Migraine affects 10-28% of children and adolescents and yet 20-30% of patients are ineffectively treated with current oral and nasal options. Peripheral nerve blocks (PNBs), injections of local anesthetics over branches of the occipital and/or trigeminal nerves, have been associated with possible benefit for pediatric headaches in case series, and may be useful for both acute and preventive treatment of migraine for children who fail less invasive treatments. In fact, 80% of pediatric headache specialists reported using peripheral nerve blocks and carry low risk of serious side effects; however, peripheral nerve blocks have never been tested, formally, in a randomized pediatric trial. By applying a novel design that utilizes lidocaine cream as a run-in step, investigators intend to test the efficacy of the most commonly used peripheral nerve block, the greater occipital nerve (GON) block, as an acute treatment for pediatric migraine and determine whether lidocaine cream leads to successful blinding of the injection. The GON block is expected to prove effective in decreasing the pain of migraine, with lidocaine being superior to saline and lidocaine cream maintaining blinding.
There are two substantial hurdles that must be overcome in designing a trial to test the efficacy of PNBs: high placebo response rate and possible unblinding. In order to test the efficacy of this commonly used treatment for children and adolescents with difficult-to-treat headache, we need utilize a trial design which will address the high placebo response rate and the potential lack of blinding. About 194 children, recruited over a 3.5 year period at Children's Hospital of Philadelphia, will take part in this study. Participation will last about one month and involve one in-person study visit, and then completion of headache-related surveys, at home, for 28 days. Lidocaine cream lead-in will be used open-label for all subjects followed by double-blind randomized injections of active treatment (lidocaine) versus comparator (saline) in subjects who continue to have significant headache. To accomplish our secondary objectives, we will examine how expectation is affected by perceived treatment, and how expectations, measured in patients, parents, and providers, influence outcomes in pediatric and adolescent acute migraine.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
63
Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve.
Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.
Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS)
By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Numeric Rating Scale (NRS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. NRS scale is a 0 to 10 scale, with 0 meaning no pain and 10 meaning "the worse pain imaginable". A mean change of 2-points has been shown to be clinically relevant.
Time frame: Pre-injection (*Baseline*) and 30 minutes Post-injection
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS)
By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Visual Analog Scale (VAS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. VAS scale is a 0 to 100 visual scale, with 0 meaning no pain and 100 meaning "the worse pain imaginable".
Time frame: Pre-injection and 30 minutes Post-injection
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Sex
By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Numeric Rating Scale (NRS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By sex. NRS scale is a 0 to 10 scale, with 0 meaning no pain and 10 meaning "the worse pain imaginable". A mean change of 2-points has been shown to be clinically relevant.
Time frame: Pre-injection (*Baseline*) and 30 minutes Post-injection
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Sex
By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Visual Analog Scale (VAS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By sex. VAS scale is a 0 to 100 visual scale, with 0 meaning no pain and 100 meaning "the worse pain imaginable".
Time frame: Pre-injection and 30 minutes Post-injection
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Ethnicity
By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Numeric Rating Scale (NRS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By ethnicity. NRS scale is a 0 to 10 scale, with 0 meaning no pain and 10 meaning "the worse pain imaginable". A mean change of 2-points has been shown to be clinically relevant.
Time frame: Pre-injection (*Baseline*) and 30 minutes Post-injection
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Ethnicity
By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Visual Analog Scale (VAS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By ethnicity. VAS scale is a 0 to 100 visual scale, with 0 meaning no pain and 100 meaning "the worse pain imaginable".
Time frame: Pre-injection and 30 minutes Post-injection
Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Race
By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Numeric Rating Scale (NRS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By race. NRS scale is a 0 to 10 scale, with 0 meaning no pain and 10 meaning "the worse pain imaginable". A mean change of 2-points has been shown to be clinically relevant.
Time frame: Pre-injection (*Baseline*) and 30 minutes Post-injection
Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Race
By subtracting the 30 minutes post-injection score from the pre-injection score, measured on a Visual Analog Scale (VAS), the mean change, in the lidocaine versus saline groups, will be used as the primary outcome measure. By race. VAS scale is a 0 to 100 visual scale, with 0 meaning no pain and 100 meaning "the worse pain imaginable".
Time frame: score on a scale
Change From Baseline Disability
The PedMIDAS will assess changes in functional disability due to headache. The PedMIDAS is a validated 6-question scale that captures headache-related disability-across multiple domains of functioning including school, home, social, and recreational-for pediatric and adolescent aged patients over 3 months. The instrument measures the number of days in which subjects missed activities due to headache or migraine. The measure yields a total score by summing items ranging from 0 to 90 day. The higher the score the higher the disability. Change in total score (total at week 4 minus total at baseline) is reported.
Time frame: Baseline and Week 4
Change From Baseline Disability to Day 7
The Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (Short Form) will assess changes in functional disability due to headache. The PROMIS Pain Interference (Short Form) measures the self-reported consequences of pain on relevant aspects of the subject's life over the past seven days. A pain item pool was developed to yield scores on a T-score scale with a mean of 50 and standard deviation of 10. A higher PROMIS T-score represents more pain interference, a T-score of 60 is one standard deviation (SD) worse than average. By comparison, a pain interference T-score of 40 is one SD better than average.
Time frame: Baseline and Day 7
Change From Baseline Disability to Week 4
The PROMIS Pain Interference (Short Form) will assess changes in functional disability due to headache. The PROMIS Pain Interference (Short Form) measures the self-reported consequences of pain on relevant aspects of the subject's life over the past seven days. A pain item pool was developed to yield scores on a T-score scale with a mean of 50 and standard deviation of 10. A higher PROMIS T-score represents more pain interference, a T-score of 60 is one SD worse than average. By comparison, a pain interference T-score of 40 is one SD better than average.
Time frame: Baseline and Week 4
Percentage of Subjects With Pain Freedom
The measurement involves resolution of headache pain within 30 minutes after injection and prior to any rescue medications. Data will be collected prospectively from subjects, at the study visit.
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Time frame: 30 minutes Post-injection
Percentage of Subjects With Pain Relief or Headache Response
The measurement involves improvement in headache from "severe or moderate" to "none or mild" within 30 minutes and before any rescue medications. Data will be collected prospectively from subjects at the study visit.
Time frame: 30 minutes Post-injection
Percentage of Subjects With Sustained Pain Freedom
The measurement involves being pain-free within 30 minutes and lasting at least 24 hours, with no use of rescue medication and no relapse or recurrence. Data will be collected prospectively from subjects, via text, in an electronic headache diary.
Time frame: 24 hours Post-injection
Percentage of Subjects With Sustained Pain Relief
The measurement involves having pain-relief within 30 minutes and lasting at least 24 hours, with no use of rescue medication and no relapse or recurrence. Data will be collected prospectively from subjects, via text, in an electronic headache diary.
Time frame: 24 hours Post-injection
Percentage of Subjects With Freedom From All Symptoms of Migraine
The presence or absence of photophobia, phonophobia, and nausea will be collected from subjects prospectively, via text, in an electronic headache diary.
Time frame: 24 hours Post-injection