Mecobalamin in Promoting Recurrent Laryngeal Nerve Function Recovery After Thyroid Surgery

NCT07274696 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: 2025(2153)
• Study Type: interventional
• Target: 528
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Patients Undergoing Open Thyroid Surgery

Keywords

thyroid surgery; recurrent laryngeal nerve; mecobalamin

Outcome Measures

Primary Outcomes (5)

• Jitter

  Jitter reflects the regularity of the voice in terms of frequency. A smaller jitter value indicates higher regularity of the voice in terms of frequency.

  Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative

• Shimmer

  Shimmer reflects the regularity of the voice in terms of amplitude. A smaller shimmer value indicates higher regularity of the voice in terms of amplitude.

  Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative

• Fundamental frequency (F0)

  Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative

• Maximum Phonational Frequency Range (MPFR)

  The frequency range from the lowest to the highest pitch a person can produce (in Hz or semitones).

  Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative

• Noise-to-Harmonic Ratio (NHR)

  The NHR parameter is the ratio of non-harmonic components within the 1,500-4,500 Hz range to harmonic components within the 70-4,500 Hz range. It can be used to assess the proportion of noise components in the voice.

  Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative

Secondary Outcomes (7)

• The Voice Handicap Index-10 (VHI-10)

  Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative

• The Voice-Related Quality of Life (V-RQOL-10) scale

  Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative

• The subjective auditory-perceptual assessment of voice quality (GRBAS Scale)

  Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative

• Stroboscopy

  Preoperative, If necessary after surgery

• Intraoperative neural signals

  Intraoperative

Study Arms (2)

Mecobalamin Group

EXPERIMENTAL

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.

Drug: Mecobalamin

Control group

PLACEBO COMPARATOR

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.

Drug: placebo

Interventions

Mecobalamin DRUG

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.

Mecobalamin Group

placebo DRUG

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.

Control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Shang Jin Hospital of West China Hospital,Sichuan University: collaborator
• Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China: collaborator
• Sanya People's Hospital: collaborator
• West China Hospital: lead
• West China Tianfu Hospital, Sichuan University: collaborator

Study Sites (1)

West China hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (6)

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

• 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 RESULT

MeSH Terms

Interventions

mecobalamin

Central Study Contacts

Jianyong Lei

CONTACT

+86 19983137992; leijianyong@scu.edu.cn

Yu Feng

CONTACT

+86 15183042703; 1350502131@qq.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: West China Hospital, Sichuan University

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: December 10, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 10, 2025

Record last verified: 2025-12

Locations

CN (1)