Randomized Controlled Study of Optical 3D Navigated Repetitive Transcranial Magnetic Stimulation for Achalasia.

Not Applicable

Not yet recruiting

• Conditions: Vagus Nerve Motor Disorder; Transcranial Magnetic Stimulation, Repetitive; Esophageal Achalasia; Functional Magnetic Resonance Imaging
• Interventions: Device: Sham; Device: Repetitive transcranial magnetic stimulation

• Registration Number: NCT06027190
• Lead Sponsor: Zhang Nina

Brief Summary

The goal of this clinical trial is to investigate the clinical efficacy of repetitive transcranial magnetic stimulation in the treatment of achalasia in patients diagnosed with achalasia by comprehensive evaluation of clinical symptoms, HREM, and barium meal examination, optimize rTMS treatment parameters, and provide an effective and noninvasive new treatment strategy for achalasia. The main questions it aims to answer are:

1. To investigate the clinical efficacy of individualized treatment of achalasia with optical 3D navigation repetitive transcranial magnetic stimulation.

2. Optimize rTMS parameters to achieve the best clinical treatment.

Participants will need to fill out the Eckardt score scale and SF-36 quality of life scale, undergo cranial T1 structural magnetic resonance for functional connectivity analysis, and select the brain region with the strongest positive functional connectivity to the DMV as the rTMS target. All patients were randomly divided into four groups: sham-rTMS group, 5Hz-rTMS group, 10Hz-rTMS group, and 30Hz-rTMS group, and each group received acute and chronic stimulation, respectively. In the acute stimulation stage, patients only need to do rTMS once, and HREM and HRV detection are given before and after rTMS (stimulation for 1s, interval for 4s, 10 pulses per second, receiving a total of 3000 pulses); in the chronic stimulation stage, patients receive 25 minutes of rTMS actual stimulation or sham stimulation each time, lasting for 20 times, which is completed within 30 days, and the actual stimulation parameters are the same as those of acute stimulation, and the sham stimulation coil is consistent with the appearance and sound of proper stimulation, but there is no substantial stimulation. High-definition esophageal manometry, timed barium meal, heart rate coefficient of variation, and serum neurotransmitters were performed before and after chronic stimulation. Finally, a weekly telephone follow-up was performed for 12 weeks, including Eckardt score and SF-36 quality of life scale.

Detailed Description

Study hypothesis: By analyzing the strongest resting-state functional connectivity between DMV and right precentral gyrus, left postcentral gyrus, and left brain leads in achalasia patients, individualized rTMS treatment with optical 3D navigation was applied to relax LES and relieve the clinical symptoms of dysphagia.

Statistical methods: SPSS 25.0 software was used to process the data, symptom score, manometry parameters, serum transmitters and other quantitative indicators. If they met the normal distribution, they were expressed as Mean ± SD. The t-test was performed for the comparison between the two groups; if they did not obey the normal distribution, the median (quartile) was used for statistical description. The rank sum test was used for the comparison between the two groups. Enumeration data were described using number of cases (percentage), and X2 test, corrected X2 test, or Fisher exact test were performed for comparison between the 2 groups.

Study Timeline

• Study First Submitted: 2023-08-31
• Status Verified: 2023-09
• Study First Submitted QC: 2023-09-06
• Study First Posted: 2023-09-07
• Last Update Submitted: 2023-09-15
• Last Update Posted: 2023-09-21
• Study Start: 2024-01-01
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

• Aged more than 18 years old, less than 75 years old;
• Clinical symptoms evaluation, HREM, esophageal barium meal examination confirmed the diagnosis of achalasia;
• Willing to sign informed consent.

Exclusion Criteria

• Presence of metal hardware in close contact with the discharge coil (e.g., cochlear implant, internal pulse generator, or drug pump). Note: Cochlear implants include electrodes, magnets, loop antennas, and electronic chips under the scalp implanted in the cochlea;
• Intracranial metal implants;
• Patients with cardiac pacemakers, vagal nerve stimulation (VNS) systems, spinal cord stimulators, and deep brain stimulation implanted with pulse generators should be used with caution;
• People at higher risk of noisy hearing loss and patients with hypoacusis symptoms should be used with caution;
• Pregnancy;
• Severe or recent heart disease;
• Personal history of epilepsy, use of known drugs that lower the seizure threshold, and other factors that may lower the seizure threshold (e.g., lack of sleep, infection, and alcohol abuse);
• Increased intracranial pressure;
• Acute phase of intracranial infection and hemorrhagic disease;
• Contraindications to MRI examination or claustrophobia;
• Refusal to sign informed consent.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham group	Sham	Intervention Name and Specification: Placebo coil (Magstim Company, Whitland, UK): looks and sounds consistent with true coil but does not produce current stimulation.
rTMS group	Repetitive transcranial magnetic stimulation	1. 5Hz-rTMS group 2. 10Hz-rTMS group 3. 30Hz-rTMS group Intervention Name and Specification: 1. Transcranial magnetic stimulator (M-100 Ultimate, Yingzhi Technology Co., Ltd., China) 2. 70 mm diameter figure-of-eight coil (BY90A, Yingzhi Technology Co., Ltd., China). Each group received acute and chronic stimulation, respectively. In the acute stimulation stage, patients only needed to do rTMS once, and HREM and HRV were administered before and after rTMS; in the chronic stimulation stage, patients received 25 minutes of rTMS true stimulation each time a day for 20 times, which was completed within 30 days, and the true stimulation parameters were the same as those of acute stimulation.

Primary Outcome Measures

Name	Time	Method
Real-time esophageal barium meal examination	Measured immediately after intervention.	The severity of the patient 's condition and the therapeutic effect were evaluated by defining the height and maximum width of the residual barium area.
High-resolution esophageal manometry（HREM）	Measured immediately after intervention.	HREM is the gold standard for the diagnosis of achalasia of cardia (AC), which can assess the relaxation ability of the lower esophageal sphincter (LES) and the contraction ability of the esophageal body. HREM dynamically collects the mean pressure data of multiple parts of the whole esophagus in real time, and converts the linear manometry pattern into color pressure topography. The basic manometry parameters include integrated relaxation pressure (IRP) and lower esophageal sphincter pressure (LESP), which can more truly reflect the relaxation function of the gastroesophageal junction (EGJ) and are the key indicators for the diagnosis of AC.
Eckardt score	Measured immediately after intervention.	The Eckardt scoring system is used to assess the severity of symptoms, with 0 to 1 in grade 0, 2 to 3 in grade I., 4 to 6 in grade II., and \> 6 in grade III. The more severe the symptoms, the higher the score, and can also be used for efficacy assessment.

Secondary Outcome Measures

Name	Time	Method
Heart rate variability assessment	Measured immediately after intervention.	Dynamic electrocardiogram recording analysis of sympathetic vagal activity.
Neurotransmitter detection analysis	Measured immediately after intervention.	Serum ACh, NO and VIP

Trial Locations

Locations (1)

Nanjing Drum Tower Hospital; 🇨🇳 Nanjing, China