Effect of COMT (Catecholamine-O-methyltransferase) Genetic Polymorphisms on Response to Propranolol Therapy in Temporomandibular Disorder

Detailed Summary

Purpose: Primary: To evaluate the efficacy of extended-release (ER) propranolol compared to placebo in the reduction of a pain index in patients with temporomandibular disorder (TMD). Secondary: To determine if extended-release propranolol efficacy varies according to participants' catechol-O-methyltransferase (COMT) genetic polymorphisms and to investigate the efficacy of extended-release propranolol compared with placebo using secondary endpoints. Exploratory: To investigate whether the efficacy of extended-release propranolol in the reduction of the pain index varies according to participants' polymorphisms in 3 other genetic regions and according to various phenotypic characteristics. Participants: 200 patients with chronic TMD will be randomly assigned, in a 1:1 parallel, double-blind fashion, to receive either extended-release propranolol or placebo at one of three study sites: University of North Carolina-Chapel Hill School of Dentistry; University of Florida-Gainesville College of Dentistry; and the State University of New York at Buffalo School of Dental Medicine. Procedures (methods): Randomization will be to either propranolol or placebo. The 10-week study treatment period is divided into: 1 week of drug titration, 8 weeks of drug maintenance, and 1 week of drug tapering. The titration and tapering doses are 60 mg (capsules) once per day orally; the maintenance dose is 60 mg twice per day orally. Participants will attend 6 clinic visits over 12-15 weeks as follows: screening and baseline visit (Visit \[V\] 0, 7-21 days prior to V1); randomization and start of treatment (titration) (V1, study day 0); maintenance visit 2 (V2, 1 week post-randomization, study day 7+3); maintenance visit 3 (V3, 5 weeks post-randomization, study day 35 +/- 7); tapering visit (V4, 9 weeks post-randomization, study day 63 +/- 7); and tapering visit 5 (V5, 11 weeks post-randomization and 1 week after drug tapering ends, study day 77 +/- 7). Depending on the visit, procedures will include: reviews of medical history, weekly alcohol consumption, concomitant therapies and medications, adverse events, compliance, and eligibility; administration/review of questionnaires; blood draw; pregnancy test in women of childbearing potential; and dispensing of study drug.

Study Details

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Interventions