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Genetic Polymorphisms and Their Association With Temporomandibular Disorders (GenPolTMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04694274
Recruitment Status : Recruiting
First Posted : January 5, 2021
Last Update Posted : January 6, 2021
Information provided by (Responsible Party):
Iva Alajbeg, University of Zagreb

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.

Condition or disease Intervention/treatment
Temporomandibular Disorders Orofacial Pain Device: stabilization splint Procedure: physical therapy Device: placebo splint

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Study Type : Observational
Estimated Enrollment : 60 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Genetic Polymorphisms and Their Association With Temporomandibular Disorders
Actual Study Start Date : May 1, 2017
Estimated Primary Completion Date : January 30, 2024
Estimated Study Completion Date : January 30, 2025

Resource links provided by the National Library of Medicine

Group/Cohort Intervention/treatment
group 1
patients with temporomandibular disorders
Device: stabilization splint
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.

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

Device: placebo splint
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 2
healthy control

Primary Outcome Measures :
  1. change from baseline characteristic pain intensity at 6 months [ Time Frame: baseline, 6th month ]

    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.

  2. change from baseline spontaneous pain at 6 months [ Time Frame: baseline, 6th month ]
    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.

Secondary Outcome Measures :
  1. change from baseline range of mouth opening at 6 months [ Time Frame: baseline, 6th month ]
    1. The pain-free opening is defined as the maximum amount that a patient achieves by opening the mouth without feeling pain and is measured as the distance between the incisal edges of the upper and lower central incisors.
    2. Maximum unassisted mouth opening is measured as the distance between the maxillary and mandibular central incisors and defined as the largest amount of opening that a patient can achieve regardless of pain and discomfort.

  2. change from baseline anxiety at 6 months [ Time Frame: baseline, 6th month ]
    the General anxiety disorder questionnaire (GAD-7) (a 7-question questionnaire that assesses the severity of respondents' anxiety symptoms) is used for assessing the severity of anxiety symptoms of the participants. Scale ranges fro 0 to 21, with higher scores mean a worse outcome. Scores of 5, 10, and 15 represent cut-points for mild, moderate, and severe anxiety, respectively.

  3. change from baseline depression at 6 months [ Time Frame: baseline, 6th month ]
    The Patient Health Questionnaire-9 (PHQ-9) is used for measuring the severity of depressive symptoms. Scores range from 0 to 27, with cut-points 5, 10, 15, and 20 represent mild, moderate, moderately severe and severe depression, respectively.

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 59 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04694274

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Contact: Iva Z Alajbeg, PhD 0038514802125
Contact: Ivan Alajbeg, PhD 0038514802124

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School of Dental Medicine, University of Zagreb Recruiting
Zagreb, N/A = Not Applicable, Croatia, 10000
Contact: Iva Z Alajbeg, PhD    00385917930164   
Sponsors and Collaborators
Croatian Science Foundation
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Principal Investigator: Iva Z Alajbeg School of Dental Medicine, University of Zagreb
Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Iva Alajbeg, Prof, University of Zagreb Identifier: NCT04694274    
Other Study ID Numbers: IP-2019-04-6211
First Posted: January 5, 2021    Key Record Dates
Last Update Posted: January 6, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Temporomandibular Joint Disorders
Temporomandibular Joint Dysfunction Syndrome
Facial Pain
Craniomandibular Disorders
Mandibular Diseases
Jaw Diseases
Musculoskeletal Diseases
Joint Diseases
Muscular Diseases
Stomatognathic Diseases
Myofascial Pain Syndromes
Neurologic Manifestations