Occipital Blocks for Acute Migraine

NCT ID: NCT03526874

Last Updated: 2025-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-03
• Study Completion Date: 2023-03-10

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.

Conditions

Chronic Migraine, Headache; Episodic Migraine

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Greater Occipital Nerve (GON) Block with Lidocaine

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.

Group Type: EXPERIMENTAL

Lidocaine 4% Topical Application Cream [LMX 4]

Intervention Type: DRUG

Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve.

Lidocaine Hydrochloride 2 mg/mL Injectable Solution

Intervention Type: DRUG

Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.

Greater Occipital Nerve (GON) Block with Saline

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.

Group Type: PLACEBO_COMPARATOR

Lidocaine 4% Topical Application Cream [LMX 4]

Intervention Type: DRUG

Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve.

Normal Saline

Intervention Type: DRUG

Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.

Interventions

Lidocaine 4% Topical Application Cream [LMX 4]

Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve.

Intervention Type: DRUG

Lidocaine Hydrochloride 2 mg/mL Injectable Solution

Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.

Intervention Type: DRUG

Normal Saline

Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.

Intervention Type: DRUG

Other Intervention Names

0.9% Sodium Chloride

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

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christina L. Szperka, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 11739822 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12837897 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11279934 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 7950559 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27731894 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20554116 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22384463 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

K23NS102521

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18-014939

Identifier Type: -

Identifier Source: org_study_id