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

Primary Purpose

Retrognathism, Prognathism, Orthognathic Surgery

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Orthognathic Surgery
Melatonin 10 MG Oral Tablet
Hydroxycobalamin
Centrum
Sponsored by
Universitat Internacional de Catalunya
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Retrognathism focused on measuring Bilateral Sagittal Split Osteotomy, Neurosensory Disturbances

Eligibility Criteria

13 Years - 70 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Citoneurone

    Melatonin

    Hydroxycobalamin

    Placebo

    Arm Description

    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.

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

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

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

    Outcomes

    Primary Outcome Measures

    Neurosensory Activity
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Neurosensory Activity
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Neurosensory Activity
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Neurosensory Activity
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Neurosensory Activity
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Neurosensory Activity
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Neurosensory Activity
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Neurosensory Activity
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Neurosensory Activity
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others

    Secondary Outcome Measures

    Subjective Test
    Subjective testing using a questionnaire and visual analogue scale. 0 = normal sensation, 10= more severe sensory deficit.
    Objetive Test
    The Semmes-Weinstein (SW) test of sensitivity to touch/pressure will be used.

    Full Information

    First Posted
    September 1, 2022
    Last Updated
    September 8, 2022
    Sponsor
    Universitat Internacional de Catalunya
    Collaborators
    Universidad de los Andes, Chile
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05536596
    Brief Title
    Pharmacological Treatment on the Recovery of Neurosensory Disturbance After Bilateral Sagittal Split Osteotomy
    Official Title
    Pharmacological Treatment on the Recovery of Neurosensory Disturbance After Bilateral Sagittal Split Osteotomy: a Randomized, Double-blind Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 30, 2022 (Anticipated)
    Primary Completion Date
    June 30, 2024 (Anticipated)
    Study Completion Date
    December 31, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Universitat Internacional de Catalunya
    Collaborators
    Universidad de los Andes, Chile

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.
    Detailed Description
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Retrognathism, Prognathism, Orthognathic Surgery, Neurosensory Disorder
    Keywords
    Bilateral Sagittal Split Osteotomy, Neurosensory Disturbances

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    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
    ParticipantCare Provider
    Masking Description
    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.
    Allocation
    Randomized
    Enrollment
    220 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Citoneurone
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Melatonin
    Arm Type
    Experimental
    Arm Description
    Group B will receive the pharmacology treatment with 10 mg Melatonin. One capsule orally at night for 60 days.
    Arm Title
    Hydroxycobalamin
    Arm Type
    Experimental
    Arm Description
    Group C will receive the pharmacology treatment with 1 mg hydroxycobalamin (vitamin B12). One capsule daily for 60 days.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    The controls will receive 1 capsule placebo containing 5 mg starch to be taken once daily.
    Intervention Type
    Procedure
    Intervention Name(s)
    Orthognathic Surgery
    Other Intervention Name(s)
    Bilateral Sagittal Split Osteotomy
    Intervention Description
    Prognathism/Retrognathism correction through surgical procedures
    Intervention Type
    Drug
    Intervention Name(s)
    Melatonin 10 MG Oral Tablet
    Intervention Description
    Group B will receive the pharmacology treatment with 10 mg Melatonin. One capsule orally at night for 60 days.
    Intervention Type
    Drug
    Intervention Name(s)
    Hydroxycobalamin
    Intervention Description
    Group C will receive the pharmacology treatment with 1 mg hydroxycobalamin (vitamin B12). One capsule daily for 60 days.
    Intervention Type
    Drug
    Intervention Name(s)
    Centrum
    Other Intervention Name(s)
    Citoneurone [Cytidine + Hydroxocobalamin, + Uridine]
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Neurosensory Activity
    Description
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Time Frame
    pre-operative
    Title
    Neurosensory Activity
    Description
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Time Frame
    1 day postoperative
    Title
    Neurosensory Activity
    Description
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Time Frame
    3 day postoperative
    Title
    Neurosensory Activity
    Description
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Time Frame
    2 weeks postoperative.
    Title
    Neurosensory Activity
    Description
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Time Frame
    1 month postoperative
    Title
    Neurosensory Activity
    Description
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Time Frame
    2 month postoperative
    Title
    Neurosensory Activity
    Description
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Time Frame
    6 month postoperative
    Title
    Neurosensory Activity
    Description
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Time Frame
    12 month postoperative
    Title
    Neurosensory Activity
    Description
    Presence or absense of symptoms and signs such as hypoesthesia, pain, anesthesia, numbness, among others
    Time Frame
    18 month postoperative
    Secondary Outcome Measure Information:
    Title
    Subjective Test
    Description
    Subjective testing using a questionnaire and visual analogue scale. 0 = normal sensation, 10= more severe sensory deficit.
    Time Frame
    pre-operative, at day 1 and 3, at week 2, and at month 1, 2, 6, 12 and 18 after surgery.
    Title
    Objetive Test
    Description
    The Semmes-Weinstein (SW) test of sensitivity to touch/pressure will be used.
    Time Frame
    pre-operative, at day 1 and 3, at week 2, and at month 1, 2, 6, 12 and 18 after surgery.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    13 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Pedro Sole, DMD, OMFS
    Phone
    +56 9 9235 2728
    Email
    psole@uic.es
    First Name & Middle Initial & Last Name or Official Title & Degree
    Maximiliano Bravo, DMD
    Phone
    +56 9 7690 0878
    Email
    mabravo9@uc.cl
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Pedro Sole, DMD, OMFS
    Organizational Affiliation
    Universidad de Los Andes
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    Individual participant data will not be available due to anonymity and ethical considerations.
    Citations:
    PubMed Identifier
    28318920
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    11936397
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    32631751
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    20784403
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    35606209
    Citation
    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.
    Results Reference
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    PubMed Identifier
    11078134
    Citation
    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.
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    PubMed Identifier
    21071118
    Citation
    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.
    Results Reference
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    PubMed Identifier
    17681774
    Citation
    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.
    Results Reference
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    PubMed Identifier
    17719387
    Citation
    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.
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    Pharmacological Treatment on the Recovery of Neurosensory Disturbance After Bilateral Sagittal Split Osteotomy

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