Genetic Polymorphisms and Their Association With Temporomandibular Disorders

NCT04694274 | Unknown DMC

• 1 other identifier: IP-2019-04-6211
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Temporomandibular disorders (TMD) are the most common orofacial pain disorders of non-dental origin with the prevalence of 6.1-10.2%, and incidence of 3.9%. Observable pathology is mostly absent, and the etiology often remains unknown. Since some other painful conditions of unknown origin (eg. fibromyalgia), also imply genetic factors, the aim of the study is to investigate genetic predisposition in relation to the risk for TMD onset. This will be achieved through analysis of polymorphisms in the selected genes in TMD patients (DC/TMD) and matched control subjects. The possibility of involvement of specific polymorphisms in modulation of therapy response will also be investigated. The hypotheses: (I) the Single Nucleotide Polymorphism (SNPs) clustering will be dependent on presence or absence of TMD (comparison of patients with control subjects), and will possibly depend on source of pain, pain intensity, presence of bone changes, psychological features and previous orthodontic therapy, and (II) SNPs will influence the treatment response. Along with anamnestic and clinical examination and occlusal splint therapy, genomic DNA will be analyzed from the buccal swabs. Isolated DNA will be used for the determination of 19 polymorphisms of selected genes using Real-Time PCR method. The analysis of salivary oxidative stress markers and opiorphin will be also performed, as their relationship with TMD has been shown previously. This time, their concentration will be associated with polymorphisms in the promoters of genes responsible for their synthesis. The investigators expect to show that particular gene profile or group of SNPs represent a risk factor for TMD development. Innovative approach of the concept of determining the genetic predisposition for TMD has the potential for development of commercial genetic test with potential for risk estimation in relation to TMD onset. This could enable early interventions and active avoidance of environmental risk factors.

Conditions

Temporomandibular Disorders; Orofacial Pain

Outcome Measures

Primary Outcomes (2)

• change from baseline characteristic pain intensity at 6 months

  The characteristic pain intensity (part of Graded Chronic Pain Scale, GCPS) compute mean of items (pain right now, worst pain, average pain), and multiply by 10. Each item ranges from 0 to 10, with higher scores mean a worse outcome.

  baseline, 6th month

• change from baseline spontaneous pain at 6 months

  For evaluation of spontaneous pain from the temporomandibular joint and the masticatory muscles a 100 mm horizontal Visual analogue scale (VAS) is used. Visual analogue scale ranges from 0 to 100, with higher scores mean a worse outcome.

  baseline, 6th month

Secondary Outcomes (3)

• change from baseline range of mouth opening at 6 months

  baseline, 6th month

• change from baseline anxiety at 6 months

  baseline, 6th month

• change from baseline depression at 6 months

  baseline, 6th month

Study Arms (2)

group 1

patients with temporomandibular disorders

Device: stabilization splint; Procedure: physical therapy; Device: placebo splint

group 2

healthy control

Interventions

stabilization splint DEVICE

The device made of a hard acrylic on stone cast of the upper jaw in the centric relation position. It has a thickness of 1.5 mm at the level of the first molar.

group 1

physical therapy PROCEDURE

Home-exercise program included exercises for passive and active stretching, joint mobilization, passive extension, and translational movements to the right, left, and forward.

group 1

placebo splint DEVICE

The placebo splint was made of thin heat-treatable foil (0.5 mm). The foil was heated and printed over a plaster model of the upper jaw resulting in a very thin film over the occlusal surfaces of all teeth.

group 1

Eligibility Criteria

• Age: 15 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study will include subjects, 15 years and older, with a report of ongoing for a duration of \>3 months and diagnosis of TMD according DC/TMD and age matched control subjects

You may qualify if:

• diagnosis of myofascial pain / arthralgia / painful disc displacement according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD)
• average pain in the last 10 days \>30 mm on a Visual Analogue Scale
• pain duration of at least 3 months
• good oral hygiene
• presence of own natural teeth
• absence of any form of chronic pain in the orofacial region or in other regions of the body

You may not qualify if:

• other orofacial pain conditions including dental pain
• poor oral hygiene, gingivitis or periodontitis
• chronic medical conditions (diabetes, cardiovascular diseases, cancer, and autoimmune diseases) - - -
• neurological and psychiatric disorders
• pregnancy
• causes of headache, unrelated to TMD, listed in the International Classification of Headache Disorders

Sponsors & Collaborators

• Croatian Science Foundation: lead

Study Sites (1)

School of Dental Medicine, University of Zagreb

Zagreb, N/A = Not Applicable, 10000, Croatia

RECRUITING

Related Publications (10)

• Alajbeg IZ, Lapic I, Rogic D, Vuletic L, Andabak Rogulj A, Illes D, Knezovic Zlataric D, Badel T, Vrbanovic E, Alajbeg I. Within-Subject Reliability and between-Subject Variability of Oxidative Stress Markers in Saliva of Healthy Subjects: A Longitudinal Pilot Study. Dis Markers. 2017;2017:2697464. doi: 10.1155/2017/2697464. Epub 2017 Nov 15.

