Temporomandibular DisordersPhase 2SOPPRANONCT02437383
Study of Orofacial Pain and PropRANOlol
A Phase 2 study testing Propranolol ER in people with Temporomandibular Disorders, run by University of North Carolina, Chapel Hill at 3 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Temporomandibular Disorders
- What is being tested?
- Propranolol ER
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 3 sitesUnited States
- Study dates
- 20 Aug 2015to 25 Apr 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University at Buffalo School of Dental Medicine
Buffalo, New York, 14214
University of North Carolina at Chapel Hill School of Dentistry
Chapel Hill, North Carolina, 27599
University of Florida-Gainesville College of Dentistry
Gainesville, Florida, 32610-0404
About this study
Official title: Effect of COMT (Catecholamine-O-methyltransferase) Genetic Polymorphisms on Response to Propranolol Therapy in Temporomandibular Disorder
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).
Read more
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.
Read the detailed description
"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 augmented sympathetic responses to stressors. While increased β-adrenergic drive appears to heighten pain, β-adrenergic antagonists can reduce clinical pain and/or nociceptive sensitivity. A recent study of a single infusion of propranolol in TMD and fibromyalgia patients revealed short-term improvement in clinical pain ratings. The antagonist pindolol was similarly efficacious in alleviating cardinal symptoms of fibromyalgia pain. In addition, intramuscular injections of low-dose propranolol in rats reduced inflammatory pain associated with carrageen-induced inflammation of the gastrocnemius muscle.
The study hypothesis is that therapy with the nonselective β-adrenergic receptor antagonist propranolol extended-release capsules (FDA approved to treat many cardiac conditions, tremor, migraine, and pheochromocytoma) will provide efficacious and safe treatment for painful TMD. It has well-studied pharmacodynamic, pharmacokinetic, and side-effect profiles. Peak blood level occurs at approximately 6 hrs, and the plasma half-life is approximately 10 hrs. The primary objective is to investigate the efficacy of propranolol compared with placebo over 9 weeks to reduce pain in patients with TMD. Secondary objectives are to: investigate by treatment group whether reduction in pain varies according to polymorphisms in the COMT gene coding region; and investigate the effect of propranolol compared with placebo to affect pain sensitivity, physical and emotional function, adverse effects, and use of rescue medications. Exploratory objectives are to: investigate gene-by-treatment group interaction to determine the effect of propranolol on reduction in the pain index according to polymorphisms in the COMT, beta-2 adrenergic receptor (ADRβ2), and beta-3 adrenergic receptor (ADRβ3) genetic coding regions.
- Conditions
- Temporomandibular Disorders
- Being tested
- Propranolol ER, Placebo
- Medical subject headings
- Temporomandibular Joint Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Propranolol ERDrug
Also called Inderal (long-acting)
Capsules given orally according to schedule at Visit 1, Visit 2, Visit 3, and Visit 4.
PlaceboDrug
Also called Sugar pill
Gelatin capsules with a microcrystalline cellulose filler manufactured to mimic propranolol ER 60 mg capsules
| Study group | Role | What they receive |
|---|---|---|
| Propranolol ER | Active comparator | Propranolol hydrochloride extended release (ER) capsules; 60 mg (Visit 1 and Visit 4); 120 mg (Visit 2 and Visit 3) given orally as: 60 mg once/day (Visit 1 and Visit 4) and 60 mg twice/day (Visit 2 and Visit 3). Receives: Drug: Propranolol ER |
| Placebo | Placebo comparator | Capsules, identical in appearance to active comparator (propranolol), to be administered orally in exactly the same manner as propranolol at Visit 1 (once/day), Visit 2 (twice/day), Visit 3 (twice/day), and Visit 4 (once/day). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the Weekly Mean Pain Index 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 and divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Secondary outcomes (32)
Change in the Weekly Mean Pain Intensity 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. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Weekly Mean Pain Duration 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. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-McGill Pain Questionnaire Affective Component After 9 Weeks of Treatment
The SF-McGill Pain Questionnaire contains 4 affective descriptors 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 12. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-McGill Pain Questionnaire Sensory Component After 9 Weeks of Treatment
The SF-McGill Pain Questionnaire contains 11 sensory descriptors 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 33. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-McGill Pain Questionnaire Present Facial Pain Intensity After 9 Weeks of Treatment
Self-reported present intensity of facial pain at the moment of assessment scored on a descriptive scale where 1 = "no pain' and 6 = "excruciating pain." A higher score means worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-McGill Pain Questionnaire Weekly Average Facial Pain Intensity 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". A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-McGill Pain Questionnaire Weekly Average Facial Pain Duration 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". A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-McGill Pain Questionnaire Weekly Fatigue After 9 Weeks of Treatment
Self-reported average fatigue for the last week scored on 0-100 numerical rating scale where 0 = "no fatigue" and 100 = "the greatest imaginable." A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Number of Participants Stratified Per Graded Chronic Pain Scale (GCPS) Grade After 9 Weeks of Treatment
Individuals were classified into 6 chronic pain grades: 0 = no pain; I = low pain intensity and low pain-related disability; IIa = high pain intensity and low pain-related disability; IIb = high pain intensity and high activity interference; III = moderate pain-related disability; and IV = severe pain-related disability. For analyses, this variable was dichotomized: grades 0-IIa were combined in one category and all higher grades in another. A higher grade means a worse outcome.
