Marine Lipids Ease Painful TMD (ADAPT)

Safety And Analgesic Efficacy of Marine Lipid Precursors of Specialized Pro-Resolving Mediators in Adults With Chronic Temporomandibular Pain

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 electronic 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Temporomandibular Disorder (TMD)
• Intervention / Treatment: Dietary supplement: SPM Precursor-Enriched Marine Lipid Supplement; Dietary supplement: Medium-Chain Triglyceride Supplement

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne E Sanders, PhD; Phone Number: 919-537-3275; Email: anne_sanders@unc.edu

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SPM precursor marine lipid dietary supplement; Experimental Arm - SPM Precursor Marine Lipid Supplement: Participants receive 2 g/day (1 g twice daily) of SPM Active® softgels containing 18-HEPE, 17-HDHA, and 14-HDHA. Softgels are identical in appearance to placebo. Duration: 8 weeks. Placebo Arm - Medium-Chain Triglyceride (MCT) Supplement: Participants receive 2 g/day (1 g twice daily) of MCT oil softgels, identical in appearance to active supplement. Duration: 8 weeks.	Dietary supplement: SPM 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.
Placebo Comparator: Medium-chain triglyceride dietary supplement; Participants receive 2 grams per day of a placebo supplement, administered as medium-chain triglyceride (MCT) oil softgels. Participants take 1 gram orally twice daily for 8 weeks. The placebo softgels are identical in appearance and packaging to the active supplement. Participants remain in this arm for the full duration of the study.	Dietary supplement: Medium-Chain Triglyceride Supplement; Participants receive matched placebo softgels daily for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in average weekly facial pain intensity	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.	Baseline (week prior to randomization) through Week 8 (final visit, Day 56 ±7)
Rate of treatment-emergent adverse events	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.	From first dose (Visit 1/Randomization, Day 0) through 7 days after the final dose (Visit 3, Day 56 ±7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in TMD pain duration	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).	From Visit 1 (Randomization, Day 0) through 7 days after the final dose (Visit 3, Day 56 ±7)
Change in TMD pain intensity and pain interference	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.	Visit 1 (Randomization, Day 0) to Visit 3 (Final visit, Day 56 ±7)
Change in headache impact	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.	Visit 1 (Randomization, Day 0); Visit 2 (Mid-study visit, Day 28 ±7); Visit 3 (Final visit, Day 56 ±7)
Change in number of painful body sites	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.	Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7)
Change in pressure pain thresholds	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.	Visit 0 (Screening/Baseline, 7-21 days before Visit 1), Visit 3 (Final visit, Day 56 ±7)
Change in state anxiety	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.	Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7)
Change in depression	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.	Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7)
Change in TMD-related quality of life	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.	Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7)
Change in overall status	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.	Visit 2 (Mid-study, Day 28 ±7); Visit 3 (Final visit, Day 56 ±7)

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute of Dental and Craniofacial Research (NIDCR); Metagenics, Inc.
• Investigators: Principal Investigator: Anne E Sanders, PhD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: February 20, 2026
• First Submitted That Met QC Criteria: February 20, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Quality of life; Randomized controlled trial; Migraine; Omega-3 fatty acids; Central sensitization; Orofacial pain; Temporomandibular joint pain; Pain interference; Chronic pain mechanisms; Pressure pain sensitivity; Chronic facial pain; TMD myalgia; TMD arthralgia; Specialized pro-resolving mediators (SPMs); Marine lipid supplement; Dietary supplement intervention; Experimental pain testing; Headache impact; Anxiety and depression in chronic pain; Body pain distribution
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Stomatognathic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Muscular Diseases; Mental Disorders; Joint Diseases; Jaw Diseases; Headache Disorders, Primary; Headache Disorders; Mandibular Diseases; Craniomandibular Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Anxiety Disorders; Migraine Disorders; Temporomandibular Joint Disorders; Facial Pain
• Other Study ID Numbers: 25-0878

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: beginning 9 and continuing for 36 months following publication
• IPD Sharing Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No