Temporomandibular Disorder
Conditions
Brief summary
The purpose of this proof of concept study is to evaluate the safety and efficacy of the off-label use of Aimovig® (EREN) in reducing Temporomandibular Disorder (TMD) pain compared to placebo.
Detailed description
This will be a 24-week, randomized, double-blinded, placebo-controlled, parallel group proof-of-concept study with two arms (active and placebo). The plan is to enroll 30 subjects. There will be a four-week screening period to identify subjects that meet the diagnostic criteria (DC/TMD) for myalgia, recommended by the International RDC/TMD Consortium Network and Orofacial Pain Special Interest Group. The Diagnostic Criteria for Temporomandibular Disorders Symptom Questionnaire and DC/TMD Examination Form will be used during Screening and Baseline visits to confirm the TMD diagnosis and determine whether subjects meet the inclusion/exclusion criteria. Subjects will attend a Screening visit followed by Baseline visit to randomize eligible subjects to active (EREN) or placebo (EREN-P). During the Baseline visit and Wks 4, 8, 12, and 16, subjects will receive treatment with either 140 mg of EREN or Placebo administered by subcutaneous injection. At Baseline and Wks 4, 8, 12, 16, 20, and 24 subjects will be instructed to complete the Brief Pain Inventory (BPI); PEG (Pain, Enjoyment, General Activity) Scale; pain mediation assessment; Patient Global Impression of Change (PGIC) (except for Baseline visit); Jaw Function Limitation Scale (JFLS); Patient Health Questionnaire (PHQ-4); and Somatic Symptom Scale (SSS-8). These visits will include review of continuance criteria and adverse event collection. At the Screening and Baseline visits the subjects will be instructed on how to use the PEG Scale and pain use assessment app, which will be downloaded on their smartphone, to provide a daily assessment of their pain intensity and interference with enjoyment and general activity (PEG) and their daily used of pain medications. Subjects who do not own a smartphone or are unwilling to use the app on a daily basis will only complete the PEG and pain medication assessment at the Baseline visit and all subsequent visits using the app onsite.
Interventions
DRUGPlacebo (EREN-P) s.c. administered every four weeks for a total of five treatments
Placebo (EREN-P) s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments
DRUGErenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments
Erenumab-aooe (EREN) 140 mg s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments
Sponsors
Amgen
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
Subjects eligible for inclusion in the study must meet all of the following criteria: 1. Signed the informed consent; 2. Have pain-related TMD myalgia assessed by history and clinical examination as established by the DC/TMD; 3. Age 18 years and younger than 60 years; 4. Have a good knowledge of the English language; 5. Able to understand and comply with the study requirements; 6. Have had TMD myalgia for 6 months or longer; and 7. If taking pain medications, the dose regimen must be stable for at least 4 weeks prior to the screening visit.
Exclusion criteria
Subjects meeting any of the following criteria are not eligible for inclusion: 1. Lacking stable bilateral posterior occlusion; 2. Currently uses a complete maxillary or mandibular prosthetic denture; 3. Currently pregnant or plan to become pregnant; 4. Breastfeeding or plan to breastfeed; 5. Allergic to erenumab-aooe or any of the ingredients in Aimovig® (acetate, polysorbate 80, and sucrose); 6. Allergic to rubber or latex; 7. Currently undergoing TMD treatment elsewhere; 8. Currently undergoing orthodontic treatment; 9. Currently included in other experimental protocols within the last 30 days before enrollment; 10. Having 11 or more headaches during the past 4 weeks; 11. Having received massage, acupuncture or physical therapy treatment of the head, neck or shoulders during the previous 3 months; 12. History of unstable or acute severe pain from another pain condition; 13. History of traumatic brain injury; 14. History of surgical treatment or recommended surgical treatment for TMD; 15. History of ongoing, unresolved disability litigation; 16. History of drug abuse; 17. History of moderate to severe sleep apnea requiring CPAP or oral mandibular repositioning appliance; 18. Anything that would place the subjects at increased risk or preclude the individual's full compliance with or completion of the study (e.g., medical condition, laboratory finding, physical exam finding logistical complication); and 19. History of previously receiving erenumab-aooe or other anti-CGRP therapies, including anti-CGRP and anti-CGRP receptor monoclonal antibodies and small molecule CGRP receptor antagonists (gepants). 