Oxidative Stress and Opiorphin in Temporomandibular Disorders

NCT03029494 | Unknown DMC FDA Device

• 1 other identifier: IP- 2014-09-3070
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to quantify salivary oxidative stress biomarkers in patients with temporomandibular disorders and to quantify recently isolated endogenous peptide opiorphin in saliva of these patients. As chronic exposure to stress may cause hyperalgesia as a result of the stress response in the hypothalamic-pituitary-adrenal axis, aim is to test this as an underlying mechanism by correlating opiorphin and oxidative stress markers to salivary cortisol levels. The aim is to assess the association of oxidative stress salivary biomarkers with muscle and joint pain and to measure opiorphin, a potential biomarker of different pathological states.

Conditions

Temporomandibular Disorders

Keywords

oxidative stress; saliva

Outcome Measures

Primary Outcomes (1)

• Change of salivary oxidative stress markers concentration

  Oxidative stress markers will be measured using spectrophotometric methods. Opiorphin levels will be measured by HPLC-MS/MS method, originally developed and validated by team members (Brkljacic L, Sabalic M, Salaric I, Jeric I, Alajbeg I et al, J Chromatogr B Analyt Technol Biomed Life Sci. 2011). The change of the single marker (opiorphin) concentration between the two time points is a measure of clinical efficacy of applied treatment modality. In control group (healthy patients) measurement of oxidative stress markers and opiorphin will be performed only at first appointment in order to compare them with TMD patients baseline levels.

  baseline, 6th month

Secondary Outcomes (4)

• Change of pain intensity in TMD patients

  baseline, 3rd month, 6th month

• The quality of life change in TMD patients

  baseline, 6th month

• Change in the amount of maximal comfortable mouth opening in TMD patients

  baseline, 6th month

• Change in the perceived stress

  baseline, 6th month

Study Arms (3)

Treatment 1: stabilization splint, placebo oral tablet

EXPERIMENTAL

stabilization splint during night and 1 placebo oral tablet daily, for 6 months

Device: stabilization splint; Drug: Placebo Oral Tablet

Treatment 2: placebo splint, vitamin C

ACTIVE COMPARATOR

placebo splint during night and 1000 mg Vitamin C tablet daily, for 6 months

Device: placebo splint; Dietary Supplement: Vitamin C

Control group

NO INTERVENTION

determination of oxidative stress biomarkers and cortisol in saliva of healthy control subjects

Interventions

stabilization splint DEVICE

Hard acrylic type of splint with full coverage of occlusal surfaces of upper teeth, with a thickness of about 1.5 mm at the level of the first molar.

Also known as: occlusal splint

Treatment 1: stabilization splint, placebo oral tablet

Placebo Oral Tablet DRUG

sugar pill manufactured to mimic 1000 mg Vitamin C

Treatment 1: stabilization splint, placebo oral tablet

placebo splint DEVICE

Ineffectively designed oral appliance: an acrylic palatal plate will be used (without influence on occlusion, TMJ and masticatory muscles).

Treatment 2: placebo splint, vitamin C

Vitamin C DIETARY_SUPPLEMENT

1000 mg

Also known as: ascorbic acid

Treatment 2: placebo splint, vitamin C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• for TMD patients: diagnosis of TMD using Croatian version of research diagnostic criteria for temporomandibular disorders (RDC/TMD)
• for control group: gender- and age-matched healthy volunteers

You may not qualify if:

• for TMD patients: patients younger than 18 years; smoking; other local diseases and/or systemic disorders; the use of anti-inflammatory drugs, analgesics and/or muscle relaxants; individuals who had already been under treatment for TMD
• for control group: younger than 18 years; cardiac/circulatory/metabolic/muscle abnormalities; smoking; the use of medications, supplements or dietary aids that might affect the outcome results

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 (11)

• De Leeuw R, Bertoli E, Schmidt JE, Carlson CR. Prevalence of post-traumatic stress disorder symptoms in orofacial pain patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005 May;99(5):558-68. doi: 10.1016/j.tripleo.2004.05.016.

