Pharmacological Treatment on the Recovery of Neurosensory Disturbance After Bilateral Sagittal Split Osteotomy

Study Overview
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Brief Summary
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The bilateral sagittal split osteotomy (BSSO) of the mandible is one of the most used surgical techniques to achieve a harmonious jaw relation in the context of orthognathic surgery. Nevertheless, one of its main complications is neurosensory damage to the inferior alveolar nerve, which can cause severe impact in the quality of life on patients who suffer from it permanently. The purpose of this randomized clinical trial is to provide rigorous scientific evidence of the pharmacological effect of 1) Melatonin, 2) combination uridine triphosphate (UTP), cytidine monophosphate (CMP), and hydroxycobalamin (UTP/CMP/hydroxycobalamin) and 3) hydroxycobalamin regarding neurosensory disturbances incidence and persistence after BSSO.

Detailed Description
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The study will be done according to the international standards of the Helsinki convention for medical research and approved by the scientific ethics committee of Universidad de los Andes Clinic. All subjects will give their signed consent to participate of this clinical research. This clinical randomized trial will be double-blinded as both the patient and the surgeon will not know the treatment used until the experiment is over. The randomization will be done using random.org software to assign participants into 4 groups. Groups A, B and C will receive the medication, whereas the Group P will receive a placebo.

Official Title
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Pharmacological Treatment on the Recovery of Neurosensory Disturbance After Bilateral Sagittal Split Osteotomy: a Randomized, Double-blind Trial

Conditions
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Retrognathism, Prognathism, Orthognathic Surgery, Neurosensory Disorder

Intervention / Treatment
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* Procedure: Orthognathic Surgery
* Drug: Melatonin 10 MG Oral Tablet
* Drug: Hydroxycobalamin
* Drug: Centrum


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with dentomaxillofacial anomalies who present a complete mandibular dental arch and who have not undergone previous mandibular surgery. Exclusion Criteria: patients who: do not have sufficient information in their clinical records cannot be contacted do not attend their check-ups (for at least 24 postoperative months in cases with DNS) have refused consent to the use of their information for purposes of research. already undergoing Orthognathic Surgery with systemic conditions prone to alter recovery patterns or serious systemic diseases (decompensated metabolic disorders; neoplasms; osteodysplasias; neuropathies). pregnancy

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The participants will be assigned into 4 groups. Groups A, B and C will receive the medication (Melatonin, Hydroxycobalamin and combination UTP/CMP/hydroxycobalamin), whereas the Group P will receive placebo.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Citoneurone<br>Groups A will receive the pharmacology treatment with 1.5 mg uridine triphosphate, 2.5 mg cytidine monophosphate and 1 mg hydroxycobalamin (Citoneurone). One capsule orally three times a day for 60 days as suggested by the manufacturer for patients with trauma - compressive peripheral neural disorders. | Procedure: Orthognathic Surgery<br>* Prognathism/Retrognathism correction through surgical procedures<br>* Other names: Bilateral Sagittal Split Osteotomy;Drug: Centrum<br>* Groups A will receive the pharmacology treatment with 1.5 mg uridine triphosphate, 2.5 mg cytidine monophosphate and 1 mg hydroxycobalamin (Citoneuron). One capsule orally three times a day for 60 days as suggested by the manufacturer for patients with trauma - compressive peripheral neural disorders.<br>* Other names: Citoneurone [Cytidine + Hydroxocobalamin, + Uridine];|
| Experimental: Melatonin<br>Group B will receive the pharmacology treatment with 10 mg Melatonin. One capsule orally at night for 60 days. | Procedure: Orthognathic Surgery<br>* Prognathism/Retrognathism correction through surgical procedures<br>* Other names: Bilateral Sagittal Split Osteotomy;Drug: Melatonin 10 MG Oral Tablet<br>* Group B will receive the pharmacology treatment with 10 mg Melatonin. One capsule orally at night for 60 days.<br>|
| Experimental: Hydroxycobalamin<br>Group C will receive the pharmacology treatment with 1 mg hydroxycobalamin (vitamin B12). One capsule daily for 60 days. | Procedure: Orthognathic Surgery<br>* Prognathism/Retrognathism correction through surgical procedures<br>* Other names: Bilateral Sagittal Split Osteotomy;Drug: Hydroxycobalamin<br>* Group C will receive the pharmacology treatment with 1 mg hydroxycobalamin (vitamin B12). One capsule daily for 60 days.<br>|
| Placebo Comparator: Placebo<br>The controls will receive 1 capsule placebo containing 5 mg starch to be taken once daily. | Procedure: Orthognathic Surgery<br>* Prognathism/Retrognathism correction through surgical procedures<br>* Other names: Bilateral Sagittal Split Osteotomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurosensory Activity | Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others | pre-operative | 
| Neurosensory Activity | Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others | 1 day postoperative | 
| Neurosensory Activity | Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others | 3 day postoperative | 
| Neurosensory Activity | Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others | 2 weeks postoperative. | 
| Neurosensory Activity | Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others | 1 month postoperative | 
| Neurosensory Activity | Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others | 2 month postoperative | 
| Neurosensory Activity | Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others | 6 month postoperative | 
| Neurosensory Activity | Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others | 12 month postoperative | 
| Neurosensory Activity | Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others | 18 month postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Test | Subjective testing using a questionnaire and visual analogue scale. 0 = normal sensation, 10= more severe sensory deficit. | pre-operative, at day 1 and 3, at week 2, and at month 1, 2, 6, 12 and 18 after surgery. | 
| Objetive Test | The Semmes-Weinstein (SW) test of sensitivity to touch/pressure will be used. | pre-operative, at day 1 and 3, at week 2, and at month 1, 2, 6, 12 and 18 after surgery. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bilateral Sagittal Split Osteotomy, Neurosensory Disturbances