Hospital of Zhejiang Chinese Medical University	Hangzhou	Zhejiang

Sponsors (3)

Lead Sponsor	Collaborator
The Third Affiliated hospital of Zhejiang Chinese Medical University	Hwamei Hospital of Ningbo, second people hospital of lishui

Country where clinical trial is conducted

China, 

References & Publications (16)

Baber N. International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH). Br J Clin Pharmacol. 1994 May;37(5):401-4. — View Citation

Broderick JP, Adeoye O, Elm J. Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials. Stroke. 2017 Jul;48(7):2007-2012. doi: 10.1161/STROKEAHA.117.017866. Epub 2017 Jun 16. Review. — View Citation

Byun K, Hyodo K, Suwabe K, Ochi G, Sakairi Y, Kato M, Dan I, Soya H. Positive effect of acute mild exercise on executive function via arousal-related prefrontal activations: an fNIRS study. Neuroimage. 2014 Sep;98:336-45. doi: 10.1016/j.neuroimage.2014.04 — View Citation

Cai Y, Zhang CS, Ouyang W, Li J, Nong W, Zhang AL, Xue CC, Wen Z. Electroacupuncture for poststroke spasticity (EAPSS): protocol for a randomised controlled trial. BMJ Open. 2018 Feb 27;8(2):e017912. doi: 10.1136/bmjopen-2017-017912. — View Citation

Cao Y, Yu S, Zhang Q, Yu T, Liu Y, Sun Z, Zhao M, Wang W, Zhao JZ; Chinese Stroke Association Stroke Council Guideline. Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinic — View Citation

Chu JJ, Chen XJ, Shen SS, Zhang XF, Chen LY, Zhang JM, He J, Zhao JF. A poor performance in comprehensive geriatric assessment is associated with increased fall risk in elders with hypertension: a cross-sectional study. J Geriatr Cardiol. 2015 Mar;12(2):1 — View Citation

Cope M, Delpy DT. System for long-term measurement of cerebral blood and tissue oxygenation on newborn infants by near infra-red transillumination. Med Biol Eng Comput. 1988 May;26(3):289-94. — View Citation

Fugl-Meyer AR, Jääskö L, Leyman I, Olsson S, Steglind S. The post-stroke hemiplegic patient. 1. a method for evaluation of physical performance. Scand J Rehabil Med. 1975;7(1):13-31. — View Citation

Huang J, Lin Z, Wang Q, Liu F, Liu J, Fang Y, Chen S, Zhou X, Hong W, Wu J, Madrigal-Mora N, Zheng G, Yang S, Tao J, Chen L. The effect of a therapeutic regimen of Traditional Chinese Medicine rehabilitation for post-stroke cognitive impairment: study pro — View Citation

Larsson AC, Palstam A, Persson HC. Physical Function, Cognitive Function, and Daily Activities in Patients Hospitalized Due to COVID-19: A Descriptive Cross-Sectional Study in Sweden. Int J Environ Res Public Health. 2021 Nov 4;18(21). pii: 11600. doi: 10 — View Citation

Lu H, Zhang T, Wen M, Sun L. Impact of repetitive transcranial magnetic stimulation on post-stroke dysmnesia and the role of BDNF Val66Met SNP. Med Sci Monit. 2015 Mar 14;21:761-8. doi: 10.12659/MSM.892337. — View Citation

Son H, Park C. Effect of turning direction on Timed Up and Go test results in stroke patients. Eur J Phys Rehabil Med. 2019 Feb;55(1):35-39. doi: 10.23736/S1973-9087.18.05202-4. Epub 2018 Jul 6. — View Citation

Yu KW, Lin CL, Hung CC, Chou EC, Hsieh YL, Li TM, Chou LW. Effects of electroacupuncture on recent stroke inpatients with incomplete bladder emptying: a preliminary study. Clin Interv Aging. 2012;7:469-74. doi: 10.2147/CIA.S37531. Epub 2012 Nov 8. — View Citation

Zhao N, Zhang H, Liu T, Liu J, Xiang Y, Shu G, Li C, Xie J, Chen L. Neuromodulatory Effect of Sensorimotor Network Functional Connectivity of Temporal Three-Needle Therapy for Ischemic Stroke Patients with Motor Dysfunction: Study Protocol for a Randomize — View Citation

Zhao W, You H, Jiang S, Zhang H, Yang Y, Zhang M. Effect of Pro-kin visual feedback balance training system on gait stability in patients with cerebral small vessel disease. Medicine (Baltimore). 2019 Feb;98(7):e14503. doi: 10.1097/MD.0000000000014503. — View Citation

Zhen X, Sun X, Dong H. Health Technology Assessment and Its Use in Drug Policies in China. Value Health Reg Issues. 2018 May;15:138-148. doi: 10.1016/j.vhri.2018.01.010. Epub 2018 May 3. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.