Measured: Visit 4 (study day 63 +/-7)
Change in the Jaw Functional Limitation Scale (JFLS) Global Score After 9 Weeks of Treatment
The JFLS contains 20 items that measure limitations across mastication, vertical jaw mobility, and verbal/emotional expression rated on a 0-10 scale where 0 = "no limitation" and 10 = "severe limitation." The Global Score is computed as the mean response for all items and ranges from 0 to 10. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Headache Impact Test (HIT-6) Global Score After 9 Weeks of Treatment
The HIT-6 contains 6 items and assesses headache-related disability by the frequency of daily activity limitations ranging from "never" to "always." The 6 item scores are summed to yield a global score ranging from 36 to 78. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Pittsburgh Sleep Quality Index (PSQI) Global Score After 9 Weeks of Treatment
The PSQI has 19 items grouped into 7 component scores, each weighted equally on a 0-3 scale, The 7 component scores are summed to yield a global PSQI score, which has a range of 0-21. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Number of Participants Stratified Per Dichotomized Score From the Patient Global Impression of Change (PGIC) Scale After 9 Weeks of Treatment
The PGIC scale assesses patient overall change in the severity of illness following treatment. Participants rate how they feel now compared with how they felt before receiving study drug on a 7-point scale where 0 = "No change or condition has got worse" and 6 = "A great deal better." A higher score means a better outcome. For analyses, this variable was dichotomized: scores from 0 to 3 were combined in one category of "No" (no significant improvement) and scores from 4 to 6 were combined in another category of "Yes" (significant improvement with the study treatment).
Measured: Visit 4 (study day 63 +/-7)
Change in the Perceived Stress Scale (PSS) Global Score After 9 Weeks of Treatment
The PSS assesses the frequency of 14 sources of stress on a scale from 0 = "never" to 4 = "very often." The item scores are summed to yield a global score ranging from 0 to 56. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Hospital Anxiety and Depression Scale (HADS) Depression Score After 9 Weeks of Treatment
The HADS is a 14-item assessment of anxiety (7 items) and depression (7 items) using the relative frequency of symptoms over the past week, rated on a 4-point scale ranging from 0 = "not at all" to 3 = "very often indeed". Responses are summed to provide separate scores for anxiety and depression with a range from 0 to 21. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Hospital Anxiety and Depression Scale (HADS) Anxiety Score After 9 Weeks of Treatment
The HADS is a 14-item assessment of anxiety (7 items) and depression (7 items) using the relative frequency of symptoms over the past week, rated on a 4-point scale ranging from 0 = "not at all" to 3 = "very often indeed". Responses are summed to provide separate scores for anxiety and depression with a range from 0 to 21. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Symptom Checklist 90-Revised (SCL-90R) Somatization Scale Score After 9 Weeks of Treatment
The SCL-90R Somatization Scale is a 12-item assessment of somatic symptom distress over the past 7 days rated from 0 = "not at all" to 4 = "extremely." The scale score is computed as the mean for all items. The score range is from 0 to 4. A higher score means a worse outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-12 Health Survey v2 (SF-12v2) Physical Component Summary (PCS) After 9 Weeks of Treatment
The SF-12v2 contains 7 questions assessing 8 domains of functioning and well-being rated from: "excellent" to "poor" (for general health); "yes, limited a lot" to "no, not limited at all" (for functional level); and "all of the time" to "none of the time" (for emotional state). These 8 domains can be further summarized into a physical component summary (PCS) and a mental component summary (MCS). summary (MCS). The range for each component is 0-100 and a higher score means a better outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-12 Health Survey v2 (SF-12v2) Mental Component Summary (MCS) After 9 Weeks of Treatment
The SF-12v2 contains 7 questions assessing 8 domains of functioning and well-being rated from: "excellent" to "poor" (for general health); "yes, limited a lot" to "no, not limited at all" (for functional level); and "all of the time" to "none of the time" (for emotional state). These 8 domains can be further summarized into a physical component summary (PCS) and a mental component summary (MCS). The range for each component is 0-100 and a higher score means a better outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Thermal Pain Threshold After 9 Weeks of Treatment
Temperature values, measured in degrees Celsius, from 4 examiner-applied contact heat stimuli will be averaged to measure the experimental thermal pain threshold (temperature at which pain is first perceived). The range was 32-50 degrees Celsius and a higher value means a better outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Thermal Pain Tolerance After 9 Weeks of Treatment
Temperature values, measured in degrees Celsius, from 4 examiner-applied contact heat stimuli will be averaged to measure the experimental thermal pain tolerance (temperature at which pain can no longer be tolerated). The range was 32-50 degrees Celsius and a higher value means a better outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Pressure Pain Threshold at Temporalis Muscle After 9 Weeks of Treatment