20. History of chronic constipation and/or using medication associated with decreased gastrointestinal motility. 21. History of hypertension or risk factors for hypertension.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory (BPI) Pain Severity at 20 Weeks | 20 weeks. | Assessment of pain severity using the Brief Pain Inventory (BPI) 4-item pain severity scale at 20 weeks: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (secondary outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Daily Reported Pain Scores at 20 Weeks | 20 weeks | Assessment of pain using average of daily reported pain scores at 20 weeks; average of daily reported scores from days \> week 16 and \<= week 20. Pain scale: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome). |
| % of Days Taking Medication for Pain at 20 Weeks | 20 weeks | Assessment of pain using the % of days taking medication for pain at 20 weeks; percentage of days calculated from days \> week 16 and \<= week 20.Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome). |
| Pain Improvement Using the Patient Global Impression of Change in Pain at 20 Weeks | 20 weeks | Assessment of pain improvement using the patient global impression of change in pain scale at 20 weeks: 1 (Better) - 7 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome). |
| Jaw Function Limitation Scale (JFLS-8) at 20 Weeks | 20 weeks | Jaw Function Limitation Scale (JFLS-8) at 20 weeks: 0 (Better) - 10 (Worse).Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome). |
| Patient Health Questionnaire (PHQ-4) at 20 Weeks | 20 weeks | Depressive and Anxiety symptoms using Patient Health Questionnaire (PHQ-4) at 20 weeks: 0 (Better) - 12 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome). |
| Somatic Symptoms Scale (SSS-8) at 20 Weeks | 20 weeks | Assessment of somatic symptoms using the Somatic Symptoms Scale (SSS-8) at 20 weeks: 0 (Better) - 32 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome). |
| Brief Pain Inventory (BPI) Pain Severity at 24 Weeks | 24 weeks. | Assessment of pain severity using the Brief Pain Inventory (BPI) 4-item pain severity scale at 24 weeks: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (primary outcome). |
| Brief Pain Inventory (BPI) Pain Interference at 20 Weeks | 20 weeks | Assessment of pain interference using the Brief Pain Inventory (BPI) 7-item pain intensity scale at 20 weeks: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome). |
| Average Daily Reported Pain Scores at 24 Weeks | 24 weeks | Assessment of pain using average of daily reported pain scores at 24 weeks; average of daily reported scores from days \> week 20 and \<= week 24. Pain scale: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome). |
| % of Days Taking Medication for Pain at 24 Weeks | 24 weeks | Assessment of pain using the % of days taking medication for pain at 24 weeks; percentage of days calculated from days \> week 20 and \<= week 24. Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome). |
| Pain Improvement Using the Patient Global Impression of Change in Pain at 24 Weeks | 24 weeks | Assessment of pain improvement using the patient global impression of change in pain scale at 24 weeks: 1 (Better) - 7 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome). |
| Jaw Function Limitation Scale (JFLS-8) at 24 Weeks | 24 weeks | Jaw Function Limitation Scale (JFLS-8) at 24 weeks: 0 (Better) - 10 (Worse).Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome). |
| Patient Health Questionnaire (PHQ-4) at 24 Weeks | 24 weeks | Depressive and Anxiety symptoms using Patient Health Questionnaire (PHQ-4) at 24 weeks: 0 (Better) - 12 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome). |
| Somatic Symptoms Scale (SSS-8) at 24 Weeks | 24 weeks | Assessment of somatic symptoms using the Somatic Symptoms Scale (SSS-8) at 24 weeks: 0 (Better) - 32 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome). |
| Brief Pain Inventory (BPI) Pain Interference at 24 Weeks | 24 weeks | Assessment of pain interference using the Brief Pain Inventory (BPI) 7-item pain intensity scale at 24 weeks: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A Arm A: erenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments
Erenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments: Erenumab-aooe (EREN) 140 mg s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments | 15 |
| Arm B Arm B: placebo (EREN-P) s.c. administered every four weeks for a total of five treatments
Placebo (EREN-P) s.c. administered every four weeks for a total of five treatments: Placebo (EREN-P) s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 30 Participants |
| Age, Continuous | 34.9 years | 34.7 years | 34.8 years |
| Brief Pain Inventory (BPI) pain interference | 2.31 units on a scale STANDARD_DEVIATION 1.9 | 2.07 units on a scale STANDARD_DEVIATION 1.6 | 2.19 units on a scale STANDARD_DEVIATION 1.73 |
| Brief Pain Inventory (BPI) pain severity | 3.0 units on a scale STANDARD_DEVIATION 1.99 | 2.9 units on a scale STANDARD_DEVIATION 1.35 | 2.95 units on a scale STANDARD_DEVIATION 1.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 12 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Jaw Function Limitation Scale (JFLS-8) | 1.69 units on a scale STANDARD_DEVIATION 1.21 | 1.81 units on a scale STANDARD_DEVIATION 1.36 | 1.75 units on a scale STANDARD_DEVIATION 1.27 |
| Pain Score | 3.45 units on a scale STANDARD_DEVIATION 2.54 | 3.62 units on a scale STANDARD_DEVIATION 1.85 | 3.54 units on a scale STANDARD_DEVIATION 2.15 |
| Patient Health Questionnaire (PHQ-4) | 2.80 units on a scale STANDARD_DEVIATION 2.54 | 2.27 units on a scale STANDARD_DEVIATION 1.75 | 2.53 units on a scale STANDARD_DEVIATION 2.16 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 14 Participants | 28 Participants |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 13 Participants | 13 Participants | 26 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
| Somatic Symptoms Scale (SSS-8) | 6.80 units on a scale STANDARD_DEVIATION 4.81 | 8.60 units on a scale STANDARD_DEVIATION 4.15 | 7.70 units on a scale STANDARD_DEVIATION 4.51 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 9 / 15 | 7 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Brief Pain Inventory (BPI) Pain Severity at 20 Weeks
Assessment of pain severity using the Brief Pain Inventory (BPI) 4-item pain severity scale at 20 weeks: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (secondary outcome).
Time frame: 20 weeks.
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 12 and 2 additional Arm B subjects at week 20.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Brief Pain Inventory (BPI) Pain Severity at 20 Weeks | 1.72 score on a scale |
| Arm B | Brief Pain Inventory (BPI) Pain Severity at 20 Weeks | 1.42 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.56795% CI: [-0.76, 1.35]Mixed Models Analysis
Secondary
Average Daily Reported Pain Scores at 20 Weeks
Assessment of pain using average of daily reported pain scores at 20 weeks; average of daily reported scores from days \> week 16 and \<= week 20. Pain scale: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome).
Time frame: 20 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 4 Arm A subjects at wk 0, 1 Arm A at wk 4, 1 Arm A at wk 12, and 2 Arm B at wk 0.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Average Daily Reported Pain Scores at 20 Weeks | 1.92 score on a scale |
| Arm B | Average Daily Reported Pain Scores at 20 Weeks | 1.04 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.10595% CI: [-0.2, 1.96]Mixed Models Analysis
Secondary
Average Daily Reported Pain Scores at 24 Weeks
Assessment of pain using average of daily reported pain scores at 24 weeks; average of daily reported scores from days \> week 20 and \<= week 24. Pain scale: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome).
Time frame: 24 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 4 Arm A subjects at wk 0, 1 Arm A at wk 4, 1 Arm A at wk 12, and 2 Arm B at wk 0.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Average Daily Reported Pain Scores at 24 Weeks | 2.01 score on a scale |
| Arm B | Average Daily Reported Pain Scores at 24 Weeks | 1.49 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.45595% CI: [-0.88, 1.91]Mixed Models Analysis
Secondary
Brief Pain Inventory (BPI) Pain Interference at 20 Weeks
Assessment of pain interference using the Brief Pain Inventory (BPI) 7-item pain intensity scale at 20 weeks: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome).
