Occipital Blocks for Acute Migraine

Episodic Migraine Clinical Trial

Official title:

Occipital Nerve Blocks for Acute Treatment of Pediatric Migraine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03526874
• Other study ID #: 18-014939
• Secondary ID: K23NS102521
• Status: Completed
• Phase: Phase 3
• Start date: April 3, 2019
• Est. completion date: March 10, 2023

Study information

• Verified date: April 2024
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: March 10, 2023
• Est. primary completion date: March 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Migraine, Headache
• Episodic Migraine
• Headache
• Migraine Disorders

Intervention

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

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Pre-injection (*Baseline*) and 30 minutes Post-injection
Primary	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".	Pre-injection and 30 minutes Post-injection
Secondary	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.	Baseline and Week 4
Secondary	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.	Baseline and Day 7
Secondary	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.	Baseline and Week 4
Secondary	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.	30 minutes Post-injection
Secondary	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.	30 minutes Post-injection
Secondary	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.	24 hours Post-injection
Secondary	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.	24 hours Post-injection
Secondary	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