Occipital Blocks for Acute Migraine

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Occipital Nerve Blocks for Acute Treatment of Pediatric Migraine

Conditions
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Chronic Migraine, Headache, Episodic Migraine

Intervention / Treatment
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* Drug: Lidocaine 4% Topical Application Cream [LMX 4]
* Drug: Lidocaine Hydrochloride 2 mg/mL Injectable Solution
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children / Adolescents: Males or females, ages 7 - 21, of any gender, race, or ethnicity Diagnosis of episodic or chronic migraine with acute headache flare lasting up to 3 months unresponsive to acute medications. Patients who report that acute medications were not used during this headache flare because those medications have been ineffective for several prior headache flares will be included Informed parental consent and subject assent Girls, who have reached menarche, must have a negative urine or serum pregnancy test Weight > 25kg Parents: Parents or guardians of children enrolled, who speak either English or Spanish, and provide parental/guardian permission (informed consent) for their own participation Subject (child) assent Exclusion Criteria: Children / Adolescents: Previous nerve block less than 3 months ago or more than 2 previous nerve blocks Allergy to local anesthetics Skull defect or break in the skin at the planned site of cream application or GON injection Any investigational drug use within 30 days prior to enrollment, or 90 days prior to enrollment for medications targeted at Calcitonin Gene-Related Peptide Pregnant or lactating females Parents/guardians or subjects who, in the opinion of the Investigator, may be non- compliant with study schedules or procedures Significant adverse event with prior injection or procedure New abnormalities on physical or neurological examination Newly reported red flags in headache history which prompt investigation for secondary headache Non-English and Non-Spanish speaking Non-English speaking with no Spanish interpreter available Parents: Parents or guardians of children enrolled, who do not speak either English or Spanish Parental/guardian permission and/or subject (child) assent has been declined Parents or guardians, who in the opinion of the investigator, may be non-compliant or unable to complete the questionnaires

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind greater occipital nerve injection of lidocaine versus saline after open-label lidocaine cream run-in
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Greater Occipital Nerve (GON) Block with Lidocaine<br>Subjects randomized to this arm receive 2 mL injection of lidocaine 2% over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. | Drug: Lidocaine 4% Topical Application Cream [LMX 4]<br>* Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve.<br>Drug: Lidocaine Hydrochloride 2 mg/mL Injectable Solution<br>* Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.<br>|
| Placebo Comparator: Greater Occipital Nerve (GON) Block with Saline<br>Subjects randomized to this arm receive 2 mL injection of preservative-free normal saline over the right and left greater occipital nerve at the baseline study visit. All subjects then complete daily headache-related questions through a Headache Diary and other assessments for 28 days. | Drug: Lidocaine 4% Topical Application Cream [LMX 4]<br>* Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve.<br>Drug: Normal Saline<br>* Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.<br>* Other names: 0.9% Sodium Chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Pain Intensity Scores | 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. A mean change of 2-points has been shown to be clinically relevant. | Pre-injection and 30 minutes Post-injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Disability | The PROMIS Pain Interference (Short Form) as well as the PedMIDAS 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. 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. Total scores correspond to one of four disability grades: 0 - 10 = little to no disability; 11-30 = mild disability; 31-50 = moderate disability; and > 50 = severe disability. | Baseline and Day 7 | 
| Percentage of Subjects with Pain Freedom | The measurement involves resolution of headache pain within 2 hours after injection and prior to any rescue medications. Data will be collected prospectively from subjects, via text, in an electronic headache diary. | 2 hours 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 2 hours and before any rescue medications. Data will be collected prospectively from subjects, via text, in an electronic headache diary. | 2 hours Post-injection | 
| Percentage of Subjects with Sustained Pain Freedom and Relief | The measurement involves being pain-free within 2-hours 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. | 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. | 24 hours Post-injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Chronic Migraine, Episodic Migraine, Headache, Nerve Block