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Not yet recruitingNCT07437313ADAPTUpdated Aug 31, 2026

Marine Lipids Ease Painful TMD

An interventional study of SPM Precursor-Enriched Marine Lipid Supplement and Medium-Chain Triglyceride Supplement in Temporomandibular Disorder (TMD), sponsored by University of North Carolina, Chapel Hill. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-31.

Sponsored by University of North Carolina, Chapel Hill · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
100
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Temporomandibular Disorder (TMD)

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
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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.
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
100 participants (estimated)

Study arms

  • 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

  • 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

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.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline (week prior to randomization) through Week 8 (final visit, Day 56 ±7)

  2. 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.

    Time frame: From first dose (Visit 1/Randomization, Day 0) through 7 days after the final dose (Visit 3, Day 56 ±7)

Secondary outcomes

  1. 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).

    Time frame: From Visit 1 (Randomization, Day 0) through 7 days after the final dose (Visit 3, Day 56 ±7)

  2. 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.

    Time frame: Visit 1 (Randomization, Day 0) to Visit 3 (Final visit, Day 56 ±7)

  3. 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.

    Time frame: Visit 1 (Randomization, Day 0); Visit 2 (Mid-study visit, Day 28 ±7); Visit 3 (Final visit, Day 56 ±7)

  4. 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.

    Time frame: Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7)

  5. 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.

    Time frame: Visit 0 (Screening/Baseline, 7-21 days before Visit 1), Visit 3 (Final visit, Day 56 ±7)

  6. 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.

    Time frame: Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7)

  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.

    Time frame: Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7)

  8. 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.

    Time frame: Visit 1 (Randomization, Day 0); Visit 3 (Final visit, Day 56 ±7)

  9. 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.

    Time frame: Visit 2 (Mid-study, Day 28 ±7); Visit 3 (Final visit, Day 56 ±7)

06

Study locations

1 site
  • University of North Carolina at Chapel Hill
    Chapel Hill, North Carolina 27599, United States
07

References and documents

Individual participant data

Plan to share: Yes — 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.

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07437313
Lead sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute of Dental and Craniofacial Research (NIDCR), Metagenics LLC
Responsible party
Sponsor
First posted
Feb 27, 2026
Start date
Sep 25, 2026 (estimated)
Primary completion
Jan 2030 (estimated)
Completion
Feb 2030 (estimated)
Last update
Aug 31, 2026

Study contacts

Anne E Sanders, PhD
Contact
adaptsms@adapt.study
(919) 246-5833
Lorraine M King
Contact
adaptsms@adapt.study
(919) 246-5833
Anne E Sanders, PhD
principal investigator · University of North Carolina, Chapel Hill

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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