  PMID: 15829878 RESULT

• De Leeuw R, Bertoli E, Schmidt JE, Carlson CR. Prevalence of traumatic stressors in patients with temporomandibular disorders. J Oral Maxillofac Surg. 2005 Jan;63(1):42-50. doi: 10.1016/j.joms.2004.04.027.

  PMID: 15635556 RESULT

• Kawai Y, Kubota E, Okabe E. Reactive oxygen species participation in experimentally induced arthritis of the temporomandibular joint in rats. J Dent Res. 2000 Jul;79(7):1489-95. doi: 10.1177/00220345000790071001.

  PMID: 11005733 RESULT

• Rodriguez de Sotillo D, Velly AM, Hadley M, Fricton JR. Evidence of oxidative stress in temporomandibular disorders: a pilot study. J Oral Rehabil. 2011 Oct;38(10):722-8. doi: 10.1111/j.1365-2842.2011.02216.x. Epub 2011 Apr 4.

  PMID: 21457291 RESULT

• Salaric I, Sabalic M, Alajbeg I. Opiorphin in burning mouth syndrome patients: a case-control study. Clin Oral Investig. 2017 Sep;21(7):2363-2370. doi: 10.1007/s00784-016-2031-9. Epub 2016 Dec 24.

  PMID: 28013436 RESULT

• Turp JC, Komine F, Hugger A. Efficacy of stabilization splints for the management of patients with masticatory muscle pain: a qualitative systematic review. Clin Oral Investig. 2004 Dec;8(4):179-95. doi: 10.1007/s00784-004-0265-4. Epub 2004 Jun 4.

  PMID: 15179561 RESULT

• Miricescu D, Totan A, Calenic B, Mocanu B, Didilescu A, Mohora M, Spinu T, Greabu M. Salivary biomarkers: relationship between oxidative stress and alveolar bone loss in chronic periodontitis. Acta Odontol Scand. 2014 Jan;72(1):42-7. doi: 10.3109/00016357.2013.795659. Epub 2013 Jul 22.

  PMID: 23869629 RESULT

• Lawaf S, Azizi A, Tabarestani T. Comparison of Serum and Salivary Antioxidants in Patients with Temporomandibular Joint Disorders and Healthy Subjects. J Dent (Tehran). 2015 Apr;12(4):263-70.

  PMID: 26622281 RESULT

• Wang J, Schipper HM, Velly AM, Mohit S, Gornitsky M. Salivary biomarkers of oxidative stress: A critical review. Free Radic Biol Med. 2015 Aug;85:95-104. doi: 10.1016/j.freeradbiomed.2015.04.005. Epub 2015 Apr 16.

  PMID: 25889823 RESULT

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Temporomandibular Joint Disorders

Interventions

Occlusal Splints; Ascorbic Acid

Condition Hierarchy (Ancestors)

Craniomandibular Disorders; Mandibular Diseases; Jaw Diseases; Musculoskeletal Diseases; Joint Diseases; Muscular Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Orthotic Devices; Orthopedic Equipment; Surgical Equipment; Equipment and Supplies; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• Iva Z Alajbeg, PhD

  School of Dental Medicine, University of Zagreb

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Iva Z Alajbeg, PhD

CONTACT

00385917930164; ialajbeg@sfzg.hr

Ivan Z Alajbeg, PhD

CONTACT

00385915051271; alajbeg@sfzg.hr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: It will be a single-blind interventional study (as placebo splint cannot be mistaken for a stabilization splint by a clinician).
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: TMD patients will be randomized into two treatment groups. Each group will have two sets of interventions: one presumably active treatment and other a placebo: Treatment group 1: stabilization splint and placebo tablet daily. Treatment group 2: placebo (ineffectively designed) splint and 1000 mg Vitamin C tablet (an antioxidant agent) daily.

Study Record Dates

• First Submitted: January 19, 2017
• First Posted: January 24, 2017
• Study Start: October 1, 2015
• Primary Completion: September 30, 2018
• Study Completion: September 30, 2019
• Last Updated: January 24, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)