The Course of Temporomandibular Pain in Response to Mandibular Advancement Therapy Among Adults With Temporomandibular Disorder and Obstructive Sleep Apnea
Phase: NA
Conditions: Myalgia, Apnea, Obstructive Sleep
Sponsor: University of North Carolina, Chapel Hill

 
Temporomandibular Disorder (TMD) Pain in Response to Jaw 
Advancement in People with TMD and Obstructive Sleep Apnea 
 
 
 
NCT number NCT02685202 
Document Date 02/04/2016 
Most recent IRB approval Date  
(for this document version) 02/08/2017 
 

SPECIFIC AIMS 
Two chronic health conditions are treated with oral appliances during sleep. One condition is 
temporomandibular disorder (TMD); a musculoskeletal disorder characterized by pain in the 
masseter muscle and temporomandibular joint. TMD pain is treated with a stabilization splint 
which operates by limiting abnormal muscle activity. The other condition is obstructive sleep 
apnea (OSA). Mild to moderate OSA is treated with a mandibular advancement splint (MAS) 
which holds the mandible in a protruded position to increase the pharyngeal airway space and 
reduce upper airway collapsibility. 
The comorbidity of the two conditions is high. Approximately one in four patients with clinically 
diagnosed TMD has polysomnographic-diagnosed OSA.1 This comorbidity poses a problem for 
management because neither appliance is considered effective in treating both conditions. In 
fact, mandible advancement is assumed to worsen TMD pain.2 However this assumption is not 
well supported by scientific evidence, with some studies finding that mandibular advancement 
actually reduces TMD pain,3,4,5, albeit after a transient increase in TMD pain in some patients. 
Furthermore, anecdotal evidence suggests that mandibular advancement reduces TMD pain 
because it first alleviates OSA severity, implying a causal relationship.  
The overall objective of this study is to characterize the temporal nature of TMD pain in adults 
with comorbid TMD/OSA treated with MAS therapy. It is the first study to monitor adherence to 
MAS therapy objectively in this study population, using a microsensor embedded in the MAS.  
Aim 1: To describe the frequency, duration, and severity of TMD pain symptoms during MAS 
therapy in people with comorbid TMD and OSA. Hypothesis 1: TMD pain symptoms increase 
at MAS treatment onset, then resolve quickly with continued therapy, to decline below 
baseline levels. 
Aim 2: To examine temporal aspects of the therapeutic response. Hypothesis 2: A reduction 
in OSA severity—determined by a reduction in the apnea hypopnea index (AHI)—precedes a 
reduction in TMD pain. 
Aim 3: To explore the relationship between TMD pain intensity and adherence to MAS 
therapy. Hypothesis 3: Greater pain intensity at enrollment is associated with worse 
adherence. Hypothesis 4: Change in pain over time is correlated with change in adherence. 
Our collaboration has expertise in dental sleep medicine, epidemiology and biostatistics. The 
short-term goal is to collect preliminary evidence in support of a NIH Planning Grant (R34) 
proposal. The long-term goal is to translate research findings into clinical practice guidelines to 
address an unmet need in chronic TMD/OSA pain management. 
 

SIGNIFICANCE 
The study is significant because findings will provide the first detailed information of the course 
of pain and sleep-disordered breathing in people with comorbid TMD/OSA. People rate the 
severity of TMD pain as 4.3, on average, on a 0–10 numeric rating scale; similar to ratings for 
chest pain and back pain.6  Prevalence of TMD is 12% 7 and the disorder accounts for 17.8 
million lost work days per year for every 100 million U.S. working adults.8  As many as 1 in 4 
people with TMD have comorbid OSA.1 In the U.S. adult population, prevalence of OSA is 
26%,9 and OSA has public health significance as a risk factor for hypertension,10 stroke,11 
cardiovascular disease12 depression13 and all-cause mortality.11,12   Clinical trials comparing 
mandibular advancement to CPAP, conclude that the two therapies have equivalent 
effectiveness to prevent airway obstructions14,15,16,17,18,19, 20 because the better adherence to 
mandibular advancement therapy offsets its lesser efficacy.  
The study is significant for its potential to translate research findings into clinical practice 
guidelines. There is clinical equipoise in the research questions since mandibular advancement 
is typically contraindicated with TMD, yet the degree of jaw movement in mandibular 
advancement is insufficient to exacerbate TMD pain,3 and any initial increase in pain is 
transient, 4 and that mandibular advancement decreases TMD pain over time.5  
INNOVATION 
It is innovative to investigate treatment of comorbid 
TMD/OSA with mandibular advancement. These 
conditions are rarely studied together, despite their 
frequent coexistence and shared risk factors22. It is 
innovative to begin to explore the basis for a possible 
causal relationship between sleep-disordered breathing 
and TMD pain. Thirdly, it is innovative to objectively 
assess adherence to MAS therapy using a micro-
recorder (Figure 1). To our knowledge adherence has 
not previously evaluated objectively in TMD patients 
being treated with a MAS.   
APPROACH 
Design: This is an interventional study of 12 patients 
receiving non-standard of care therapy for comorbid TMD/OSA. There is no comparison group.  
 
