Temporomandibular Disorder (TMD)
Conditions
Keywords
Chronic facial pain, Temporomandibular joint pain, TMD myalgia, TMD arthralgia, Orofacial pain, Specialized pro-resolving mediators (SPMs), Omega-3 fatty acids, Marine lipid supplement, Dietary supplement intervention, Pressure pain sensitivity, Experimental pain testing, Central sensitization, Chronic pain mechanisms, Randomized controlled trial, Pain interference, Headache impact, Anxiety and depression in chronic pain, Quality of life, Migraine, Body pain distribution
Brief summary
The ADAPT study is a single-site, Phase 2b, randomized, quadruple-masked, placebo-controlled trial evaluating an omega-3 dietary supplement enriched with specialized pro-resolving mediator (SPM) precursors in adults with chronic temporomandibular disorder (TMD) pain. The trial will enroll 100 adults aged 18 years or older with examiner-confirmed TMD myalgia or arthralgia will be enrolled at the University of North Carolina at Chapel Hill, Adams School of Dentistry. Participants are randomized 1:1 to receive either the SPM precursor supplement or a matched placebo daily for 8 weeks. Randomization is stratified by sex, and study agents are identical in appearance to maintain masking. The study aims to evaluate whether the SPM precursor supplement: Reduces facial pain intensity compared with placebo. Changes pressure pain sensitivity at the jaw and other standard body sites. Affects other aspects of chronic pain, including duration, interference with daily activities, headache burden, anxiety, depression, jaw-related quality of life, and overall patient-reported change. Participants will record their daily facial pain intensity in paper diaries, complete short questionnaires at baseline, Week 4, and Week 8, and undergo experimental pain testing with a handheld algometer at baseline, Week 4, and Week 8. Safety is monitored through the documentation of all adverse events throughout the study period.
Detailed description
Study Overview Participant Procedures Screening/Baseline (Visit 0-1): DC-TMD examination to confirm eligibility; review of medications and health history; baseline questionnaires; pressure pain threshold testing; body manikin pain mapping. Daily Diaries: Participants record facial pain intensity (0-100 NRS) each day for 8 weeks. Mid-study Assessment (Week 4, Visit 2): Questionnaires for pain, mood, quality of life; pressure pain threshold testing. Final Visit (Week 8, Visit 3): Repeat questionnaires, pressure pain testing, and body manikin assessments; blood collection for polyunsaturated fatty acid (PUFA)/oxylipin analysis. Follow-up Call (1 week post-intervention): Safety check for adverse events. Study Duration Total participation: up to 12 weeks (pre-screening, 8-week intervention, 1-week follow-up). Assessments at baseline, Week 4, Week 8, and follow-up call. Population and Recruitment Adults ≥18 years with examiner-confirmed TMD myalgia or arthralgia. Participants of all races and ethnicities are eligible; anticipated demographics: \ 77% female, 6% Hispanic, 83% White, 8% African American, 9% other. Overall Goal To provide high-quality evidence on the effects of omega-3 SPM precursors on facial pain, pressure pain sensitivity, psychosocial distress, headache burden, jaw-related quality of life.
Interventions
DIETARY_SUPPLEMENTSPM Precursor-Enriched Marine Lipid Supplement
Participants receive omega-3 SPM precursor-enriched marine lipid softgels administered daily for 8 weeks at the dose specified in the protocol.
DIETARY_SUPPLEMENTMedium-Chain Triglyceride Supplement
Participants receive matched placebo softgels daily for 8 weeks.
Sponsors
University of North Carolina, Chapel Hill
National Institute of Dental and Craniofacial Research (NIDCR)
Metagenics LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants, care providers, investigators, and outcomes assessors are unaware of group assignment. Active and placebo softgels are identical in appearance and packaging. Randomization codes are maintained by an independent data manager until study completion.
