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

NCT05536596 | Unknown Phase 2

• 1 other identifier: PISV01
• Study Type: interventional
• Target: 220
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Retrognathism; Prognathism; Orthognathic Surgery; Neurosensory Disorder

Keywords

Bilateral Sagittal Split Osteotomy; Neurosensory Disturbances

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (2)

• Subjective Test

  pre-operative, at day 1 and 3, at week 2, and at month 1, 2, 6, 12 and 18 after surgery.

• Objetive Test

  pre-operative, at day 1 and 3, at week 2, and at month 1, 2, 6, 12 and 18 after surgery.

Study Arms (4)

Citoneurone

EXPERIMENTAL

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; Drug: Centrum

Melatonin

EXPERIMENTAL

Group B will receive the pharmacology treatment with 10 mg Melatonin. One capsule orally at night for 60 days.

Procedure: Orthognathic Surgery; Drug: Melatonin 10 MG Oral Tablet

Hydroxycobalamin

EXPERIMENTAL

Group C will receive the pharmacology treatment with 1 mg hydroxycobalamin (vitamin B12). One capsule daily for 60 days.

Procedure: Orthognathic Surgery; Drug: Hydroxycobalamin

Placebo

PLACEBO COMPARATOR

The controls will receive 1 capsule placebo containing 5 mg starch to be taken once daily.

Procedure: Orthognathic Surgery

Interventions

Orthognathic Surgery PROCEDURE

Prognathism/Retrognathism correction through surgical procedures

Also known as: Bilateral Sagittal Split Osteotomy

Citoneurone; Hydroxycobalamin; Melatonin; Placebo

Melatonin 10 MG Oral Tablet DRUG

Group B will receive the pharmacology treatment with 10 mg Melatonin. One capsule orally at night for 60 days.

Melatonin

Hydroxycobalamin DRUG

Group C will receive the pharmacology treatment with 1 mg hydroxycobalamin (vitamin B12). One capsule daily for 60 days.

Hydroxycobalamin

Centrum DRUG

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.

Also known as: Citoneurone [Cytidine + Hydroxocobalamin, + Uridine]

Citoneurone

Eligibility Criteria

• Age: 13 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitat Internacional de Catalunya: lead
• Universidad de los Andes, Chile: collaborator

Related Publications (10)

• Alolayan AB, Leung YY. Resolution of neurosensory deficit after mandibular orthognathic surgery: A prospective longitudinal study. J Craniomaxillofac Surg. 2017 May;45(5):755-761. doi: 10.1016/j.jcms.2017.01.032. Epub 2017 Feb 12.

  PMID: 28318920 BACKGROUND

• Teerijoki-Oksa T, Jaaskelainen SK, Forssell K, Forssell H, Vahatalo K, Tammisalo T, Virtanen A. Risk factors of nerve injury during mandibular sagittal split osteotomy. Int J Oral Maxillofac Surg. 2002 Feb;31(1):33-9. doi: 10.1054/ijom.2001.0157.

  PMID: 11936397 BACKGROUND

• da Costa Senior O, Gemels B, Van der Cruyssen F, Agbaje JO, De Temmerman G, Shaheen E, Lambrichts I, Politis C. Long-term neurosensory disturbances after modified sagittal split osteotomy. Br J Oral Maxillofac Surg. 2020 Oct;58(8):986-991. doi: 10.1016/j.bjoms.2020.05.010. Epub 2020 Jul 4.

  PMID: 32631751 BACKGROUND

• Seddon HJ. A Classification of Nerve Injuries. Br Med J. 1942 Aug 29;2(4260):237-9. doi: 10.1136/bmj.2.4260.237. No abstract available.

  PMID: 20784403 BACKGROUND

• Schlund M, Grall P, Ferri J, Nicot R. Effect of modified bilateral sagittal split osteotomy on inferior alveolar nerve neurosensory disturbance. Br J Oral Maxillofac Surg. 2022 Oct;60(8):1086-1091. doi: 10.1016/j.bjoms.2022.04.001. Epub 2022 Apr 13.

  PMID: 35606209 BACKGROUND

• Ylikontiola L, Kinnunen J, Oikarinen K. Factors affecting neurosensory disturbance after mandibular bilateral sagittal split osteotomy. J Oral Maxillofac Surg. 2000 Nov;58(11):1234-9; discussion 1239-40. doi: 10.1053/joms.2000.16621.

  PMID: 11078134 BACKGROUND

• Yoshioka I, Tanaka T, Khanal A, Habu M, Kito S, Kodama M, Oda M, Wakasugi-Sato N, Matsumoto-Takeda S, Seta Y, Tominaga K, Sakoda S, Morimoto Y. Correlation of mandibular bone quality with neurosensory disturbance after sagittal split ramus osteotomy. Br J Oral Maxillofac Surg. 2011 Oct;49(7):552-6. doi: 10.1016/j.bjoms.2010.09.014. Epub 2010 Nov 10.

  PMID: 21071118 BACKGROUND

• van Merkesteyn JP, Zweers A, Corputty JE. Neurosensory disturbances one year after bilateral sagittal split mandibular ramus osteotomy performed with separators. J Craniomaxillofac Surg. 2007 Jun-Jul;35(4-5):222-6. doi: 10.1016/j.jcms.2007.04.006. Epub 2007 Jul 30.

  PMID: 17681774 BACKGROUND

• Colella G, Cannavale R, Vicidomini A, Lanza A. Neurosensory disturbance of the inferior alveolar nerve after bilateral sagittal split osteotomy: a systematic review. J Oral Maxillofac Surg. 2007 Sep;65(9):1707-15. doi: 10.1016/j.joms.2007.05.009.

  PMID: 17719387 BACKGROUND

• Panula K, Finne K, Oikarinen K. Neurosensory deficits after bilateral sagittal split ramus osteotomy of the mandible--influence of soft tissue handling medial to the ascending ramus. Int J Oral Maxillofac Surg. 2004 Sep;33(6):543-8. doi: 10.1016/j.ijom.2003.11.005.

  PMID: 15308252 BACKGROUND

MeSH Terms

Conditions

Retrognathia; Prognathism; Sensation Disorders

Interventions

Orthognathic Surgery; Melatonin; Tablets; Hydroxocobalamin; Cytidine; Uridine

Condition Hierarchy (Ancestors)

Jaw Abnormalities; Jaw Diseases; Musculoskeletal Diseases; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Stomatognathic Diseases; Mandibular Diseases; Stomatognathic System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Surgery, Oral; Dentistry; Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dosage Forms; Pharmaceutical Preparations; Vitamin B 12; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Pedro Sole, DMD, OMFS

  Universidad de Los Andes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pedro Sole, DMD, OMFS

CONTACT

+56 9 9235 2728; psole@uic.es

Maximiliano Bravo, DMD

CONTACT

+56 9 7690 0878; mabravo9@uc.cl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: In order to maintain the blindness of subjects and the main surgeon, the drugs will be delivered in an identical brown non-translucent bag. The only one who will know about the assignament will be the second researcher.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Surgeon

Model Details: 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.

Study Record Dates

• First Submitted: September 1, 2022
• First Posted: September 13, 2022
• Study Start: September 30, 2022
• Primary Completion: June 30, 2024
• Study Completion: December 31, 2024
• Last Updated: September 13, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share