Effect of Specific Mode Electroacupuncture Stimulation Combined with NGF on Dysphagia After Ischaemic Stroke: a Pilot Randomized Controlled Trial

Overview

Ischemic stroke is a common clinical disease, often accompanied by dysphagia. At present, clinical treatment for patients with dysphagia after ischemic stroke is limited. 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 mode electroacupuncture stimulation combined with NGF treatment on patients with dysphagia after ischemic stroke 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.

Interventions

• Drug Nerver growth factor (NGF) injection
  The 20ug mouse nerve growth factor (NO. S20060051, Jinlujie) will be obtained from Hiteck Biopharmaceutical Co., Ltd., Wuhan, China. mNGF will be dissolved in 2 ml of sterile water for injection and then injected intramuscularly into the gluteal muscle, three times a week for 6 weeks.
• Drug Placebo injection
  Patients will receive 2ml volume of physiological saline (PS) injected intramuscularly into the gluteal muscle, three times a week for 6 weeks.
• Device EA intervention
  Patients take supine position. After skin disinfection with 75% ethanol routine disinfection, the stainless needle (size 0.25mm×40mm, Hwato 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 acupu
• Device Acupuncture intervention
  Patients take supine position. After skin disinfection with 75% ethanol routine disinfection, the stainless needle (size 0.25mm×40mm, Hwato 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 connected to an acupuncture

Primary outcome measures

• Functional Oral Intake Scale (FOIS) [Time frame: week 0, week 2, week 4, week 6, week 12]

Secondary outcome measures (5)

• Dysphagia Outcome and Severity Scale (DOSS) [Time frame: week 0, week 6]
• Penetration Aspiration Scale (PAS) [Time frame: week 0, week 6]
• modified Rankin Scale (mRS) [Time frame: week 0, week 2, week 4, week 6]
• Modified Barthel Index (MBI) [Time frame: week 0, week 2, week 4, week 6]
• Oxygenated hemoglobin and deoxygenated hemoglobin in cerebral cortex [Time frame: week 0, week 6]

Eligibility criteria

Inclusion criteria

• Patients with first-ever ischemic stroke confirmed by Computed Tomography (CT) and/or Magnetic Resonance Imaging (MRI);
• Onset time ranged from 15 days to 180 days;
• Aged 18 to 80 years old, male or female;
• Dysphagia confirmed by a videofluoroscopic swallowing study (VFSS);
• Patients who are able to accept and comply with acupuncture, electroacupuncture treatment, gluteal intramuscular injection, and have good compliance;
• Have provided signed consent and exhibit willingness to participate in the trial.
• Women who are lactating, pregnant or intending to get pregnant;

Exclusion criteria

• Patients with dysphagia before ischemic stroke onset or dysphagia not caused by ischemic stroke;
• Patients with severe cognitive impairment;
• Patients with severe cardiac, hepatic, and renal dysfunction, as well as severe coagulation abnormalities;
• Patients with other abnormal test results who are deemed unsuitable to participate in this study by the investigator.
• Multiple occurrences of stroke, or a history of craniocerebral surgery, or cerebral infarction caused by trauma or brain tumors.
• Patients with severe neurological deficits prior to ischemic stroke, such as visual and auditory impairments, aphasia, agnosia, severe hemiplegia, and other conditions.
• Women who are lactating, pregnant or intending to get pregnant;
• Patients with a history of needle fainting or with skin infections at the acupuncture site.
• Cardiac pacemaker carrier;
• Patients allergic to NGF;
• The inability to undergo VFSS;
• Patients with a medication history that may alter cortical excitability within the past 2 months.
• Patients who are currently participating in other clinical trials or have participated in clinical trials that ended within the last 3 months.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

China · 1 center

• The Third Affiliated Hospital of Zhejiang Chinese Medical University — Hangzhou

Publications

• Fu X, Li H, Yang W, Li X, Lu L, Guo H, Guo K, Huang Z. Electroacupuncture at HT5 + GB20 promotes brain remodeling and significantly improves swallowing function in patients with stroke. Front Neurosci. 2023 Nov 2;17:1274419. doi: 10.3389/fnins.2023.1274419. eCollection 2023. PMID 38027487
• Dai M, Qian K, Ye Q, Yang J, Gan L, Jia Z, Pan Z, Cai Q, Jiang T, Ma C, Lin X. Specific Mode Electroacupuncture Stimulation Mediates the Delivery of NGF Across the Hippocampus Blood-Brain Barrier Through p65-VEGFA-TJs to Improve the Cognitive Function of MCAO/R Convalescent Rats. Mol Neurobiol. 2025 Feb;62(2):1451-1466. doi: 10.1007/s12035-024-04337-8. Epub 2024 Jul 12. PMID 38995444
• Lin Y, Gan L, Ren L, Ma C, Dai M, Qian K, Ye Q, Lin X. Acupuncture with specific mode electro-stimulation effectively and transiently opens the BBB through Shh signaling pathway. Neuroreport. 2023 Dec 13;34(18):873-886. doi: 10.1097/WNR.0000000000001970. Epub 2023 Nov 8. PMID 37942738
• Sheng L, Yin L, Peng D, Zhao L. From Best Evidence to Best Practice: Enteral Nutrition from Continuous Nasal Feeding in Stroke Patients. Int J Gen Med. 2020 Oct 22;13:927-936. doi: 10.2147/IJGM.S269393. eCollection 2020. PMID 33132703
• Zhang H, Park JH, Maharjan S, Park JA, Choi KS, Park H, Jeong Y, Ahn JH, Kim IH, Lee JC, Cho JH, Lee IK, Lee CH, Hwang IK, Kim YM, Suh YG, Won MH, Kwon YG. Sac-1004, a vascular leakage blocker, reduces cerebral ischemia-reperfusion injury by suppressing blood-brain barrier disruption and inflammation. J Neuroinflammation. 2017 Jun 23;14(1):122. doi: 10.1186/s12974-017-0897-3. PMID 28645333
• Gutierrez-Fernandez M, Fuentes B, Rodriguez-Frutos B, Ramos-Cejudo J, Vallejo-Cremades MT, Diez-Tejedor E. Trophic factors and cell therapy to stimulate brain repair after ischaemic stroke. J Cell Mol Med. 2012 Oct;16(10):2280-90. doi: 10.1111/j.1582-4934.2012.01575.x. PMID 22452968
• Barbero P, Busso M, Tinivella M, Artusi CA, De Mercanti S, Cucci A, Veltri A, Avagnina P, Calvo A, Chio' A, Durelli L, Clerico M. Long-term follow-up of ultrasound-guided botulinum toxin-A injections for sialorrhea in neurological dysphagia. J Neurol. 2015 Dec;262(12):2662-7. doi: 10.1007/s00415-015-7894-1. Epub 2015 Sep 26. PMID 26410746
• Rofes L, Muriana D, Palomeras E, Vilardell N, Palomera E, Alvarez-Berdugo D, Casado V, Clave P. Prevalence, risk factors and complications of oropharyngeal dysphagia in stroke patients: A cohort study. Neurogastroenterol Motil. 2018 Mar 23:e13338. doi: 10.1111/nmo.13338. Online ahead of print. PMID 29573064

Identifiers

NCT: NCT06737549 · ZSLL-KY-2024-074-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