Mecobalamin in Promoting Recurrent Laryngeal Nerve Function Recovery After Thyroid Surgery

Официальное название

A Multicenter, Open-Label, Randomized, Placebo-Controlled Study Protocol on the Effect of Mecobalamin in Promoting Recurrent Laryngeal Nerve Function Recovery After Thyroid Surgery（MIREN Trial）

Обзор

Recurrent laryngeal nerve injury is one of the most common and serious complications affecting quality of life after thyroid surgery. Intraoperative traction, clamping, thermal injury, or direct transection can lead to its dysfunction. Unilateral injury causes vocal cord paralysis, manifesting as hoarseness, coughing while drinking, and vocal fatigue; bilateral injury can result in severe dyspnea, potentially requiring tracheotomy and posing life-threatening risks. Although intraoperative neuromonitoring has reduced the risk of permanent injury, temporary nerve palsy remains very common, imposing a dual physiological and psychological burden on patients. Therefore, exploring safe and effective methods to promote the recovery of recurrent laryngeal nerve function postoperatively is an urgent clinical issue in thyroid surgery. As a motor nerve, the functional recovery of the recurrent laryngeal nerve depends on axonal regeneration and reinnervation of the laryngeal muscles. This process is slow and often incomplete, influenced by factors such as the extent of injury and patient age. Current clinical management of postoperative recurrent laryngeal nerve palsy primarily involves conservative observation and voice training, lacking proactive pharmacological interventions. This presents a clear rationale and clinical entry point for research. Mecobalamin, the active form of vitamin B12, has high bioavailability and directly participates in methylation reactions, as well as nucleic acid and protein synthesis. Studies have confirmed its multifaceted role in treating peripheral neuropathy: (1) It promotes myelin regeneration by enhancing Erk1/2 and Akt activity, accelerating the myelination of damaged nerve fibers; (2) It enhances nerve regeneration by promoting the synthesis and secretion of nerve growth factors; (3) It improves nerve cell metabolism and repairs damaged nerve cell membranes; (4) It exerts neurotrophic effects by stimulating the proliferation and activity of Schwann cells, thereby increasing the secretion of neurotrophic factors and optimizing the microenvironment for nerve regeneration. Although mecobalamin is theoretically beneficial for nerve repair and has been successfully applied in other neuropathies, high-quality clinical studies specifically targeting its use for recurrent laryngeal nerve recovery after thyroid surgery are still lacking. Existing literature consists mostly of small-sample retrospective analyses or case reports with inconsistent conclusions and limitations such as selection bias and inadequate control of confounding factors. There is a lack of large-sample, multicenter, randomized controlled trials to provide high-level evidence-based medical data. Based on this background, the investigators plan to conduct a nationwide multicenter, randomized controlled study. The primary endpoint will be objective acoustic parameters measured by computerized voice analysis, while secondary endpoints will include patient-reported quality of life outcomes, time to voice recovery, subjective patient satisfaction, incidence of permanent paralysis, and adverse drug reactions. The study aims to scientifically and objectively evaluate the efficacy and safety of mecobalamin in promoting the recovery of recurrent laryngeal nerve function after thyroid cancer surgery, providing new therapeutic strategies to optimize perioperative management and improve the quality of life for patients.

Подробное описание

This study is a multicenter, open-label, randomized controlled trial. Inclusion Criteria: (1) Patients aged 18-75 years (inclusive); (2) Scheduled to undergo thyroid surgery (including thyroid gland and isthmus resection, total thyroidectomy, etc.); (3) Preoperative laryngoscopy confirms normal bilateral vocal cord mobility; (4) Intraoperative neuromonitoring (IONM) technology is used in all cases; (5) Voluntarily and capable of providing signed informed consent. Exclusion Criteria: (1) Pre-existing hoarseness or recurrent laryngeal nerve palsy; (2) Planned surgery limited to the thyroid isthmus only, or the isthmus plus the medial one-third of both lobes; (3) Pre-existing severe peripheral neuropathy due to other causes (e.g., diabetes mellitus, alcoholism); (4) Pregnant or lactating women; (5) Chronic use of high-dose vitamin B12 or other neurotrophic drugs; (6) Conditions interfering with drug administration or absorption (e.g., dysphagia, intestinal obstruction); (7) Severe pre-existing comorbidities with intolerance to general anesthesia or surgery; (8) History of vitamin B12 allergy; (9) Concurrent participation in another clinical study that may interfere with this trial.

Eligible patients will be randomly assigned in a 1:1 ratio to either the experimental group (Mecobalamin group) or the control group (control group). Data to be collected includes: (1) Basic Information: Name, randomization number, treating hospital, hospital admission number, group assignment, phone number, age, height, weight, BMI, comorbidities (cardiovascular, endocrine, thyroid diseases, etc.); (2) Preoperative Imaging and Laboratory Data: Laryngoscopy results, thyroid ultrasound, electrocardiogram (ECG), TSH, FT3, FT4, TT3, TT4, Tg, TgAb; (3) Surgical Data: Diagnosis, operating surgeon, surgical procedure, surgery date, intraoperative complications, intraoperative signal changes of the vagus nerve, recurrent laryngeal nerve, and superior laryngeal nerve; (4) Voice Assessments (Preoperative, Postoperative Day 1, Postoperative 1 month, 3 months, 6 months): Objective acoustic parameters of voice quality, Voice Handicap Index-10 (VHI-10), Voice-Related Quality of Life-10 (V-RQOL-10), subjective perceptual evaluation of voice quality (GRBAS scale); (5) Postoperative Pathological Results: Postoperative pathological TNM staging, postoperative pathological diagnosis, postoperative treatment; (6) Surgical Complications: Whether secondary surgery was required due to complications; (7) Postoperative Mecobalamin/Placebo Usage: Dosage, course duration, adverse drug events.

