Occipital Blocks for Acute Migraine

Children's Hospital of Philadelphia (CHOP)

Status and phase: Completed; Phase 3

Conditions: Chronic Migraine, Headache; Episodic Migraine

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03526874

18-014939

K23NS102521 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 63 patients

Sex: All

Ages: 7 to 21 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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63 participants in 2 patient groups, including a placebo group

Greater Occipital Nerve (GON) Block with Lidocaine

Experimental group

Description:

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.

Treatment:

Drug: Lidocaine 4% Topical Application Cream [LMX 4]

Drug: Lidocaine Hydrochloride 2 mg/mL Injectable Solution

Greater Occipital Nerve (GON) Block with Saline

Placebo Comparator group

Description:

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.

Treatment:

Drug: Normal Saline

Drug: Lidocaine 4% Topical Application Cream [LMX 4]