Study of Orofacial Pain and PropRANOlol

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.

Timeline

Start

2015-08-20

Primary completion

2018-04-04

Completion

2018-04-25

Publications

• Background Tchivileva IE, Lim PF, Smith SB, Slade GD, Diatchenko L, McLean SA, Maixner W. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. Pharmacogenet Genomics. 2010 Apr;20(4):239-48. doi: 10.1097/FPC.0b013e328337f9ab.
• Background Gursoy S, Erdal E, Herken H, Madenci E, Alasehirli B, Erdal N. Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome. Rheumatol Int. 2003 May;23(3):104-7. doi: 10.1007/s00296-002-0260-5. Epub 2002 Oct 22.
• Background Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, Max MB, Makarov SS, Maixner W. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005 Jan 1;14(1):135-43. doi: 10.1093/hmg/ddi013. Epub 2004 Nov 10.
• Tchivileva IE, Ohrbach R, Fillingim RB, Lin FC, Lim PF, Arbes SJ Jr, Slade GD. Clinical, psychological, and sensory characteristics associated with headache attributed to temporomandibular disorder in people with chronic myogenous temporomandibular disorder and primary headaches. J Headache Pain. 2021 May 22;22(1):42. doi: 10.1186/s10194-021-01255-1.
• Tchivileva IE, Ohrbach R, Fillingim RB, Lim PF, Giosia MD, Ribeiro-Dasilva M, Campbell JH, Hadgraft H, Willis J, Arbes SJ Jr, Slade GD. Effect of comorbid migraine on propranolol efficacy for painful TMD in a randomized controlled trial. Cephalalgia. 2021 Jun;41(7):839-850. doi: 10.1177/0333102421989268. Epub 2021 Feb 9.
• Slade GD, Fillingim RB, Ohrbach R, Hadgraft H, Willis J, Arbes SJ Jr, Tchivileva IE. COMT Genotype and Efficacy of Propranolol for TMD Pain: A Randomized Trial. J Dent Res. 2021 Feb;100(2):163-170. doi: 10.1177/0022034520962733. Epub 2020 Oct 8.
• Tchivileva IE, Hadgraft H, Lim PF, Di Giosia M, Ribeiro-Dasilva M, Campbell JH, Willis J, James R, Herman-Giddens M, Fillingim RB, Ohrbach R, Arbes SJ Jr, Slade GD. Efficacy and safety of propranolol for treatment of temporomandibular disorder pain: a randomized, placebo-controlled clinical trial. Pain. 2020 Aug;161(8):1755-1767. doi: 10.1097/j.pain.0000000000001882.
• Sanders AE, Slade GD, Fillingim RB, Ohrbach R, Arbes SJ Jr, Tchivileva IE. Effect of Treatment Expectation on Placebo Response and Analgesic Efficacy: A Secondary Aim in a Randomized Clinical Trial. JAMA Netw Open. 2020 Apr 1;3(4):e202907. doi: 10.1001/jamanetworkopen.2020.2907.

Drugs

Indications