Clinical Trial: Study of Orofacial Pain and PropRANOlol

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief Summary:

Purpose:

Primary: To evaluate the efficacy of extended-release propranolol compared to placebo for reducing pain in patients with temporomandibular disorder (TMD).

Secondary: To determine if extended-release propranolol efficacy varies according to participants' catechol-O-methyltransferase (COMT) genetic diplotype.

Exploratory: To investigate whether the effect of extended-release propranolol on the incidence of adverse effects, use of rescue medication, or pain index varies according to polymorphisms in the noncoding regions of COMT, adrenergic receptor β2 (ADRβ2), or adrenergic receptor β3 (ADRβ3) genes.

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

Detailed Summary:

"Temporomandibular disorder" (TMD) encompasses all musculoskeletal disorders of the masticatory system and includes myalgia, arthralgia, temporomandibular joint (TMJ) disc displacements, and TMJ degenerative joint diseases. The prevalence of TMD ranges from 6% to 12% in the general population, with muscle dysfunction the most prevalent TMD diagnostic group. TMD is associated with substantial disability and suffering and negatively impacts quality of life. Jaw pain is the most common symptom that compels treatment seeking. In addition to facial pain, TMD patients frequently report comorbid pain conditions such as headache, low back pain, and fibromyalgia. New approaches to TMD therapy are urgently needed to improve clinical outcomes and reduce economic impact of this disorder.

There is currently no FDA-approved product labeled specifically to manage/treat TMD; however, classes of drugs are used to relieve TMD-associated pain, such as non-steroidal anti-inflammatory drugs (NSAIDs), anti-inflammatory drugs, corticosteroids, benzodiazepines, sedative hypnotics, muscle relaxants, opioids, antidepressants, and anticonvulsants - although evidence to establish their efficacy and safety in this population is scarce. Practitioners' justification for their use may be based on poorly controlled clinical trials or clinical trials in other pain disorders such as acute postsurgical dental pain, arthritic pain, chronic lower back pain, and neuropathic pain. Thus, there is a need for controlled clinical trials to better understand the physiological mechanisms responsible for TMD symptoms.

Evidence suggests that enhanced β-adrenergic drive contributes to the pathogenesis of TMD and other complex persistent pain conditions. For example, individuals with myofascial pain conditions have elevated catecholamine levels and augmente
Sponsor: University of North Carolina, Chapel Hill

Current Primary Outcome:

  • Change in the weekly mean pain index after 5 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 3 (study day 35 +/-7) ]
    Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary.
  • Change in the weekly mean pain index after 9 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) ]
    Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary.


Original Primary Outcome:

  • Change in the weekly mean pain index at 5 weeks [ Time Frame: Visit 1 and Visit 3 after 5 weeks of treatment ]
    Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary.
  • Change in the weekly mean pain index at 9 weeks [ Time Frame: Visit 1 and Visit 4 after 9 weeks of treatment ]
    Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary.


Current Secondary Outcome:

  • Change in the weekly mean pain intensity after 5 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 3 (study day 35 +/-7) ]
    Weekly mean pain intensity computed as the arithmetic mean of daily pain intensity values during the week prior to randomization and prior to each study visit. Daily pain intensity is measured on 0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") as reported in the Daily Symptom Diary.
  • Change in the weekly mean pain intensity after 9 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) ]
    Weekly mean pain intensity computed as the arithmetic mean of daily pain intensity values during the week prior to randomization and prior to each study visit. Daily pain intensity is measured on 0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") as reported in the Daily Symptom Diary.
  • Change in the weekly mean pain duration after 5 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 3 (study day 35 +/-7) ]
    Weekly mean pain duration computed as the arithmetic mean of daily pain duration values during the week prior to randomization and prior to each study visit. Daily pain duration is measured on 0-100 percentage scale where percent = "percent of waking day you had facial pain" as reported in the Daily Symptom Diary.
  • Change in the weekly mean pain duration after 9 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) ]
    Weekly mean pain duration computed as the arithmetic mean of daily pain duration values during the week prior to randomization and prior to each study visit. Daily pain duration is measured on 0-100 percentage scale where percent = "percent of waking day you had facial pain" as reported in the Daily Symptom Diary.
  • Change in the SF-McGill Pain Questionnaire total score after 5 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 3 (study day 35 +/-7) ]
    The SF-McGill Pain Questionnaire contains 15 descriptors (11 sensory, 4 affective) rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe." The item scores are summed to yield a total score ranging from 0 to 45.
  • Change in the SF-McGill Pain Questionnaire total score after 9 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) ]
    The SF-McGill Pain Questionnaire contains 15 descriptors (11 sensory, 4 affective) rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe."The item scores are summed to yield a total score ranging from 0 to 45.
  • Change in the SF-McGill Pain Questionnaire current facial pain intensity after 5 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 3 (study day 35 +/-7) ]
    Self-reported facial pain intensity at the visit scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable".
  • Change in the SF-McGill Pain Questionnaire current facial pain intensity after 9 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) ]
    Self-reported facial pain intensity at the visit scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable".
  • Change in the SF-McGill Pain Questionnaire weekly average facial pain intensity after 5 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 3 (study day 35 +/-7) ]
    Self-reported average facial pain intensity for the last week scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable".
  • Change in the SF-McGill Pain Questionnaire weekly average facial pain intensity after 9 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) ]
    Self-reported average facial pain intensity for the last week scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable".
  • Change in the SF-McGill Pain Questionnaire weekly average facial pain duration after 5 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 3 (study day 35 +/-7) ]
    Self-reported average facial pain duration for the last week scored on 0-100 percentage scale where percent = "percent of waking day you had facial pain".
  • Change in the SF-McGill Pain Questionnaire weekly average facial pain duration after 9 weeks of treatment [ Time Frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7) ]
    Self-reported average