Fig 1.  An example of a micro-recorder, aka 
“compliance chip”, sealed into the upper 
right side of a MAS. Image copied from 
Vanderveken et al., 2013). 21 

Setting: Recruitment and MAS therapy will be conducted at Lane and Associates Family 
Dentistry; a group of 27 dental practices located throughout the Triangle and Triad region of 
North Carolina.  Advantages of using Lane & Associates are: large influx of new dental patients 
every month, fast recruitment,  well-established protocols for screening for TMD and OSA and 
for referral of patients to sleep physicians for evaluation and PSG, standardized protocols for 
oral appliance therapy, and a Dental Sleep Medicine director (Dr. Spencer) who is highly 
experienced also in the management of TMD.  The study coordinator, Ms. Kristin Dillow, is a 
dental hygienist in the UNC School of Dentistry Dental Sleep Clinic who works with Dr. Essick in 
delivering oral appliance therapy. She will travel to the Lane & Associates offices to assist in 
clinical and administrative activities and will manage all data collection for the 12 subjects. The 
Dental Sleep Clinic at the UNC School of Dentistry is not considered adequate to serve as the 
study site because it currently operates only one day a week and accepts referrals for only 
patients without TMD pain.  
Inclusion criteria are men or women aged 30–64 years of any race or ethnicity who meet 
research diagnostic criteria for TMD,23 who rate their TMD pain severity as ≥4 on a 0–10 
numeric rating scale and have no history of treatment for OSA. If taking a prescription 
medication (with the exception of prescription formulations of NSAIDs, acetaminophen, and 
aspirin) episodically for the management of pain, the subject must agree to discontinue its use 
prior to or at the baseline visit. If taking a prescription medication daily for the management of 
pain, must agree to continue the daily use of the medication throughout the 16-week 
observation period. If taking an over-the-counter pain medication daily, the subject must agree 
to continue the daily use throughout the study.  Exclusion criteria are <8 retained teeth per arch; 
tooth mobility; unmanaged periodontal disease; skeletal Class III occlusion; central sleep apnea; 
hypoventilation syndromes; congestive heart failure; and chronic obstructive pulmonary disease.   
Pre-enrollment activities: Patients at Lane and Associates Family Dentistry complete a standard 
TMD screening questionnaire. Those screening positive will be clinically examined against 
Research Diagnostic Criteria for TMD to confirm Group II: Masticatory Muscle Disorders, 1A: 
Myalgia.24 They will also be screened for OSA using the validated STOP-BANG questionnaire.25 
Those at high risk will be referred for evaluation by a sleep physician and a diagnostic PSG, as 
is the standard of care at Lane and Associates.  If the PSG reveals mild to moderate OSA 
(apnea-hypopnea index (AHI) ≥5 and <30), the patient is a candidate for oral appliance therapy, 
pending confirmation of the sleep physician, and thus eligible to enroll in the study.  

Enrollment: Subjects will be consented and assessed for demographics, medical history, and 
medication use. Impressions of the upper and lower dental arches will be recorded, poured in 
dental stone and sent to the lab. A George Gauge will record a protrusive bite registration with 
the jaw advanced 60% from the most retruded position. The custom-made MAS will be fitted 
with a micro-recorder (Braebon DentiTrac Monitor) to assess adherence. We define adherence 
as use of the splint 4 hours/night for ≥70% of nights as is standard practice for CPAP 
therapy.    Home sleep test (HST): Subjects will complete a series (from 2 to 5) two-night HSTs 
using the portable AccuSom device by NovaSom, which collects sleep parameters of AHI, 
minimum oxygen saturation, and snoring indices (Figure 2). Novosom arranges shipment of the 
device and offers 24-hour technical support during the sleep test.  Sleep data are uploaded 
wirelessly from the recorder to an online portal for statistical analysis.  Drs. Essick and Sanders 
have experience using this device in dental sleep medicine research. 
 
