Occipital Blocks for Acute Migraine

NCT03526874 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 18-014939K23NS102521
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Migraine, Headache; Episodic Migraine

Keywords

Pain; Chronic Migraine; Episodic Migraine; Headache; Nerve Block

Outcome Measures

Primary Outcomes (8)

• 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

• 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

• Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Sex

  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. By sex. 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

• Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Sex

  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. By sex. 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

• Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Ethnicity

  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. By ethnicity. 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

• Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Ethnicity

  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. By ethnicity. 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

• Mean Change in Pain Intensity Scores Measured by the Numeric Analog Scale (NRS) by Race

  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. By race. 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

• Mean Change in Pain Intensity Scores Measured by the Visual Analog Scale (VAS) by Race

  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. By race. VAS scale is a 0 to 100 visual scale, with 0 meaning no pain and 100 meaning "the worse pain imaginable".

  score on a scale

Secondary Outcomes (8)

• Change From Baseline Disability

  Baseline and Week 4

• Change From Baseline Disability to Day 7

  Baseline and Day 7

• Change From Baseline Disability to Week 4

  Baseline and Week 4

• Percentage of Subjects With Pain Freedom

  30 minutes Post-injection

• Percentage of Subjects With Pain Relief or Headache Response

  30 minutes Post-injection

Study Arms (2)

Greater Occipital Nerve (GON) Block with Lidocaine

EXPERIMENTAL

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]; Drug: Lidocaine Hydrochloride 2 mg/mL Injectable Solution

Greater Occipital Nerve (GON) Block with Saline

PLACEBO COMPARATOR

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]; Drug: Normal Saline

Interventions

Lidocaine 4% Topical Application Cream [LMX 4] DRUG

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

Greater Occipital Nerve (GON) Block with Lidocaine; Greater Occipital Nerve (GON) Block with Saline

Lidocaine Hydrochloride 2 mg/mL Injectable Solution 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 Lidocaine

Normal Saline DRUG

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

Also known as: 0.9% Sodium Chloride

Greater Occipital Nerve (GON) Block with Saline

Eligibility Criteria

• Age: 7 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (7)

• 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.

  PMID: 11739822 BACKGROUND

• 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.

  PMID: 12837897 BACKGROUND

• 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.

  PMID: 11279934 BACKGROUND

• 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.

  PMID: 7950559 BACKGROUND

• 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.

  PMID: 27731894 BACKGROUND

• 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.

  PMID: 20554116 BACKGROUND

• 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.

  PMID: 22384463 BACKGROUND

MeSH Terms

Conditions

Headache; Pain

Interventions

Lidocaine; Saline Solution; Sodium Chloride

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Christina Szperka
• Organization: Children's Hospital of Philadelphia

szperka@chop.edu

12155901719

Study Officials

• Christina L. Szperka, MD, MSCE

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind greater occipital nerve injection of lidocaine versus saline after open-label lidocaine cream run-in

Study Record Dates

• First Submitted: May 4, 2018
• First Posted: May 16, 2018
• Study Start: April 3, 2019
• Primary Completion: March 10, 2023
• Study Completion: March 10, 2023
• Last Updated: April 17, 2025
• Results First Posted: April 30, 2024

Record last verified: 2025-03

Locations

US (1)