This 2-part study will evaluate the effectiveness and side effects of two anti-inflammatory
drugs for relieving pain and improving jaw function in patients with temporomandibular
disorder (TMD). Part 1 will evaluate celecoxib (Celebrex); Part 2 will evaluate etanercept
(Enbrel). The Food and Drug Administration has approved both of these drugs for treating
certain forms of arthritis.
Patients between the ages of 18 and 65 years with painful jaw joint conditions may be
eligible for this study. Candidates will complete several written questionnaires about
their jaw condition and will undergo a medical history, complete TMD evaluation, blood and
urine tests, and imaging studies of the temporomandibular joint, such as X-rays and magnetic
resonance imaging. Patients will rate the quality and intensity of their pain before
beginning treatment. At certain periods during the study, they will also keep a pain diary,
twice a day recording the intensity and magnitude of their pain.
Part 1 - Celecoxib: Patients will be randomly assigned to receive either 1) celecoxib twice
a day by mouth; 2) naproxen (a non-steroidal anti-inflammatory drug) twice a day by mouth;
or 3) a placebo (inactive pill) twice a day by mouth.
Part 2 - Etanercept: Patients will be randomly assigned to receive either 1) etanercept
injected under the skin or 2) saline (an inactive placebo) injected under the skin.
Patients in this group will also undergo two aspirations of fluid from the jaw joint - once
before treatment begins and again 6 weeks later. For this procedure, the joint is numbed
with an anesthetic and then a needle is inserted into the jaw space to withdraw fluid, which
will be analyzed for inflammatory processes in the joint.
All patients will have a final evaluation 6 weeks after beginning treatment, including a TMD
physical examination, laboratory and X-ray tests as required. The pain diary and
questionnaires will be collected at this visit.
The proposed clinical trial will consist of two parallel studies. In the first part of the
study, we will evaluate the analgesia and adverse effects of celecoxib, a COX-2 inhibitor in
comparison to naproxen and placebo of patients with temporomandibular disorders (TMD).
Celecoxib, is in oral anti-inflammatory and analgesic agent that acts by selectively
inhibiting cyclooxygenase 2 (COX-2) and is not expected to cause the typical
gastrointestinal, and platelet-related side effects associated with inhibition of the COX-1
enzyme. Decrease in pain, dysfunction and improvement in quality of life will be assessed
at base line and after 6-week follow-up. Successful demonstration of an enhanced
therapeutic effect or reduced toxicity may provide a basis for clinical use of selective
COX-2 inhibitors in patients with painful TMD.
In a second group of carefully selected patients, we will evaluate the short-term effect
etanercept (Enbrel) in comparison to placebo in patients who had pain and tenderness to
palpation in the temporomandibular joint (TMJ osteoarthritis) of at least three month
duration and who had not responded to conservative treatment. Etanercept is a biologic
modifier that binds specifically to tumor necrosis factor alpha (TNF alpha). The mechanism
of action of etanercept is competitive inhibition of TNF binding to cell-surface TNF
receptors (TNFR), preventing TNF-mediated cellular responses by rendering TNF biologically
inactive. Subjects will be randomly assigned to either etanercept or placebo
administration. At baseline and at 6-week follow up individual outcomes will be assessed
such as pain, mandibular range of motion along with the analysis of the sample synovial
fluid level of TNF alpha. By studying the joint fluid levels of TNF alpha, we will learn
more about the development of the local inflammatory process in the joint, which will help
in predicting the prognosis for patients with these TM joint disorders. Positive findings
will also provide clinical implications of etanercept in patients with painful TMJ
Recruitment will include patients with early onset of temporomandibular disorder, whose
primary diagnosis consists of anterior disc displacements with reduction as defined by the
Research Diagnostic Criteria (RDC).
Subjects are required to have preauricular pain for a minimum of one month, a primary TMD
diagnosis of TMJ disc displacement, and clinical and radiographic evidence of
Subjects who had undergone any TMJ surgery within the preceding 6 months in any active way
will be excluded as will those who are taking regularly analgesic, anti-inflammatory,
steroids or narcotics medications.
Further exclusion criteria will be patients who have any TMJ growth disturbances.
Patients with red, hot, swollen, tendered TM joints, or those by medical history consist
of infectious arthritis, crystal induced arthropathies, and musculoskeletal disorders will
Patients will be screened for any positive history of liver or kidney dysfunctions.
Patients who have known hypersensitivity to celecoxib, are allergic to sulfonamides, or
have demonstrated allergic-type reactions after taking aspirin or other NSAIDs will be
Subjects that have primary psychiatric disease or score above average or higher in
comparison with normative scores on Symptom Checklist (SCL-90R) will be able to
Subjects with any obvious occlusal disturbances such as cross-bite, open-bite, full
dentures will be disqualified.
Children under the age of 18 will be excluded from the study.
Pregnant women will not be included in the study.
For the etanercept study, we will recruitment patients who are in the later stage of
temporomandibular disorder, who are not responding to standard non-surgical TMD therapy
(i.e., splints, physical therapy, biofeedback, trigger point injections), whose primary
diagnosis consists of TMJ osteoarthritis as defined by the Research Diagnostic Criteria.
Subjects are required to have preauricular pain for a minimum of three months with
clinical and radiographic evidence TMJ arthritis.
Subjects who had undergone TMJ surgery within the preceding 6 months in any active way
will be excluded.
Subjects that are taking regularly steroids or narcotics medications will be excluded.
Further exclusion criteria will be presence of TMJ growth disturbances. Patients with
red, hot, swollen, tendered TM joints, TMJ infections or those with medical history
consist of infectious arthritis, crystal induced arthropathies, and musculoskeletal
disorders will be disqualified.
Patients with sepsis or with known hypersensitivity to etanercept or any of its components
will be excluded from the study.
Any patients with a medical history of diabetes, congestive heart failure, or any chronic
infections will be excluded.
Children under the age of 18 will not be included.
Pregnant women will not be included.