Evaluate erenumab- aooe efficacy as a therapeutic approach, for the management of painful chronic temporomandibular disorders (TMD). The study will be a randomized, double blind, placebo-controlled trial comparing erenumab-aooe vs Placebo. A total of 60 patients (30 per each arm) aged 18-65 years old of either sex, and any race or ethnicity presenting chronic temporomandibular disorders (TMD), (meeting the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications of chronic TMD (myalgia +/- arthralgia) will be randomly assigned in a 1:1 parallel, double-blind clinical trial, to receive either erenumab-aooe or placebo. Participants will attend 6 clinic visits (Visit 0-Visit 5) over a period of 21 weeks (20 +/- 1 weeks). Changes in pain intensity and other pain outcomes related to TMD will be assessed. Blood samples will be collected, and participants will need to keep a daily symptom diary and answer some other questionnaires.
Chronic TMD is a considerable burden and affects significantly the quality of life of the sufferer. For some patients, TMD has a tendency to remit or improve pain symptomatology over time but for others, TMD have the potential to become chronic and to lead to persistent dysfunction. Different classes of medications from anti-inflammatories, muscle relaxants, anxiolytics, antidepressants, anticonvulsants and a β-blocker have indicated to be beneficial for some patients as well as in clinical studies, but tolerability and side effects may be present for some patients. Furthermore, the indications of these drugs are for other disorders, so it is unclear their mechanism of action in TMD pathophysiology. Currently there is no medication specifically indicated for the management of TMD based on its molecular pathophysiology. However, there is evidence showing that CGRP has a role in TMD pathophysiology. CGRP is a key molecule in migraine pathophysiology. Erenumab-aooe is the first antibody therapeutic targeting the CGRP and has shown efficacy, to be well tolerated and with a safety profile similar to placebo for the prevention of migraine. The scientific premise for this study is that inhibiting CGRP in chronic TMD will decrease pain, pain related outcomes and improve TMJ biomechanics (function) in a safe and well tolerated manner for this patient population. Potential participants will be pre-screened at the Brotman Facial Pain clinic and the Oral and Maxillofacial Surgery Clinic both at the University of Maryland, School of Dentistry or by telephone; those willing to participate will be scheduled for a screening and baseline visit (Visit 0). During this visit potential participants will be evaluated for eligibility (meeting the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications) of chronic TMD (myalgia +/- arthralgia) and written informed consent will be obtained. The screening and baseline procedures include medical history review, clinical examinations, tests and administration of questionnaires. After screening, eligible participants will start Visit 0/Day 0 which is the start of the baseline period with a duration of 28 days/4 weeks. Instructions will be given for the completion of a Daily Symptom Diary (DSD) and other questionnaires at home or online. Participants who show 80% compliance with the DSD and who meet the pain score (inclusion criteria) during the baseline period, will be randomly assigned to one of two groups either the investigational drug or placebo and will be scheduled for Visit 1. Visit 1 can occur within 7 days/1 week after the baseline period (+/- 7 days). The study drug is erenumab-aooe 70mg, SC injection. Participants will attend 6 clinic visits (Visit 0-Visit 5) over a period of 21 weeks (20 +/- 1 weeks) or 140 +/- 7 days. After randomization and on Visit 1 (Week 4/Day 28), the participant will receive the drug or placebo. This same treatment will be administered once a month for 3 months (3 cycles/12 weeks). It will be administered on Visit 1/Day 28/Week 4; Visit 2/Day 56/Week 8; and Visit 3/Day 84/week 12. On Visit 0 (baseline) and on Visit 1, Visit 2, Visit 3, Visit 4/Day 112/Week 16 and visit 5/Day 140/Week 20, visits will include review of compliance with inclusion criteria, medical history review, review and collection of any adverse event, clinical examinations, questionnaires, tests, blood sample collection on Baseline/Visit 0 and Visit 4; and instruction to complete the DSD and questionnaires.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
5
Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles.
Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles.
University of Maryland, School of Dentistry, Brotman Facial Pain Clinic
Baltimore, Maryland, United States
Change of >= 30% Reduction in the Monthly Average Pain Score From Baseline to Visit 4, Compared to Placebo.
Assessment of the efficacy of erenumab-aooe in the proportion of participants that achieve \>=30% reduction (Yes/no) in monthly average pain score from baseline to Visit 4 (the end of last monthly treatment cycle), compared to placebo. The daily pain intensity score will be measured on a 0-100 numeric rating scale (NRS) and reported in the Daily Symptom Diary (DSD). The monthly mean pain intensity score will be determined from baseline, Visit 1/Day 28/Week 4, Visit 2/Day 56/Week 8, Visit 3/Day 84/week 12 and Visit 4/Day 112/Week 16.
Time frame: From Visit 0 (Baseline phase/study day 0) to Visit 4 (study day 112)
Change of >= 50% Reduction in Monthly TMD Pain Days, Compared to Placebo.
Assessment of the efficacy of erenumab-aooe in the proportion of participants with at least a 50% reduction (Yes/No) in monthly TMD days from baseline to Visit 5 (follow up/final visit). Definition of TMD pain day: A TMD pain day was any calendar day in which the participant experienced pain, stiffness, soreness, tenderness, in the jaw or temple area or either side being brief or continuous; and/or pain with TMJ biomechanics (chewing, mouth opening or any jaw movement; and/or pain with jaw activities (yawning, kissing, talking); and/or pain with jaw habits (chewing gum, clenching, grinding).
