Vitamin B Complex for Inferior Alveolar Nerve Paresthesia Recovery

Detailed Description

Study Design Overview

This is a single-center, parallel-group, superiority, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy of vitamin B complex supplementation in promoting sensory recovery among patients with paresthesia of the inferior alveolar nerve (IAN) following mandibular third molar extraction. The study adopts an experimental, longitudinal design with repeated measures at six time points over an eight-week follow-up period.

The trial will be conducted at the Faculdade de Odontologia da Universidade de São Paulo (FOUSP) and at the Fundação para o Desenvolvimento da Odontologia (FUNDECTO), both located in São Paulo, Brazil. Enrollment is expected to occur consecutively based on patient referrals and spontaneous demand from the dental surgery outpatient clinics. The total planned sample size is 50 participants, determined dynamically based on clinical availability but powered to detect clinically meaningful differences between groups based on prior literature.

Study Setting and Recruitment

Potential participants will be identified among patients presenting to the oral and maxillofacial surgery clinics at FOUSP/FUNDECTO with chief complaints of persistent altered sensation in the distribution of the inferior alveolar nerve following recent mandibular third molar extraction. Recruitment will be performed by trained research assistants who will screen all postoperative patients meeting the temporal inclusion window (symptom onset between 7 and 30 days prior to screening). Eligible patients will be approached, provided with a detailed explanation of the study, and given the Informed Consent Form (ICF). A minimum of 24 hours will be allowed for consideration before obtaining written informed consent.

To maximize recruitment and retention, patients will receive reminder calls or text messages before each scheduled visit. Transportation reimbursement will not be provided as all visits coincide with routine postoperative follow-up appointments already scheduled as part of standard care at the institution.

Randomization and Allocation Concealment

After providing informed consent and completing baseline assessments (T0), eligible participants will be randomly assigned in a 1:1 ratio to either the vitamin B complex group or the placebo group. Randomization will be performed using a computer-generated random sequence with variable block sizes (block sizes 2, 4, or 6, randomly selected) to ensure allocation concealment and balance between groups over time. The randomization list will be generated by an independent statistician who will have no direct contact with participants or outcome assessors.

Allocation concealment will be maintained using sequentially numbered, opaque, sealed envelopes. The envelopes will be prepared and kept by a designated researcher (the "pharmacy custodian") who is not involved in participant screening, enrollment, outcome assessments, or data analysis. After baseline assessments are completed and eligibility is reconfirmed, the enrolling investigator will contact the pharmacy custodian, who will open the next envelope and dispense the corresponding medication kit to the participant.

Blinding

This study employs double-blinding. The following individuals will remain blinded to group allocation until database lock:

* Participants * Outcome assessors (clinicians performing sensory tests) * Primary investigator (during data collection phase) * Statistician (during interim blinded sample size re-estimation and final analysis, until database lock)

Only the pharmacy custodian will be unblinded to group assignment. The custodian is responsible for preparing, storing, and dispensing the coded medication kits. To maintain blinding, the vitamin B complex and placebo capsules are identical in appearance (size, color, shape, and opaque capsule shell). Both are packaged in identical white plastic bottles labeled only with a unique participant identification number, dosage instructions ("Take one capsule daily by mouth"), and storage conditions. No other identifying information appears on the bottles.

In case of a medical emergency where knowledge of the treatment assignment is required for patient safety, an emergency unblinding procedure will be available through the pharmacy custodian, who can be contacted 24/7. Any unblinding event will be documented in the participant's case report form (CRF) and reported to the ethics committee.

Intervention Groups

Group 1 - Vitamin B Complex (Active Intervention):

Participants receive one capsule daily for eight weeks (56 days). Each capsule contains the following formulation:

* Thiamine (thiamine mononitrate) - 10 mg * Riboflavin - 10 mcg * Niacin (91% niacinamide, 9% niacin) - 100 mg * Pyridoxine (pyridoxine HCl) - 10 mg * Folate (folic acid) - 400 mcg * Cyanocobalamin (vitamin B12) - 12 mcg * Biotin (as d-biotin) - 45 mcg * Pantothenic acid (calcium pantothenate) - 20 mg

These doses are within the standard therapeutic range for neuropathy indications and are considered safe for daily use over eight weeks. Participants are instructed to take the capsule with food to minimize gastrointestinal discomfort.

Group 2 - Placebo (Control Intervention):

Participants receive one capsule daily for eight weeks. The placebo capsule is identical in appearance to the active capsule and contains only the pharmaceutical vehicle (microcrystalline cellulose or similar inert excipient) with no active vitamins.

Medication Supply and Adherence Monitoring

All study medications will be produced in compliance with good manufacturing practices. The vitamin B complex and placebo capsules will be packaged in kits containing a 56-day supply (56 capsules per participant). At the baseline visit (T0), participants receive their assigned medication kit after randomization. They are instructed to take one capsule daily at approximately the same time each day, preferably with a meal.

Adherence will be monitored through three strategies:

1. Capsule count: At each follow-up visit (T1, T2, T3, T4, T5), participants return their medication bottle. The pharmacy custodian counts remaining capsules and records the count in the CRF. Adherence is calculated as (capsules dispensed - capsules returned) / expected capsules taken over the period. Adherence ≥80% is considered acceptable. 2. Self-report diary: Participants receive a simple daily checklist to record capsule intake. Diaries are collected at each visit. 3. Direct questioning: At each visit, participants are asked about any missed doses and reasons for non-adherence.

Participants with adherence below 80% will be counseled. Those who persistently miss doses (adherence \<60% over two consecutive intervals) may be withdrawn from the study but will still be included in the intention-to-treat analysis.

Prohibited Concomitant Medications and Washout

Participants must refrain from using any additional vitamin B complex supplements or any other neurotropic agents (e.g., methylcobalamin, alpha-lipoic acid, acetyl-L-carnitine, pregabalin, gabapentin) during the study period. Stable use (≥30 days prior to enrollment) of medications that may affect sensory function (e.g., antidepressants, anticonvulsants) is permitted provided the dose remains unchanged throughout the study. Any change in such medications will be recorded as a protocol deviation.

A formal washout period is not required in this parallel-group design because each participant receives only one intervention. The low half-life of B vitamins (approximately 2-6 hours for pyridoxine, 6 days for cyanocobalamin in liver storage) does not create carryover effects that would warrant washout. Participants who have taken vitamin B complex supplements within 30 days prior to screening are excluded to prevent baseline bias.

Study Procedures and Visit Schedule

Participants attend six scheduled visits over 56 days:

T0 - Baseline (Day 0):

* Informed consent reconfirmation * Demographics and medical/dental history * Review inclusion/exclusion criteria * Baseline sensory assessment battery (detailed below) * Randomization and dispensing of medication kit (56 capsules) * Instruction on capsule intake and diary completion * Scheduling of follow-up visits

T1 - Week 1 (Day 7 ± 2 days):

* Medication adherence assessment (capsule count and diary) * Adverse event inquiry * Brief sensory assessment (VAS, Von Frey monofilament test) * Dispensing of remaining medication (if needed - no new supply; participants continue with original kit)

T2 - Week 2 (Day 14 ± 2 days):

* Complete sensory assessment battery * Medication adherence assessment * Adverse event inquiry * Diary collection and review

T3 - Week 4 (Day 28 ± 3 days):

* Complete sensory assessment battery * Medication adherence assessment * Adverse event inquiry * Diary review