Вмешательства

• Препарат Mecobalamin
  The patient began taking mecobalamin tablets orally within 24 hours after thyroid surgery, three times a day, 0.5mg each time, for three consecutive months.
• Препарат placebo
  The patient was given a placebo within 24 hours after thyroid surgery, which was identical in appearance, size, color, dosage form, weight, taste, and smell to mecobalamin tablets, three times a day, 0.5mg each time, for three consecutive months.

Первичные конечные точки

• Jitter [Срок оценки: Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative]
• Shimmer [Срок оценки: Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative]
• Fundamental frequency (F0) [Срок оценки: Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative]
• Maximum Phonational Frequency Range (MPFR) [Срок оценки: Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative]
• Noise-to-Harmonic Ratio (NHR) [Срок оценки: Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative]

Вторичные конечные точки (7)

• The Voice Handicap Index-10 (VHI-10) [Срок оценки: Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative]
• The Voice-Related Quality of Life (V-RQOL-10) scale [Срок оценки: Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative]
• The subjective auditory-perceptual assessment of voice quality (GRBAS Scale) [Срок оценки: Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative]
• Stroboscopy [Срок оценки: Preoperative, If necessary after surgery]
• Intraoperative neural signals [Срок оценки: Intraoperative]
• The Eating Assessment Tool (EAT-10) [Срок оценки: Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative]
• Adverse Events [Срок оценки: Within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative]

Критерии участия

Критерии включения

Patients aged 18-75 years (inclusive) Scheduled to undergo thyroid surgery (including thyroid gland and isthmus resection, total thyroidectomy, etc.) Preoperative laryngoscopy confirms normal bilateral vocal cord mobility Intraoperative neuromonitoring (IONM) technology is used in all cases Voluntarily and capable of providing signed informed consent.

Критерии исключения

Pre-existing hoarseness or recurrent laryngeal nerve palsy Planned surgery limited to the thyroid isthmus only, or the isthmus plus the medial one-third of both lobes Pre-existing severe peripheral neuropathy due to other causes (e.g., diabetes mellitus, alcoholism) Pregnant or lactating women Chronic use of high-dose vitamin B12 or other neurotrophic drugs Conditions interfering with drug administration or absorption (e.g., dysphagia, intestinal obstruction) Severe pre-existing comorbidities with intolerance to general anesthesia or surgery History of vitamin B12 allergy Concurrent participation in another clinical study that may interfere with this trial

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• West China hospital of Sichuan University — Чэнду

Публикации

• Stojadinovic A, Shaha AR, Orlikoff RF, Nissan A, Kornak MF, Singh B, Boyle JO, Shah JP, Brennan MF, Kraus DH. Prospective functional voice assessment in patients undergoing thyroid surgery. Ann Surg. 2002 Dec;236(6):823-32. doi: 10.1097/00000658-200212000-00015. PMID 12454521
• Xia Y, Zhu Y, Ling L, Xu F, Yang Y, Ye J, Tan W, Chen Z, Liu Q, Wei W, Zhang J, Zhang A, Zhang L, Song E, Gong C. Effect of methylcobalamin on capecitabine induced hand-foot syndrome in patients with HER2 negative early breast cancer: multicentre, double blind, randomised, placebo controlled, phase 3 trial. BMJ. 2025 Sep 11;390:e084290. doi: 10.1136/bmj-2025-084290. PMID 40935571
• Nishimoto S, Tanaka H, Okamoto M, Okada K, Murase T, Yoshikawa H. Methylcobalamin promotes the differentiation of Schwann cells and remyelination in lysophosphatidylcholine-induced demyelination of the rat sciatic nerve. Front Cell Neurosci. 2015 Aug 4;9:298. doi: 10.3389/fncel.2015.00298. eCollection 2015. PMID 26300733
• Kim HA, Mindos T, Parkinson DB. Plastic fantastic: Schwann cells and repair of the peripheral nervous system. Stem Cells Transl Med. 2013 Aug;2(8):553-7. doi: 10.5966/sctm.2013-0011. Epub 2013 Jul 1. PMID 23817134
• Stoll G, Muller HW. Nerve injury, axonal degeneration and neural regeneration: basic insights. Brain Pathol. 1999 Apr;9(2):313-25. doi: 10.1111/j.1750-3639.1999.tb00229.x. PMID 10219748
• Zhou T, Wang X, Zhang J, Zhou E, Xu C, Shen Y, Zou J, Lu W, Su K, Huang W, Yi H, Yin S. Global burden of thyroid cancer from 1990 to 2021: a systematic analysis from the Global Burden of Disease Study 2021. J Hematol Oncol. 2024 Aug 27;17(1):74. doi: 10.1186/s13045-024-01593-y. PMID 39192360

Идентификаторы

NCT: NCT07274696 · 2025(2153)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