Patients Undergoing Open Thyroid Surgery
Conditions
Keywords
thyroid surgery, recurrent laryngeal nerve, mecobalamin
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.
Detailed description
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.
Interventions
DRUGMecobalamin
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.
DRUGplacebo
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.
Sponsors
West China Tianfu Hospital, Sichuan University
Shang Jin Hospital of West China Hospital,Sichuan University
Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China
Sanya People's Hospital
West China Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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.
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Jitter | Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative | 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. |
| Shimmer | Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative | 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. |
| Fundamental frequency (F0) | Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative | — |
| Maximum Phonational Frequency Range (MPFR) | Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative | The frequency range from the lowest to the highest pitch a person can produce (in Hz or semitones). |
| Noise-to-Harmonic Ratio (NHR) | Preoperative, within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Eating Assessment Tool (EAT-10) | Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative | This instrument consists of 10 questions, with severity rated on a scale from 0 to 4. A score of 0 indicates no problem, 1 indicates mild, 2 indicates moderate, 3 indicates severe, and 4 indicates very severe. A total score above 3 is generally considered indicative of abnormal swallowing function. |
| The Voice Handicap Index-10 (VHI-10) | Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative | The VHI-10 is a voice disorder index scale containing 10 items, comprising 5 functional items, 3 physical items, and 2 emotional items. Each item is scored from 0 to 4, with different scores representing the frequency of occurrence for that item: Never is 0 points; Almost Never is 1 point; Sometimes is 2 points; Almost Always is 3 points; and Always is 4 points. A higher score indicates a greater impact of the voice disorder in that domain and a more severe self-assessment of the voice disorder by the subject. The critical value for the VHI-10 is 8 points, and subjects with a VHI score ≥ 8 are classified as having a voice disorder. |
| Adverse Events | Within two weeks after surgery, 1 month postoperative, 3 months postoperative, and 6 months postoperative | At each follow-up visit, adverse events (including adverse drug reactions) were recorded through patient interviews and physical examinations. |
| The Voice-Related Quality of Life (V-RQOL-10) scale | Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative | Consists of 10 items, encompassing two domains: social-emotional and physical-functioning. The items describe the subjective experiences of patients with voice disorders. Severity is rated on a 5-point scale, where 1 represents none, 2 represents a little, 3 represents a moderate amount, 4 represents a lot, and 5 represents a great deal. This questionnaire uses reverse scoring, and the final scores need to be transformed to a 0 to 100 scale. A higher overall score indicates better voice-related quality of life, while a lower score indicates worse voice-related quality of life. |
| The subjective auditory-perceptual assessment of voice quality (GRBAS Scale) | Preoperative, 1 day postoperative, 1 month postoperative, 3 months postoperative, and 6 months postoperative | This scale consists of five parameters: overall grade of hoarseness (G), roughness (R), breathiness (B), asthenia (A), and strain (S). Each parameter is rated on a severity scale from 0 to 3: 0 indicates normal, 1 indicates mild deviation, 2 indicates moderate deviation, and 3 indicates severe deviation. A higher score represents a more severe voice disorder. The assessment is conducted by professional audiologists, voice specialists, and the patient's family members. |
| Stroboscopy | Preoperative, If necessary after surgery | This examination utilizes the principle of persistence of vision to observe the vocal cords in a seemingly stationary or slow-motion vibrating state through visual superposition. Dynamic laryngoscopy is performed preoperatively, and the stroboscopic findings are recorded. Postoperatively, it is conducted on patients presenting with voice abnormalities, dysphonia, or suspected abnormal vocal cord mobility to confirm the mobility of the vocal cords. |
| Intraoperative neural signals | Intraoperative | During the surgery, IONM technology was used to monitor neural signals from the vagus nerve, recurrent laryngeal nerve, and superior laryngeal nerve both before and after nerve exposure. |
Countries
China
Contacts
Primary ContactJianyong Lei
Backup ContactYu Feng
Outcome results
None listed