Time frame: 20 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 12 and 1 additional Arm B subjects at week 20.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Brief Pain Inventory (BPI) Pain Interference at 20 Weeks | 1.11 score on a scale |
| Arm B | Brief Pain Inventory (BPI) Pain Interference at 20 Weeks | 0.96 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.77895% CI: [-0.91, 1.21]Mixed Models Analysis
Secondary
Brief Pain Inventory (BPI) Pain Interference at 24 Weeks
Assessment of pain interference using the Brief Pain Inventory (BPI) 7-item pain intensity scale at 24 weeks: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome).
Time frame: 24 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 12 and 1 additional Arm B subject at week 20.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Brief Pain Inventory (BPI) Pain Interference at 24 Weeks | 1.23 score on a scale |
| Arm B | Brief Pain Inventory (BPI) Pain Interference at 24 Weeks | 1.42 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.82295% CI: [-1.94, 1.56]Mixed Models Analysis
Secondary
Brief Pain Inventory (BPI) Pain Severity at 24 Weeks
Assessment of pain severity using the Brief Pain Inventory (BPI) 4-item pain severity scale at 24 weeks: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (primary outcome).
Time frame: 24 weeks.
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 12 and 2 additional Arm B subjects at week 20.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Brief Pain Inventory (BPI) Pain Severity at 24 Weeks | 1.99 score on a scale |
| Arm B | Brief Pain Inventory (BPI) Pain Severity at 24 Weeks | 1.51 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.47495% CI: [-0.87, 1.81]Mixed Models Analysis
Secondary
Jaw Function Limitation Scale (JFLS-8) at 20 Weeks
Jaw Function Limitation Scale (JFLS-8) at 20 weeks: 0 (Better) - 10 (Worse).Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome).
Time frame: 20 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 4 and 1 additional Arm A subject at week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Jaw Function Limitation Scale (JFLS-8) at 20 Weeks | 0.47 score on a scale |
| Arm B | Jaw Function Limitation Scale (JFLS-8) at 20 Weeks | 0.48 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.97295% CI: [-0.83, 0.8]Mixed Models Analysis
Secondary
Jaw Function Limitation Scale (JFLS-8) at 24 Weeks
Jaw Function Limitation Scale (JFLS-8) at 24 weeks: 0 (Better) - 10 (Worse).Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome).
Time frame: 24 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 4 and 1 additional Arm A subject at week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Jaw Function Limitation Scale (JFLS-8) at 24 Weeks | 0.92 score on a scale |
| Arm B | Jaw Function Limitation Scale (JFLS-8) at 24 Weeks | 1.16 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.61395% CI: [-1.18, 0.71]Mixed Models Analysis
Secondary
% of Days Taking Medication for Pain at 20 Weeks
Assessment of pain using the % of days taking medication for pain at 20 weeks; percentage of days calculated from days \> week 16 and \<= week 20.Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome).
Time frame: 20 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 4 and 1 additional Arm A subject at week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | % of Days Taking Medication for Pain at 20 Weeks | 23.0 percentage of days |
| Arm B | % of Days Taking Medication for Pain at 20 Weeks | 5.4 percentage of days |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.16395% CI: [-7.6, 42.7]Mixed Models Analysis
Secondary
% of Days Taking Medication for Pain at 24 Weeks
Assessment of pain using the % of days taking medication for pain at 24 weeks; percentage of days calculated from days \> week 20 and \<= week 24. Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome).
Time frame: 24 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 4 and 1 additional Arm A subject at week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | % of Days Taking Medication for Pain at 24 Weeks | 13.7 percentage of days |
| Arm B | % of Days Taking Medication for Pain at 24 Weeks | 6.6 percentage of days |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.46795% CI: [-12.8, 27]Mixed Models Analysis
Secondary
Pain Improvement Using the Patient Global Impression of Change in Pain at 20 Weeks
Assessment of pain improvement using the patient global impression of change in pain scale at 20 weeks: 1 (Better) - 7 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome).
