Clinical trial NCT03526874: Occipital Blocks for Acute Migraine
Official title: Occipital Nerve Blocks for Acute Treatment of Pediatric Migraine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Migraine, Headache
Episodic Migraine
Keywords: Pain
Chronic Migraine
Episodic Migraine
Headache
Nerve Block
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2018-05-16
Enrollment: 63
Sex: ALL
Minimum age (years): 7
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind greater occipital nerve injection of lidocaine versus saline after open-label lidocaine cream run-in
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS)
timeFrame: Pre-injection (*Baseline*) and 30 minutes Post-injection
measure: Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS)
timeFrame: Pre-injection and 30 minutes Post-injection
measure: Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Sex
timeFrame: Pre-injection (*Baseline*) and 30 minutes Post-injection
measure: Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Sex
timeFrame: Pre-injection and 30 minutes Post-injection
measure: Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Ethnicity
timeFrame: Pre-injection (*Baseline*) and 30 minutes Post-injection
measure: Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Ethnicity
timeFrame: Pre-injection and 30 minutes Post-injection
measure: Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Race
timeFrame: Pre-injection (*Baseline*) and 30 minutes Post-injection
measure: Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Race
timeFrame: score on a scale
Secondary outcomes:
measure: Change From Baseline Disability
timeFrame: Baseline and Week 4
measure: Change From Baseline Disability to Day 7
timeFrame: Baseline and Day 7
measure: Change From Baseline Disability to Week 4
timeFrame: Baseline and Week 4
measure: Percentage of Subjects With Pain Freedom
timeFrame: 30 minutes Post-injection
measure: Percentage of Subjects With Pain Relief or Headache Response
timeFrame: 30 minutes Post-injection
measure: Percentage of Subjects With Sustained Pain Freedom
timeFrame: 24 hours Post-injection
measure: Percentage of Subjects With Sustained Pain Relief
timeFrame: 24 hours Post-injection
measure: Percentage of Subjects With Freedom From All Symptoms of Migraine
timeFrame: 24 hours Post-injection
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania
name: Christina L. Szperka, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hershey AD, Powers SW, Vockell AL, LeCates S, Kabbouche MA, Maynard MK. PedMIDAS: development of a questionnaire to assess disability of migraines in children. Neurology. 2001 Dec 11;57(11):2034-9. doi: 10.1212/wnl.57.11.2034.
citation: Powers SW, Patton SR, Hommel KA, Hershey AD. Quality of life in childhood migraines: clinical impact and comparison to other chronic illnesses. Pediatrics. 2003 Jul;112(1 Pt 1):e1-5. doi: 10.1542/peds.112.1.e1.
citation: Split W, Neuman W. Epidemiology of migraine among students from randomly selected secondary schools in Lodz. Headache. 1999 Jul-Aug;39(7):494-501. doi: 10.1046/j.1526-4610.1999.3907494.x.
citation: Abu-Arefeh I, Russell G. Prevalence of headache and migraine in schoolchildren. BMJ. 1994 Sep 24;309(6957):765-9. doi: 10.1136/bmj.309.6957.765.
citation: Szperka CL, Gelfand AA, Hershey AD. Patterns of Use of Peripheral Nerve Blocks and Trigger Point Injections for Pediatric Headache: Results of a Survey of the American Headache Society Pediatric and Adolescent Section. Headache. 2016 Nov;56(10):1597-1607. doi: 10.1111/head.12939. Epub 2016 Oct 12.
citation: Amtmann D, Cook KF, Jensen MP, Chen WH, Choi S, Revicki D, Cella D, Rothrock N, Keefe F, Callahan L, Lai JS. Development of a PROMIS item bank to measure pain interference. Pain. 2010 Jul;150(1):173-182. doi: 10.1016/j.pain.2010.04.025.
citation: Tfelt-Hansen P, Pascual J, Ramadan N, Dahlof C, D'Amico D, Diener HC, Hansen JM, Lanteri-Minet M, Loder E, McCrory D, Plancade S, Schwedt T; International Headache Society Clinical Trials Subcommittee. Guidelines for controlled trials of drugs in migraine: third edition. A guide for investigators. Cephalalgia. 2012 Jan;32(1):6-38. doi: 10.1177/0333102411417901. No abstract available.