Pressure values, measured in kilopascals (kPa), from up to 5 experimental pressure stimuli, bilaterally applied to the area of temporalis muscle, are averaged to obtain a single pressure pain threshold value per anatomical site. The range is 0-500 kPa and a higher value means a better outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Pressure Pain Threshold at Masseter Muscle After 9 Weeks of Treatment
Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of masseter muscle, will be averaged to obtain a single pressure pain threshold value per anatomical site.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/- 7)
Change in Pressure Pain Threshold at Temporomandibular Joint After 9 Weeks of Treatment
Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of temporomandibular joint, will be averaged to obtain a single pressure pain threshold value per anatomical site.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Pressure Pain Threshold at Trapezius Muscle After 9 Weeks of Treatment
Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of trapezius muscle, will be averaged to obtain a single pressure pain threshold value per anatomical site.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Pressure Pain Threshold at Lateral Epicondyle After 9 Weeks of Treatment
Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of lateral epicondyle, will be averaged to obtain a single pressure pain threshold value per anatomical site.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Pain-free Jaw Opening After 9 Weeks of Treatment
Measured at TMD exam. A higher value means a better outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Maximum Unassisted Jaw Opening After 9 Weeks of Treatment
Measured at TMD exam. A higher value means a better outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Maximum Assisted Jaw Opening After 9 Weeks of Treatment
Measured at TMD exam. A higher value means a better outcome.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Systolic Blood Pressure After 9 Weeks of Treatment
Average of 3 repeated measures taken with a 2-minute interval.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Diastolic Blood Pressure After 9 Weeks of Treatment
Average of 3 repeated measures taken with a 2-minute interval.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Heart Rate After 9 Weeks of Treatment
Average of 3 repeated measures taken with a 2-minute interval.
Measured: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2015 (estimated)
- Study start20 Aug 2015
- Primary completion4 Apr 2018
- Study completion25 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Temporomandibular DisordersStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- University of Florida, Rho, Inc., National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR), State University of New York at Buffalo
- Responsible party
- Sponsor
- Investigators
- Inna E. Tchivileva, MD, Principal investigator, University of North Carolina, Chapel HillRoger B. Fillingim, PhD, Principal investigator, University of Florida-Gainesville College of DentistryRichard Ohrbach, DDS, PhD, Principal investigator, University at Buffalo School of Dental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02437383
- Sponsor's protocol ID
- 14-2526
- Other IDs
- 1U01DE024169-01, 14-067-E
- Acronym
- SOPPRANO
- Status last verified
- Apr 2018
- First submitted
- 4 May 2015
- Last updated
- 21 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 20216107Gursoy 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.
PubMed 12739038Diatchenko 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.
PubMed 15537663Tchivileva 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.
PubMed 34022805Tchivileva 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.
PubMed 33560875Slade 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.
PubMed 33030089Tchivileva 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.
PubMed 32701836Sanders 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.
PubMed 32297945
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of COMT (Catecholamine-O-methyltransferase) Genetic Polymorphisms on Response to Propranolol Therapy in Temporomandibular Disorder
- ClinicalTrials.gov ID
- NCT02437383
- Acronym / sponsor ID
- SOPPRANO / 14-2526
- Conditions
- Temporomandibular Disorders
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- University of Florida, Rho, Inc., National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR), State University of New York at Buffalo
- Study start
- 20 Aug 2015 (actual)
- Primary completion
- 4 Apr 2018 (actual)
- Study completion
- 25 Apr 2018 (actual)
- First posted
- 7 May 2015 (estimated)
- Results
- Posted 21 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
"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 augmented sympathetic responses to stressors. While increased β-adrenergic drive appears to heighten pain, β-adrenergic antagonists can reduce clinical pain and/or nociceptive sensitivity. A recent study of a single infusion of propranolol in TMD and fibromyalgia patients revealed short-term improvement in clinical pain ratings. The antagonist pindolol was similarly efficacious in alleviating cardinal symptoms of fibromyalgia pain. In addition, intramuscular injections of low-dose propranolol in rats reduced inflammatory pain associated with carrageen-induced inflammation of the gastrocnemius muscle.
