Managing chronic Myalgia Temporomandibular Disorder (M-TMD): a pragmatic randomised controlled trial of Botulinum toxin type A, Lidocaine, and Amitriptyline/Gabapentin, with internal pilot and cost-effectiveness analysis (MiTiGate trial)

BACKGROUND: Temporomandibular disorders (TMD) affect 1 in 15 people. Myalgia TMD (M-TMD) is most common and causes facial pain, greatly affecting patients' quality of life. Self-management is the initial, non-specialist treatment for acute M-TMD. Despite this, 49% of cases develop chronic M-TMD (=3 months' duration) requiring specialist care. For chronic M-TMD, specialists provide NICE's standard of care (amitriptyline/gabapentin). Injectable treatments for the painful muscles are also available. There is, however, no high-quality evidence identifying the most effective and cost-effective first-line specialist treatment: botulinum toxin type A, lidocaine, or amitriptyline/gabapentin. RESEARCH QUESTION: Are three cycles of botulinum toxin type A (Botox, AbbVie [BTX]) or lidocaine injections superior to treatment as usual (TAU: amitriptyline and/or gabapentin) in improving quality of life and reducing pain intensity in chronic M-TMD at 36 weeks (wks) of treatment and which is cost-effective? DESIGN: A pragmatic, phase III definitive, three-arm parallel-group, individually randomised, open-label, controlled superiority trial with an internal pilot comparing the clinical- and cost-effectiveness and safety of BTX injections, lidocaine 2% injections, TAU (amitriptyline and/or gabapentin). SETTING: 12 UK hospital sites providing recruitment and intervention. Adjunctive recruitment: self- and primary care referral. POPULATION: Adults with chronic M-TMD. INCLUSION: Age =18; M-TMD diagnosed by the Diagnostic Criteria for TMD; Characteristic Pain Intensity=40 for =3 months and failed self-management. EXCLUSION: Contraindication to, or currently using trial intervention; other TMD sub-type; neuropathic pain; fibromyalgia; pregnancy or lactation; substance use disorder. CO-PRIMARY OUTCOMES: Disorder-specific quality of life measured by Oral Health Impact Profile-TMD (OHIP-TMD, 0-88 score) and Characteristic Pain Intensity (CPI, 0-100 score) at 36wks. Primary economic outcome: incremental cost per quality-adjusted life year gained of the most effective treatment compared to other treatments at 36wks. SECONDARY OUTCOMES: Jaw function limitation scale; EQ-5D-5L; PHQ-4, psychosocial distress; global impression of change; adverse effects profile and serial photos; analgesia use; sleep quality. Qualitative process evaluation during internal pilot, followed by longitudinal interviews to explore treatment experiences. INTERVENTIONS: Participants will be randomised 1:1:1 to: 1) BTX injections 2) Lidocaine 2% injections 3) TAU: amitriptyline and/or gabapentin Interventions provided over 36wks: 3 cycles of injections or medication consults at 0,12, & 24wks. SAMPLE SIZE: To conclude that BTX or Lidocaine is superior to TAU, statistically significant differences in both co-primary outcomes are needed at 36wks; therefore, adjustments for multiple testing are not required. Overall, 663 patients will provide an overall power of 90% for testing BTX vs TAU and Lidocaine vs TAU allowing for 27% attrition to detect a 6-unit change in OHIP-TMD and 10-units on CPI (minimally important clinical changes). TIMELINES: Internal pilot with stop/go criteria ends at 12 months. The study runs for 48 months (23 months recruitment). IMPACT & DISSEMINATION: The team has expertise in innovative dissemination and shaping national/international policy. Our expertise/plans mean the study is well-positioned to influence guidance and clinical practice.