Figure 2. Following a baseline home sleep test (HST), 12 participants will enter the study wearing a MAS during sleep 
that protrudes the mandible to 60% of its maximal advancement. This approximates the minimum amount of jaw 
advancement that is expected to be efficacious.  A HST will be repeated at the end of Week #4. If that HST shows 
that the MAS is not efficacious (i.e. has not reduced baseline AHI by ≥50% or the AHI is ≥10**), and if TMD pain is 
not worse, the mandible will be advanced to 70% and the participant will repeat the HST at the end of Week #8. Once 
efficacy is achieved, there is no need for further HSTs. If efficacy is not achieved at the end of Week #8 and if TMD 
pain is not worse, the mandible will be advanced to 75% and the participant will repeat the HST at the end of Week 
#12. If efficacy is not yet achieved and if TMD pain is not worse, the mandibular will be further advanced to 80% and 
the participant will undergo a final HST at the end of Week #16. Once a HST indicates that the MAS is efficacious in 
reducing the AHI, the participant will maintain that level of advancement. The minimum number of HSTs for any one 
participant is 2 (baseline and 4-week follow-up) and the maximum number is 5.  
* If TMD pain symptoms have worsened the study dentist will determine whether jaw advancement should be 
decreased, maintained or increased. Subjects who cannot tolerate the minimum 60% jaw advancement after 8 weeks 
of treatment will return to their sleep physician for alternate therapies for OSA. 
TMD symptoms are recorded daily by the subject and monitored weekly by the study coordinator. 
**Criteria established by the American Board of Dental Sleep Medicine for a successful responder to oral appliance 
therapy include both a reduction in the AHI of ≥>50% from baseline and AHI<10. 

The primary outcome is the course of TMD pain over 16 weeks, computed from the weekly 
mean pain index, and representing the arithmetic mean of daily pain index values in the 
preceding 7-day period. The pain index is the product of the pain intensity score multiplied by 
the pain duration score, each as reported in the Daily Symptom Diary kept by the subject. A 
second measure of pain, also recorded daily, is the Graded Chronic Pain Scale. This comprises 
7 items and assesses 2 dimensions of pain: pain intensity and pain-related disability.  
Secondary outcomes are sleep breathing parameters 
evaluated by HSTs (Figure 3). Since MAS is a well-
established therapy for OSA these outcomes are 
confirmatory only. We will also assess subjective 
sleepiness with the Epworth Sleepiness Scale.  
Adverse effects: The most likely adverse effect is short-
term increase in TMD pain in the first two weeks. 
Subjects will record TMD pain intensity on a 0-10 
numeric rating scale in a daily log. Every week the study 
coordinator will contact each subject by phone to monitor the course of TMD pain symptoms. 
Subjects with increased TMD pain will be clinically assessed by the study dentist and, if 
indicated, the jaw will be returned to a neutral position until TMD pain symptoms resolve.   
Data analysis: The overall analytic approach will emphasize to Aim 1 is to produce basic 
descriptive statistics and graphic plots to explore within-subject temporal changes in TMD pain 
over 16 weeks.  For Aim 1, the time course of the primary outcome of TMD pain will be fitted 
with a linear mixed model applied to the sixteen repeated measures on the twelve subjects 
using a Kenward-Roger degrees of freedom correction for the small number of patients. 
Observed and model-predicted TMD pain estimates will be plotted for each patient over time.  
The approach for Aim 2 is to use time-lagged correlation analysis by adding to the model of Aim 
1 a time-varying indicator variable for whether AHI has been reduced > 50% from baseline and 
that AHI < 10; for missing HST’s by design (Figure 3), last observation carried forward will be 
used to impute this variable so that for the sixteen time points AHI reduction will be 
characterized by a sequence of zeros, and then, when and if AHI is reduced, by a sequence of 
ones of the two time series (i.e. OSA severity, pain trajectory,) to test hypothesis 2 that a 
reduction in mean AHI precedes a reduction in mean TMD pain.  Finally, for Aim 3, pain 
intensity at enrollment and change in pain over time will be compared between patients who 
satisfy the definition for adherence versus those who do not. 
 
Fig 3. The AccuSom home sleep test 
provided by NovaSom. 

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