Study of Orofacial Pain and PropRANOlol
Condition: Temporomandibular Disorders
MeSH terms: Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome
Intervention: Propranolol ER; Placebo
Intervention description: Capsules given orally according to schedule at Visit 1, Visit 2, Visit 3, and Visit 4.; Gelatin capsules with a microcrystalline cellulose filler manufactured to mimic propranolol ER 60 mg capsules
Intervention MeSH terms: Propranolol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 200.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion:

          -  Diagnostic criteria for TMD: Group II, Masticatory Muscle Disorders, Myalgia

          -  Facial pain for at least 3 months (and at least 10 of the last 30 days at Visit 0)

          -  Average pain intensity rating ≥30 (0-100 numeric rating scale) over the past week or
             average daily pain intensity rating ≥30 on the same scale on at least 3 days over the
             past week

          -  Agrees to terms for continuing/discontinuing certain prescription/over-the-counter
             pain medications throughout participation

          -  Agrees to not commence new prescription medication, injection therapy, occlusal splint
             therapy or certain other pain management techniques throughout participation

          -  Agrees to limit consumption of alcohol to no more than 7 drinks/week (females) and no
             more than 14 drinks/week (males) throughout participation

          -  If a female of childbearing potential, agrees to use of contraception (licensed
             hormonal method, intrauterine device, condoms with contraceptive foam, abstinence, or
             partner vasectomy) throughout participation

          -  Able to understand and comply with study procedures and provide written informed
             consent

        Exclusion:

          -  History of congestive heart failure or certain cardiac conditions including coronary
             artery disease, uncontrolled hypertension, or hypotension

          -  Bronchial asthma, nonallergic bronchospasm, renal failure or dialysis, diabetes
             mellitus, hyperthyroidism, fibromyalgia, or uncontrolled seizures

          -  Currently taking a β-blocker or certain other medications including haloperidol,
             intravenous verapamil, or reserpine

          -  Currently taking an opioid medication

          -  Daily prescription medication, occlusal splint therapy, or an investigational drug or
             treatment for pain management within past 30 days

          -  Injection therapy or certain other pain management techniques within last 2 weeks

          -  Facial trauma or orofacial surgery within past 6 weeks

          -  Active orthodontic treatment

          -  History of major depression or other psychiatric disorder requiring hospitalization
             within past 6 months

          -  Treatment for drug or alcohol abuse within the last year

          -  Smokes 25 or more cigarettes/day

          -  Currently receiving chemotherapy or radiation therapy

          -  Pregnant or breastfeeding