Phase 2
N=200
Study of Orofacial Pain and PropRANOlol
Temporomandibular Disorders
Bottom Line
View on ClinicalTrials.gov: NCT02437383 ↗Enrolled (actual)
200
Serious AEs
2.5%
Results posted
May 2019
Primary outcome: Primary: Change in the Weekly Mean Pain Index After 9 Weeks of Treatment — -13.9; -12.1 units on a scale — p=0.414
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Propranolol ER (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of North Carolina, Chapel Hill
- Primary completion
- Apr 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in the Weekly Mean Pain Index After 9 Weeks of Treatment |
-13.9; -12.1 | 0.414 |
| SECONDARY Change in the Weekly Mean Pain Intensity After 9 Weeks of Treatment |
-17.1; -13.6 | — |
| SECONDARY Change in the Weekly Mean Pain Duration After 9 Weeks of Treatment |
-17.9; -16.6 | — |
| SECONDARY Change in the SF-McGill Pain Questionnaire Affective Component After 9 Weeks of Treatment |
-2.9; -3.1 | — |
| SECONDARY Change in the SF-McGill Pain Questionnaire Sensory Component After 9 Weeks of Treatment |
-1.9; -1.6 | — |
| SECONDARY Change in the SF-McGill Pain Questionnaire Present Facial Pain Intensity After 9 Weeks of Treatment |
-0.9; -0.7 | — |
| SECONDARY Change in the SF-McGill Pain Questionnaire Weekly Average Facial Pain Intensity After 9 Weeks of Treatment |
-18.2; -15.8 | — |
| SECONDARY Change in the SF-McGill Pain Questionnaire Weekly Average Facial Pain Duration After 9 Weeks of Treatment |
-23.6; -21.6 | — |
| SECONDARY Change in the SF-McGill Pain Questionnaire Weekly Fatigue After 9 Weeks of Treatment |
-12.0; -11.4 | — |
| SECONDARY Number of Participants Stratified Per Graded Chronic Pain Scale (GCPS) Grade After 9 Weeks of Treatment |
75; 69; 12; 18 | — |
| SECONDARY Change in the Jaw Functional Limitation Scale (JFLS) Global Score After 9 Weeks of Treatment |
-1.1; -0.8 | — |
| SECONDARY Change in the Headache Impact Test (HIT-6) Global Score After 9 Weeks of Treatment |
-5.1; -3.1 | — |
| SECONDARY Change in the Pittsburgh Sleep Quality Index (PSQI) Global Score After 9 Weeks of Treatment |
-0.7; -1.0 | — |
| SECONDARY Number of Participants Stratified Per Dichotomized Score From the Patient Global Impression of Change (PGIC) Scale After 9 Weeks of Treatment |
46; 60; 41; 27 | — |
| SECONDARY Change in the Perceived Stress Scale (PSS) Global Score After 9 Weeks of Treatment |
-2.6; -1.9 | — |
| SECONDARY Change in the Hospital Anxiety and Depression Scale (HADS) Depression Score After 9 Weeks of Treatment |
-1.0; -0.6 | — |
| SECONDARY Change in the Hospital Anxiety and Depression Scale (HADS) Anxiety Score After 9 Weeks of Treatment |
-1.3; -0.7 | — |
| SECONDARY Change in the Symptom Checklist 90-Revised (SCL-90R) Somatization Scale Score After 9 Weeks of Treatment |
-0.2; -0.2 | — |
| SECONDARY Change in the SF-12 Health Survey v2 (SF-12v2) Physical Component Summary (PCS) After 9 Weeks of Treatment |
1.2; 0.3 | — |
| SECONDARY Change in the SF-12 Health Survey v2 (SF-12v2) Mental Component Summary (MCS) After 9 Weeks of Treatment |
3.6; 2.8 | — |
| SECONDARY Change in Thermal Pain Threshold After 9 Weeks of Treatment |
1.3; 0.5 | — |
| SECONDARY Change in Thermal Pain Tolerance After 9 Weeks of Treatment |
0.5; 0.4 | — |
| SECONDARY Change in Pressure Pain Threshold at Temporalis Muscle After 9 Weeks of Treatment |
41.8; 38.4 | — |
| SECONDARY Change in Pressure Pain Threshold at Masseter Muscle After 9 Weeks of Treatment |
38.3; 29.3 | — |
| SECONDARY Change in Pressure Pain Threshold at Temporomandibular Joint After 9 Weeks of Treatment |
36.8; 25.3 | — |
| SECONDARY Change in Pressure Pain Threshold at Trapezius Muscle After 9 Weeks of Treatment |
64.1; 63.3 | — |
| SECONDARY Change in Pressure Pain Threshold at Lateral Epicondyle After 9 Weeks of Treatment |
41.4; 22.7 | — |
| SECONDARY Change in Pain-free Jaw Opening After 9 Weeks of Treatment |
4.5; 1.4 | — |
| SECONDARY Change in Maximum Unassisted Jaw Opening After 9 Weeks of Treatment |
-0.9; -1.2 | — |
| SECONDARY Change in Maximum Assisted Jaw Opening After 9 Weeks of Treatment |
-0.3; -0.8 | — |
| SECONDARY Change in Systolic Blood Pressure After 9 Weeks of Treatment |
-3.6; 1.3 | — |
| SECONDARY Change in Diastolic Blood Pressure After 9 Weeks of Treatment |
-3.3; 1.0 | — |
| SECONDARY Change in Heart Rate After 9 Weeks of Treatment |
-3.9; 1.5 | — |
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
Data sourced from ClinicalTrials.gov (NCT02437383). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.