Intervention model description
This is a single-site, Phase 2b, randomized, quadruple-masked (Participant, Care Provider, Investigator, Outcomes Assessor), placebo-controlled trial with parallel assignment. Participants are randomized 1:1 to receive either an omega-3 SPM precursor-enriched marine lipid dietary supplement or a matched placebo dietary supplement. Randomization is stratified by sex to ensure balance across arms. Study agents are administered daily for 8 weeks. The primary outcome is daily facial pain intensity recorded via symptom diaries; secondary outcomes include self-administered questionnaires and pressure pain thresholds measured using a handheld algometer.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Pre-screening (before Visit 0): * Age ≥18 years. * Pain in jaws, temples, ears, or in front of ears at least 5 days in the past 30 days, occurring monthly over the last 3 months. * Pain not due to toothache or ear infection. * Pain intensity ≥30 on a 0-100 numeric rating scale (NRS) during the week before pre-screening. * Willing to provide written informed consent and follow all study procedures. * Able to be contacted reliably during the study period. Visit 0 - Screening/Baseline: * Meets all pre-screening criteria above. * Examiner-confirmed TMD diagnosis (myalgia or arthralgia) per DC-TMD criteria. * Discontinues omega-3 supplements prior to randomization and agrees not to use them during the study. * Will not initiate new occlusal splint therapy during the study. Participants already using a splint ≥30 days prior may continue. * Maintains stable facial pain management regimen: * No changes to regularly scheduled daily pain medications. * No initiation of new facial pain treatments (pharmacologic, injectable, or non-pharmacologic). * Episodic prescription pain medications discontinued prior to randomization, except NSAIDs, acetaminophen, or low-dose aspirin. Visit 1 - Randomization: * Completes ≥4 of 7 daily symptom diary (DSD) entries before Visit 1. * Average weekly pain ≥30 on 0-100 NRS, or ≥30 on at least 4 days that week. Exclusion (Assessed at pre-screening and/or Visit 0): * Allergy or hypersensitivity to fish or seafood. * Botulinum toxin injections for facial pain within past 3 months. * Facial trauma or orofacial surgery within past 6 weeks. * History of renal failure or dialysis. * History of hyperthyroidism. * Immunocompromised state or autoimmune disorder. * History of seizure disorder or uncontrolled seizures. * Use of opioid medications in the past 30 days. * Pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in average weekly facial pain intensity | Baseline (week prior to randomization) through Week 8 (final visit, Day 56 ±7) | Net change from baseline to Week 8 in average weekly facial pain intensity, calculated as the mean of daily entries recorded in the Daily Symptom Diary (DSD). Higher scores indicate worse pain. |
| Rate of treatment-emergent adverse events | From first dose (Visit 1/Randomization, Day 0) through 7 days after the final dose (Visit 3, Day 56 ±7) | Rate of participants experiencing any adverse event (AE) that first appears or worsens after starting the study intervention and up to 7 days after the last dose. Investigators record onset, duration, severity, and relatedness to the study intervention. This measure evaluates the safety of the SPM precursor marine lipid supplement compared with placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in TMD pain duration | From Visit 1 (Randomization, Day 0) through 7 days after the final dose (Visit 3, Day 56 ±7) | Change from baseline to Week 8 (Visit 3) in the percentage of waking time with facial pain, expressed in percentage points, based on daily diary entries (0-100 scale). |
| Change in TMD pain intensity and pain interference | Visit 1 (Randomization, Day 0) to Visit 3 (Final visit, Day 56 ±7) | Change from baseline to Week 8 (Visit 3) in TMD pain intensity (current, worst, and average) and interference with daily activities. Assessed using the Graded Chronic Pain Scale (0-10 scale), with higher scores indicating worse pain and greater interference. |
| Change in headache impact | Visit 1 (Randomization, Day 0); Visit 2 (Mid-study visit, Day 28 ±7); Visit 3 (Final visit, Day 56 ±7) | Change from baseline to Week 8 (Visit 3) in headache impact measured with the Headache Impact Test-6 (HIT-6). Scores range 36-78, with higher scores indicating greater headache-related impact. |
| Change in number of painful body sites | Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7) | Change from baseline to Week 8 (Visit 3) in the number of anatomical locations marked as painful on anterior and posterior body manikins (range 0-42), with higher scores indicating more widespread pain. |
| Change in pressure pain thresholds | Visit 0 (Screening/Baseline, 7-21 days before Visit 1), Visit 3 (Final visit, Day 56 ±7) | Change from baseline to Week 8 (Visit 3) in pressure pain thresholds (kg) measured bilaterally at five anatomical sites: temporalis, masseter, TM joint, trapezius, and lateral epicondyle. Up to 5 trials per site are performed until two measurements differ by ≤0.2 kg. Higher numbers indicate lower pain sensitivity. |
| Change in state anxiety | Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7) | Change from Day 0 to Week 8 (Visit 3) in state anxiety measured using the State subscale of the State-Trait Anxiety Inventory (range 20-80), with higher scores indicating greater anxiety. |
| Change in depression | Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7) | Change from Day 0 to Week 8 (Visit 3) in depressive symptoms measured using the Symptom Checklist-90 (SCL90) Depression subscale (range 0-48), with higher scores indicating more severe symptoms. |
| Change in TMD-related quality of life | Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7) | Change from Day 0 to Week 8 (Visit 3) in the impact of TMD on daily activities, pain, psychological well-being, and other aspects of quality of life. Measured with a summary score using the Oral Health Impact Profile-TMD (OHIP-TMD, range 0-88), with higher scores indicating greater adverse impact. |
| Change in overall status | Visit 2 (Mid-study, Day 28 ±7); Visit 3 (Final visit, Day 56 ±7) | Change at Weeks 4 (Visit 2) and 8 (Visit 3) in participants' perceived change in activities, symptoms, emotions, and quality of life related to facial pain, assessed using the Patient Global Impression of Change questionnaire (7-point scale), with higher scores reflecting greater improvement. |
Countries
United States
Contacts
CONTACTAnne E Sanders, PhD
CONTACTLorraine M King
PRINCIPAL_INVESTIGATORAnne E Sanders, PhD
University of North Carolina, Chapel Hill
Outcome results
None listed