Back to resultsOccipital Blocks for Acute Migraine
Primary Purpose
Chronic Migraine, Headache, Episodic Migraine
Status
Active
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Lidocaine 4% Topical Application Cream [LMX 4]
Lidocaine Hydrochloride 2 mg/mL Injectable Solution
Normal Saline
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Migraine, Headache focused on measuring Pain, Chronic Migraine, Episodic Migraine, Headache, Nerve Block
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
Sites / Locations
- Children's Hospital of Philadelphia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Greater Occipital Nerve (GON) Block with Lidocaine
Greater Occipital Nerve (GON) Block with Saline
Arm 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.
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.
Outcomes
Primary Outcome Measures
Mean Change in Pain Intensity Scores
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. A mean change of 2-points has been shown to be clinically relevant.
Secondary Outcome Measures
Change from Baseline Disability
The PROMIS Pain Interference (Short Form) as well as the PedMIDAS 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. 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. Total scores correspond to one of four disability grades: 0 - 10 = little to no disability; 11-30 = mild disability; 31-50 = moderate disability; and > 50 = severe disability.
Percentage of Subjects with Pain Freedom
The measurement involves resolution of headache pain within 2 hours after injection and prior to any rescue medications. Data will be collected prospectively from subjects, via text, in an electronic headache diary.
Percentage of Subjects with Pain Relief or Headache Response
The measurement involves improvement in headache from "severe or moderate" to "none or mild" within 2 hours and before any rescue medications. Data will be collected prospectively from subjects, via text, in an electronic headache diary.
Percentage of Subjects with Sustained Pain Freedom and Relief
The measurement involves being pain-free within 2-hours 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.
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.
Full Information
NCT ID
NCT03526874
First Posted
May 4, 2018
Last Updated
May 11, 2023
Sponsor
Children's Hospital of Philadelphia
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
1. Study Identification
Unique Protocol Identification Number
NCT03526874
Brief Title
Occipital Blocks for Acute Migraine
Official Title
Occipital Nerve Blocks for Acute Treatment of Pediatric Migraine
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 3, 2019 (Actual)
Primary Completion Date
March 10, 2023 (Actual)
Study Completion Date
September 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital of Philadelphia
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Migraine, Headache, Episodic Migraine
Keywords
Pain, Chronic Migraine, Episodic Migraine, Headache, Nerve Block
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind greater occipital nerve injection of lidocaine versus saline after open-label lidocaine cream run-in
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
116 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Greater Occipital Nerve (GON) Block with Lidocaine
Arm Type
Experimental
Arm 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.
Arm Title
Greater Occipital Nerve (GON) Block with Saline
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Lidocaine 4% Topical Application Cream [LMX 4]
Intervention Description
Run-in Step: All subjects receive 32 mg (4 cm ribbon of cream) applied, bilaterally, over greater occipital nerve.
Intervention Type
Drug
Intervention Name(s)
Lidocaine Hydrochloride 2 mg/mL Injectable Solution
Intervention Description
Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the active treatment.
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Other Intervention Name(s)
0.9% Sodium Chloride
Intervention Description
Subjects, who continue to experience headache pain after the run-in step, receive 2 (2 mL) injections of the comparator.
Primary Outcome Measure Information:
Title
Mean Change in Pain Intensity Scores
Description
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. A mean change of 2-points has been shown to be clinically relevant.
Time Frame
Pre-injection and 30 minutes Post-injection
Secondary Outcome Measure Information:
Title
Change from Baseline Disability
Description
The PROMIS Pain Interference (Short Form) as well as the PedMIDAS 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. 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. Total scores correspond to one of four disability grades: 0 - 10 = little to no disability; 11-30 = mild disability; 31-50 = moderate disability; and > 50 = severe disability.
Time Frame
Baseline and Day 7
Title
Percentage of Subjects with Pain Freedom
Description
The measurement involves resolution of headache pain within 2 hours after injection and prior to any rescue medications. Data will be collected prospectively from subjects, via text, in an electronic headache diary.
Time Frame
2 hours Post-injection
Title
Percentage of Subjects with Pain Relief or Headache Response
Description
The measurement involves improvement in headache from "severe or moderate" to "none or mild" within 2 hours and before any rescue medications. Data will be collected prospectively from subjects, via text, in an electronic headache diary.
Time Frame
2 hours Post-injection
Title
Percentage of Subjects with Sustained Pain Freedom and Relief
Description
The measurement involves being pain-free within 2-hours 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.
Time Frame
24 hours Post-injection
Title
Percentage of Subjects with Freedom from all symptoms of migraine
Description
The presence or absence of photophobia, phonophobia, and nausea will be collected from subjects prospectively, via text, in an electronic headache diary.
Time Frame
24 hours Post-injection
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christina L. Szperka, MD, MSCE
Organizational Affiliation
Children's Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
11739822
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.
Results Reference
background
PubMed Identifier
12837897
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.
Results Reference
background
PubMed Identifier
11279934
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.
Results Reference
background
PubMed Identifier
7950559
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.
Results Reference
background
PubMed Identifier
27731894
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.
Results Reference
background
PubMed Identifier
20554116
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.
Results Reference
background
PubMed Identifier
22384463
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.
Results Reference
background
Learn more about this trial
Occipital Blocks for Acute Migraine
We'll reach out to this number within 24 hrs