The study hypothesis is that therapy with the nonselective β-adrenergic receptor antagonist propranolol extended-release capsules (FDA approved to treat many cardiac conditions, tremor, migraine, and pheochromocytoma) will provide efficacious and safe treatment for painful TMD. It has well-studied pharmacodynamic, pharmacokinetic, and side-effect profiles. Peak blood level occurs at approximately 6 hrs, and the plasma half-life is approximately 10 hrs. The primary objective is to investigate the efficacy of propranolol compared with placebo over 9 weeks to reduce pain in patients with TMD. Secondary objectives are to: investigate by treatment group whether reduction in pain varies according to polymorphisms in the COMT gene coding region; and investigate the effect of propranolol compared with placebo to affect pain sensitivity, physical and emotional function, adverse effects, and use of rescue medications. Exploratory objectives are to: investigate gene-by-treatment group interaction to determine the effect of propranolol on reduction in the pain index according to polymorphisms in the COMT, beta-2 adrenergic receptor (ADRβ2), and beta-3 adrenergic receptor (ADRβ3) genetic coding regions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Propranolol ER | Active comparator | Drug: Propranolol ERPropranolol hydrochloride extended release (ER) capsules; 60 mg (Visit 1 and Visit 4); 120 mg (Visit 2 and Visit 3) given orally as: 60 mg once/day (Visit 1 and Visit 4) and 60 mg twice/day (Visit 2 and Visit 3). |
| Placebo | Placebo comparator | Drug: PlaceboCapsules, identical in appearance to active comparator (propranolol), to be administered orally in exactly the same manner as propranolol at Visit 1 (once/day), Visit 2 (twice/day), Visit 3 (twice/day), and Visit 4 (once/day). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Propranolol ERAlso: Inderal (long-acting)Capsules given orally according to schedule at Visit 1, Visit 2, Visit 3, and Visit 4. | Drug | Propranolol ER |
| PlaceboAlso: Sugar pillGelatin capsules with a microcrystalline cellulose filler manufactured to mimic propranolol ER 60 mg capsules | Drug | Placebo |
Primary outcome
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 and divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome.
32 secondary outcomes
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)
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)
Change in the SF-McGill Pain Questionnaire Affective Component After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-McGill Pain Questionnaire Sensory Component After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-McGill Pain Questionnaire Present Facial Pain Intensity After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
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)
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)
Change in the SF-McGill Pain Questionnaire Weekly Fatigue After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Number of Participants Stratified Per Graded Chronic Pain Scale (GCPS) Grade After 9 Weeks of Treatment
Time frame: Visit 4 (study day 63 +/-7)
Change in the Jaw Functional Limitation Scale (JFLS) Global Score After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Headache Impact Test (HIT-6) Global Score After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Pittsburgh Sleep Quality Index (PSQI) Global Score After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Number of Participants Stratified Per Dichotomized Score From the Patient Global Impression of Change (PGIC) Scale After 9 Weeks of Treatment
Time frame: Visit 4 (study day 63 +/-7)
Change in the Perceived Stress Scale (PSS) Global Score After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Hospital Anxiety and Depression Scale (HADS) Depression Score After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Hospital Anxiety and Depression Scale (HADS) Anxiety Score After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the Symptom Checklist 90-Revised (SCL-90R) Somatization Scale Score After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-12 Health Survey v2 (SF-12v2) Physical Component Summary (PCS) After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in the SF-12 Health Survey v2 (SF-12v2) Mental Component Summary (MCS) After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Thermal Pain Threshold After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Thermal Pain Tolerance After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Pressure Pain Threshold at Temporalis Muscle After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Pressure Pain Threshold at Masseter Muscle After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/- 7)
Change in Pressure Pain Threshold at Temporomandibular Joint After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Pressure Pain Threshold at Trapezius Muscle After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Pressure Pain Threshold at Lateral Epicondyle After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Pain-free Jaw Opening After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Maximum Unassisted Jaw Opening After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Maximum Assisted Jaw Opening After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Systolic Blood Pressure After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Diastolic Blood Pressure After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Change in Heart Rate After 9 Weeks of Treatment
Time frame: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20216107Tchivileva 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: PubMed 12739038Gursoy 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: PubMed 15537663Diatchenko 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.
- Derived from this study: PubMed 34022805Tchivileva 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.
- Derived from this study: PubMed 33560875Tchivileva 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.
- Derived from this study: PubMed 33030089Slade 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.
- Derived from this study: PubMed 32701836Tchivileva 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.
- Derived from this study: PubMed 32297945Sanders 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Inna E. Tchivileva, MD principal investigator
University of North Carolina, Chapel Hill
Roger B. Fillingim, PhD principal investigator
University of Florida-Gainesville College of Dentistry
Richard Ohrbach, DDS, PhD principal investigator
University at Buffalo School of Dental Medicine
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Propranolol ER in people with Temporomandibular Disorders, run by University of North Carolina, Chapel Hill at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02437383, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2019; AzTrials last refreshed its copy on 6 Nov 2026.