  PMID: 29269980 BACKGROUND

• Vrbanovic E, Alajbeg IZ. Long-term Effectiveness of Occlusal Splint Therapy Compared to Placebo in Patients with Chronic Temporomandibular Disorders. Acta Stomatol Croat. 2019 Sep;53(3):195-206. doi: 10.15644/asc53/3/1.

  PMID: 31749451 BACKGROUND

• Vrbanovic E, Lapic I, Rogic D, Alajbeg IZ. Changes in salivary oxidative status, salivary cortisol, and clinical symptoms in female patients with temporomandibular disorders during occlusal splint therapy: a 3-month follow up. BMC Oral Health. 2019 Jun 6;19(1):100. doi: 10.1186/s12903-019-0791-8.

  PMID: 31170954 BACKGROUND

• Vrbanovic E, Alajbeg IZ, Vuletic L, Lapic I, Rogic D, Andabak Rogulj A, Illes D, Knezovic Zlataric D, Badel T, Alajbeg I. Salivary Oxidant/Antioxidant Status in Chronic Temporomandibular Disorders Is Dependent on Source and Intensity of Pain - A Pilot Study. Front Physiol. 2018 Oct 17;9:1405. doi: 10.3389/fphys.2018.01405. eCollection 2018.

  PMID: 30386251 BACKGROUND

• Alajbeg IZ, Gikic M, Valentic-Peruzovic M. Mandibular Range of Movement and Pain Intensity in Patients with Anterior Disc Displacement without Reduction. Acta Stomatol Croat. 2015 Jun;49(2):119-27. doi: 10.15644/asc49/2/5.

  PMID: 27688394 BACKGROUND

• Alajbeg IZ, Vrbanovic E, Lapic I, Alajbeg I, Vuletic L. Effect of occlusal splint on oxidative stress markers and psychological aspects of chronic temporomandibular pain: a randomized controlled trial. Sci Rep. 2020 Jul 3;10(1):10981. doi: 10.1038/s41598-020-67383-x.

  PMID: 32620810 RESULT

• Vrbanovic E, Alajbeg IZ, Alajbeg I. COVID-19 pandemic and Zagreb earthquakes as stressors in patients with temporomandibular disorders. Oral Dis. 2021 Apr;27 Suppl 3(Suppl 3):688-693. doi: 10.1111/odi.13488. Epub 2020 Jul 13.

  PMID: 32533874 RESULT

• Alajbeg IZ, Vrbanovic E, Alajbeg I, Orabovic I, Naka K, Mrla A, Boucher Y. Time-course of pain and salivary opiorphin release in response to oral capsaicin differ in burning mouth syndrome patients, temporomandibular disorders patients and control subjects. Clin Oral Investig. 2024 Apr 9;28(5):246. doi: 10.1007/s00784-024-05653-y.

  PMID: 38589630 DERIVED

• Vrbanovic E, Zlendic M, Alajbeg IZ. Association of oral behaviours' frequency with psychological profile, somatosensory amplification, presence of pain and self-reported pain intensity. Acta Odontol Scand. 2022 Oct;80(7):522-528. doi: 10.1080/00016357.2022.2042380. Epub 2022 Mar 7.

  PMID: 35254961 DERIVED

• Gikic M, Vrbanovic E, Zlendic M, Alajbeg IZ. Treatment responses in chronic temporomandibular patients depending on the treatment modalities and frequency of parafunctional behaviour. J Oral Rehabil. 2021 Jul;48(7):785-797. doi: 10.1111/joor.13173. Epub 2021 Apr 12.

  PMID: 33797785 DERIVED

MeSH Terms

Conditions

Temporomandibular Joint Disorders; Facial Pain

Interventions

Physical Therapy Modalities

Condition Hierarchy (Ancestors)

Craniomandibular Disorders; Mandibular Diseases; Jaw Diseases; Musculoskeletal Diseases; Joint Diseases; Muscular Diseases; Stomatognathic Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Rehabilitation

Study Officials

• Iva Z Alajbeg

  School of Dental Medicine, University of Zagreb

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Iva Z Alajbeg, PhD

CONTACT

0038514802125; ialajbeg@sfzg.hr

Ivan Alajbeg, PhD

CONTACT

0038514802124; ialajbeg@sfzg.hr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: December 31, 2020
• First Posted: January 5, 2021
• Study Start: May 1, 2017
• Primary Completion: January 30, 2024
• Study Completion: January 30, 2025
• Last Updated: January 6, 2021

Record last verified: 2021-01

Locations

CR (1)