Temporomandibular DisordersGenPolTMDNCT04694274
Genetic Polymorphisms and Their Association With Temporomandibular Disorders
An observational study of Temporomandibular Disorders and Orofacial Pain, run by Croatian Science Foundation at 1 site in Croatia.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 to 59 yearsHealthy volunteers can take part
- Conditions the study is for
- Temporomandibular Disorders, Orofacial Pain
- What is being tested?
- stabilization splint and physical therapy
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteCroatia
- Study dates
- 1 May 2017to 30 Jan 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 59 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
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
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Croatia1 site, 1 recruiting
- Recruiting
School of Dental Medicine, University of Zagreb
Zagreb, N/A = Not Applicable, 10000
Iva Z Alajbeg, PhD, 00385917930164, ialajbeg@sfzg.hr
About this study
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
- Being tested
- stabilization splint, physical therapy, placebo splint
- Medical subject headings
- Temporomandibular Joint Disorders, Facial Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
stabilization splintDevice
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.
physical therapyProcedure or surgery
Home-exercise program included exercises for passive and active stretching, joint mobilization, passive extension, and translational movements to the right, left, and forward.
placebo splintDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| group 1 | patients with temporomandibular disorders Receives: Device: stabilization splint; Procedure: physical therapy; Device: placebo splint | |
| group 2 | healthy control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: baseline, 6th month
Secondary outcomes (3)
change from baseline range of mouth opening at 6 months
- 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.
- 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.
Measured: baseline, 6th month
change from baseline anxiety at 6 months
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.
Measured: baseline, 6th month
change from baseline depression at 6 months
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.
Measured: baseline, 6th month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2021
- Study start1 May 2017
- Primary completion30 Jan 2024 (estimated)
- Study completion30 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Temporomandibular DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Croatian Science Foundation
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Iva Alajbeg, University of Zagreb
- Investigators
- Iva Z Alajbeg, Principal investigator, School of Dental Medicine, University of Zagreb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04694274
- Sponsor's protocol ID
- IP-2019-04-6211
- Acronym
- GenPolTMD
- Status last verified
- Jan 2021
- First submitted
- 31 Dec 2020
- Last updated
- 6 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 29269980Vrbanovic 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.
PubMed 31749451Vrbanovic 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.
PubMed 31170954Vrbanovic 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.
PubMed 30386251Alajbeg 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.
PubMed 27688394Alajbeg 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.
PubMed 32620810Vrbanovic 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.
PubMed 32533874Alajbeg 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.
PubMed 38589630Vrbanovic 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.
PubMed 35254961Gikic 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.
PubMed 33797785
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Polymorphisms and Their Association With Temporomandibular Disorders
- ClinicalTrials.gov ID
- NCT04694274
- Acronym / sponsor ID
- GenPolTMD / IP-2019-04-6211
- Conditions
- Temporomandibular Disorders, Orofacial Pain
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Croatian Science FoundationOther government
- Study start
- 1 May 2017 (actual)
- Primary completion
- 30 Jan 2024 (estimated)
- Study completion
- 30 Jan 2025 (estimated)
- First posted
- 5 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| group 1 | – | Device: stabilization splint, Procedure: physical therapy, Device: placebo splintpatients with temporomandibular disorders |
| group 2 | – | –healthy control |
Who may qualify
- Ages
- 15 to 59 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- 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
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| stabilization splintThe 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. | Device | group 1 |
| physical therapyHome-exercise program included exercises for passive and active stretching, joint mobilization, passive extension, and translational movements to the right, left, and forward. | Procedure or surgery | group 1 |
| placebo splintThe 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. | Device | group 1 |
Primary outcome
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.
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.
3 secondary outcomes
change from baseline range of mouth opening at 6 months
Time frame: baseline, 6th month
change from baseline anxiety at 6 months
Time frame: baseline, 6th month
change from baseline depression at 6 months
Time frame: baseline, 6th month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2021.
- Background: PubMed 29269980Alajbeg 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.
- Background: PubMed 31749451Vrbanovic 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.
- Background: PubMed 31170954Vrbanovic 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.
- Background: PubMed 30386251Vrbanovic 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.
- Background: PubMed 27688394Alajbeg 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.
- Results publication: PubMed 32620810Alajbeg 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.
- Results publication: PubMed 32533874Vrbanovic 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.
- Derived from this study: PubMed 38589630Alajbeg 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.
- Derived from this study: PubMed 35254961Vrbanovic 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.
- Derived from this study: PubMed 33797785Gikic 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Iva Z Alajbeg principal investigator
School of Dental Medicine, University of Zagreb
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Temporomandibular Disorders and Orofacial Pain, run by Croatian Science Foundation at 1 site in Croatia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Iva Z Alajbeg, PhD (0038514802125, ialajbeg@sfzg.hr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change from baseline characteristic pain intensity at 6 months (time frame: baseline, 6th month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04694274, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2021.