Time frame: From Visit 0 (Baseline phase/study day 0) to Visit 5 (study day 140 +/- 7)
Change of >= 30% Reduction in the Monthly Average Pain Score Compared to Placebo From Baseline to Visit 5.
Assessment of the efficacy of erenumab-aooe in the proportion of participants who achieved a least 30% reduction in the monthly average daily pain score from baseline to Visit 5 (follow up and final study visit). The monthly mean pain intensity score will be determined from baseline, Visit 1/Day 28/Week 4, Visit 2/Day 56/Week 8, Visit 3/Day 84/week 12, Visit 4/Day 112/Week 16 and Visit 5/Day 140/Week 20.
Time frame: From Visit 0 (Baseline phase/study day 0) to Visit 5 (Study day 140 +/- 7)
Change in Pressure Pain Threshold (PPT) Measurement in Muscles of Mastication (Temporalis Muscle) Compared to Placebo From Baseline to Visit 5.
Assessments of pressure stimuli will be performed in the temporalis muscle and averaged to obtain a single pressure pain threshold value (kPa) per site. This assessment will be performed bilaterally in each temporalis muscle. A higher value means a better outcome.
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in Pressure Pain Threshold (PPT) Measurement in Muscles of Mastication (Masseter Muscle) Compared to Placebo From Baseline to Visit 5.
Assessments of pressure stimuli will be performed in the masseter muscle and averaged to obtain a single pressure pain threshold value (kPa) per site. This assessment will be performed bilaterally in each masseter muscle. A higher PPT value means a better outcome.
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in Pressure Pain Threshold (PPT) Measurement in Upper Trapezius Muscle Compared to Placebo From Baseline to Visit 5.
Assessments of pressure stimuli will be performed in the upper trapezius muscle and averaged to obtain a single pressure pain threshold value (kPa) per site (R/L side). This assessment will be performed bilaterally. A higher PPT value means a better outcome.
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in Pressure Pain Threshold (PPT) Measurement in the Temporomandibular Joint (TMJ) Compared to Placebo From Baseline to Visit 5.
Assessments of pressure stimuli will be performed in the TMJ and averaged to obtain a single pressure pain threshold value (kPa) per site. This assessment will be performed bilaterally. A higher PPT value means a better outcome.
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in Pressure Pain Threshold (PPT) Measurement at the Lateral Epicondyle Compared to Placebo From Baseline to Visit 5.
Assessments of pressure stimuli will be applied bilaterally in the right and left lateral epicondyles and averaged to obtain a single pressure pain threshold value (kPa) per site. A higher PPT value means a better outcome.
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in Maximum Unassisted Jaw Opening During Erenumab-aooe Treatment, After Treatment and Compared to Placebo.
Measured during TMD examination. A higher value means a better outcome
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in Maximum Pain Free Opening During Erenumab-aooe Treatment, After Treatment and Compared to Placebo.
Measured during TMD examination. A higher value means a better outcome
Time frame: Visit 0 (baseline/study day 0) to Visit 5/week 20 (Study day 140 +/- 7)
Change in Maximum Assisted/Active Opening During Erenumab-aooe Treatment, After Treatment and Compared to Placebo.
Measured during TMD examination. A higher value means a better outcome
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in the Jaw Functional Limitation Scale (JFLS) Global Score During Erenumab-aooe Treatment, After Treatment and Compared to Placebo.
The JFLS is a 20-item instrument that measures limitations across 3 domains related to TMJ biomechanics: masticatory function, jaw opening (vertical mobility), and verbal and emotional expression. A degree of limitation is rated on a 0-10 scale from 0 ("no limitation") to 10 ("severe limitation")
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in the Frequency of Oral Behaviors Evaluated by the Oral Behaviors Checklist (OBC) During Erenumab-aooe Treatment, After Treatment and Compared to Placebo.
The Oral Behaviors Checklist (OBC) evaluates parafunctional behaviors and generates a single scale representing the frequency of 21 activities such as clenching, chewing gum, and holding objects between teeth, yawning.
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in Graded Chronic Pain Scale (GCPS) Outcomes During Erenumab-aooe Treatment, After Treatment and Compared to Placebo.
The GCPS includes 7 items and assesses 2 dimensions of pain, pain intensity and pain-related disability. A higher grade means a worse outcome.
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in Impression of Overall Status Measured by the Patient Global Impression of Change (PGIC) During Erenumab-aooe Treatment, After Treatment and Compared to Placebo.
The PGIC measures change in participant's overall status on a scale ranging from 1 (very much improved) to 7 (very much worse).
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
Change in the Hospital Anxiety and Depression Scale (HADS). Anxiety and Depression Score Change During Erenumab-aooe Treatment, After Treatment and Compared to Placebo.
The HADS evaluates anxiety (7 items) and depression (7 items) with a 14-item instrument assessing symptoms on a 4-point scale rated from 0 "not at all" to 3 "very often indeed". Responses provide separate scores for anxiety and depression. A higher score means a worse outcome.
Time frame: Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7)
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