Time frame: 20 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Pain Improvement Using the Patient Global Impression of Change in Pain at 20 Weeks | 3.50 score on a scale |
| Arm B | Pain Improvement Using the Patient Global Impression of Change in Pain at 20 Weeks | 3.55 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.9195% CI: [-1.13, 1.01]Mixed Models Analysis
Secondary
Pain Improvement Using the Patient Global Impression of Change in Pain at 24 Weeks
Assessment of pain improvement using the patient global impression of change in pain scale at 24 weeks: 1 (Better) - 7 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome).
Time frame: 24 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Pain Improvement Using the Patient Global Impression of Change in Pain at 24 Weeks | 3.70 score on a scale |
| Arm B | Pain Improvement Using the Patient Global Impression of Change in Pain at 24 Weeks | 3.56 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.75595% CI: [-0.79, 1.07]Mixed Models Analysis
Secondary
Patient Health Questionnaire (PHQ-4) at 20 Weeks
Depressive and Anxiety symptoms using Patient Health Questionnaire (PHQ-4) at 20 weeks: 0 (Better) - 12 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome).
Time frame: 20 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 12, 1 Arm B at week 4, and 1 Arm B at week 8.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Patient Health Questionnaire (PHQ-4) at 20 Weeks | 4.42 score on a scale |
| Arm B | Patient Health Questionnaire (PHQ-4) at 20 Weeks | 1.62 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.03795% CI: [0.18, 5.43]Mixed Models Analysis
Secondary
Patient Health Questionnaire (PHQ-4) at 24 Weeks
Depressive and Anxiety symptoms using Patient Health Questionnaire (PHQ-4) at 24 weeks: 0 (Better) - 12 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome).
Time frame: 24 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 12, 1 Arm B at week 4, and 1 Arm B at week 8.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Patient Health Questionnaire (PHQ-4) at 24 Weeks | 3.58 score on a scale |
| Arm B | Patient Health Questionnaire (PHQ-4) at 24 Weeks | 1.00 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.00395% CI: [0.94, 4.22]Mixed Models Analysis
Secondary
Somatic Symptoms Scale (SSS-8) at 20 Weeks
Assessment of somatic symptoms using the Somatic Symptoms Scale (SSS-8) at 20 weeks: 0 (Better) - 32 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (additional secondary outcome).
Time frame: 20 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Somatic Symptoms Scale (SSS-8) at 20 Weeks | 6.46 score on a scale |
| Arm B | Somatic Symptoms Scale (SSS-8) at 20 Weeks | 6.72 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.88595% CI: [-3.95, 3.43]Mixed Models Analysis
Secondary
Somatic Symptoms Scale (SSS-8) at 24 Weeks
Assessment of somatic symptoms using the Somatic Symptoms Scale (SSS-8) at 24 weeks: 0 (Better) - 32 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and end of treatment at 20 weeks (additional secondary outcome).
Time frame: 24 weeks
Population: Estimation done using mixed-model ANOVA which includes all available data from all time points for all subjects. This analysis reduces bias compared to an analysis at each time point that excludes subjects with missing data. All study subjects were included, even if they did not have data observed at the given time point. In addition to missing data shown in Participant Flow table, outcome-specific missing data for 1 additional Arm A subject at week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Arm A | Somatic Symptoms Scale (SSS-8) at 24 Weeks | 6.70 score on a scale |
| Arm B | Somatic Symptoms Scale (SSS-8) at 24 Weeks | 5.51 score on a scale |
Comparison: Based on two-sided paired t-tests and two-sample t-tests, all conducted at a 5% significance level, this pilot study had 80% power to detect effect sizes of 0.9 for changes over time within groups and effect sizes of 1.2 for differences between groups. To account for dropout, the study enrolled 15 patients per group, for a total of 30 patients.p-value: 0.53695% CI: [-2.7, 5.08]Mixed Models Analysis