    Original Secondary Outcome:

    • Change in the weekly mean pain intensity at 5 weeks [ Time Frame: Visit 1 and Visit 3 after 5 weeks of treatment ]
      Weekly mean pain intensity computed as the arithmetic mean of daily pain intensity values during the week prior to randomization and prior to each study visit. Daily pain intensity is measured on 0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") as reported in the Daily Symptom Diary.
    • Change in the weekly mean pain intensity at 9 weeks [ Time Frame: Visit 1 and Visit 4 after 9 weeks of treatment ]
      Weekly mean pain intensity computed as the arithmetic mean of daily pain intensity values during the week prior to randomization and prior to each study visit. Daily pain intensity is measured on 0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") as reported in the Daily Symptom Diary.
    • Change in the weekly mean pain duration at 5 weeks [ Time Frame: Visit 1 and Visit 3 after 5 weeks of treatment ]
      Weekly mean pain duration computed as the arithmetic mean of daily pain duration values during the week prior to randomization and prior to each study visit. Daily pain duration is measured on 0-100 percentage scale where percent = "percent of waking day you had facial pain" as reported in the Daily Symptom Diary.
    • Change in the weekly mean pain duration at 9 weeks [ Time Frame: Visit 1 and Visit 4 after 9 weeks of treatment ]
      Weekly mean pain duration computed as the arithmetic mean of daily pain duration values during the week prior to randomization and prior to each study visit. Daily pain duration is measured on 0-100 percentage scale where percent = "percent of waking day you had facial pain" as reported in the Daily Symptom Diary.
    • Change in the SF-McGill Pain Questionnaire total score at 5 weeks [ Time Frame: Visit 1 and Visit 3 after 5 weeks of treatment ]
      The SF-McGill Pain Questionnaire contains 15 descriptors (11 sensory, 4 affective) rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe." The item scores are summed to yield a total score ranging from 0 to 45.
    • Change in the SF-McGill Pain Questionnaire total score at 9 weeks [ Time Frame: Visit 1 and Visit 4 after 9 weeks of treatment ]
      The SF-McGill Pain Questionnaire contains 15 descriptors (11 sensory, 4 affective) rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe."The item scores are summed to yield a total score ranging from 0 to 45.
    • Change in the SF-McGill Pain Questionnaire current facial pain intensity at 5 weeks [ Time Frame: Visit 1 and Visit 3 after 5 weeks of treatment ]
      Self-reported facial pain intensity at the visit scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable".
    • Change in the SF-McGill Pain Questionnaire current facial pain intensity at 9 weeks [ Time Frame: Visit 1 and Visit 4 after 9 weeks of treatment ]
      Self-reported facial pain intensity at the visit scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable".
    • Change in the SF-McGill Pain Questionnaire weekly average facial pain intensity at 5 weeks [ Time Frame: Visit 1 and Visit 3 after 5 weeks of treatment ]
      Self-reported average facial pain intensity for the last week scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable".
    • Change in the SF-McGill Pain Questionnaire weekly average facial pain intensity at 9 weeks [ Time Frame: Visit 1 and Visit 4 after 9 weeks of treatment ]
      Self-reported average facial pain intensity for the last week scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable".
    • Change in the SF-McGill Pain Questionnaire weekly average facial pain duration at 5 weeks [ Time Frame: Visit 1 and Visit 3 after 5 weeks of treatment ]
      Self-reported average facial pain duration for the last week scored on 0-100 percentage scale where percent = "percent of waking day you had facial pain".
    • Change in the SF-McGill Pain Questionnaire weekly average facial pain duration at 9 weeks [ Time Frame: Visit 1 and Visit 4 after 9 weeks of treatment ]
      Self-reported average facial pain duration for the last week scored on 0-100 percentage scale where percent = "percent of waking day you had facial pain".
    • Change in the Graded Chronic Pain Scale (GCPS) Characteristic Pain Intensity (CPI) at 5 weeks

      Information By: University of North Carolina, Chapel Hill

      Dates:
      Date Received: May 4, 2015
      Date Started: August 2015
      Date Completion: September 2017
      Last Updated: December 1, 2016
      Last Verified: December 2016