Migraine
Conditions
Keywords
chronic migraine, trigeminal neuralgia, migraine surgery, nerve decompression
Brief summary
To compare Botox-treated and Botox-untreated symptomatic tissues (defined as areas where the head hurts and the pain is felt) of chronic migraine (CM) patients using molecular studies.
Detailed description
Eligible patients for migraine surgery will be injected unilaterally with Botox prior to surgery. The effects of Botox on tissues will be evaluated.
Interventions
DRUGBotulinum toxin type A
Injection of Botulinum toxin type A in back of head
Sponsors
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-65 years * Diagnosis of Chronic Migraine consistent with International Classification of Headache Disorders (ICHD-III) criteria, with a history of bilateral headache pain and chronic tenderness in neck muscles * Patient is capable and willing to provide informed consent * Female subjects of child bearing potential must have a negative pregnancy test at enrollment and agree to remain abstinent or use acceptable methods of birth control (i.e., hormonal contraceptives, inrauterine device, diaphragm with spermicide, cervical cap or sponge, condoms or partner has had a vasectomy) for three months following injections of Botox * Patients referred by their primary Neurologist to the study surgeon and who are determined to be candidates for surgical decompression of extracranial sensory nerves. * Patient agrees to abstain from protocol-specific excluded medications beginning 14 days prior to the decompression surgery.
Exclusion criteria
* Patient has hypersensitivity reactions or other intolerance to Botox * Patient is pregnant or trying to become pregnant with the timeframe of the study. * Infection at proposed injection sites.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Gene Expression in Chronic Migraine Patients With OnabotulinumtoxinA Injection Treatment Versus No Treatment | One year | In this split-person study, patients with chronic bilateral occipital migraines scheduled for a study-unrelated migraine surgery (occipital nerve decompression surgery) had one side of their head undergo treatment with onabotulinumtoxinA injection, while the other side of the head underwent no treatment. Occipital periosteum tissue of both injected and uninjected sides was collected during migraine surgery for targeted transcriptome profiling and genome-wide epigenome analyses of inflammatory gene expression using NanoString of 594 genes (579 immunology-related genes involved in adaptive/innate response, lymphocyte activation, cytokine/chemokine/NF-kB/TNF/interferon signalling, neutrophils, macrophages, cytotoxic T, NK, Th1, B and dendritic cells, and 15 internal reference controls). The effects size (ratio of geometric means) of expression of gene expression was evaluated between injected and uninjected sides. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment With Onabotulinumtoxin A Injection One side of the occipital head of participants was treated with a total of 40 units of onabotulinumtoxin A injection 30 days prior to their scheduled, study-unrelated, nerve decompression surgery.
The specific sites injected were the following:
* 2 sites in the Occipitalis muscle (5 units each)
* 4 sites in the Cervical Paraspinal muscle group (5 units each)
* 2 sites in the Trapezius muscle (5 units each)
The selection of the side of the head to receive the injection treatment was random based on subject number. Participants assigned odd numbers were injected on the right, while participants with even numbers were injected on the left side. | 18 |
| Treatment With Onabotulinumtoxin A Injection One side of the occipital head of participants was treated with a total of 40 units of onabotulinumtoxin A injection 30 days prior to their scheduled, study-unrelated, nerve decompression surgery.
The specific sites injected were the following:
* 2 sites in the Occipitalis muscle (5 units each)
* 4 sites in the Cervical Paraspinal muscle group (5 units each)
* 2 sites in the Trapezius muscle (5 units each)
The selection of the side of the head to receive the injection treatment was random based on subject number. Participants assigned odd numbers were injected on the right, while participants with even numbers were injected on the left side. | 18 |
| No Treatment The other side of the occipital head of participants did not receive any injection intervention. | 18 |
| No Treatment The other side of the occipital head of participants did not receive any injection intervention. | 18 |
| Total | 72 |
Baseline characteristics
| Characteristic | Treatment With Onabotulinumtoxin A Injection | No Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 17 Participants | 34 Participants |
| Age, Continuous | 45 years STANDARD_DEVIATION 14 | 45 years STANDARD_DEVIATION 14 | 45 years STANDARD_DEVIATION 14 |
| Monthly migraine days | 19 days per month STANDARD_DEVIATION 10 | 19 days per month STANDARD_DEVIATION 10 | 19 days per month STANDARD_DEVIATION 10 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 18 Participants | 18 Participants | 18 Participants |
| Sex: Female, Male Female | 17 Participants | 17 Participants | 34 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 37 |
| other Total, other adverse events | 0 / 37 |
| serious Total, serious adverse events | 0 / 37 |
Outcome results
Primary
Inflammatory Gene Expression in Chronic Migraine Patients With OnabotulinumtoxinA Injection Treatment Versus No Treatment
In this split-person study, patients with chronic bilateral occipital migraines scheduled for a study-unrelated migraine surgery (occipital nerve decompression surgery) had one side of their head undergo treatment with onabotulinumtoxinA injection, while the other side of the head underwent no treatment. Occipital periosteum tissue of both injected and uninjected sides was collected during migraine surgery for targeted transcriptome profiling and genome-wide epigenome analyses of inflammatory gene expression using NanoString of 594 genes (579 immunology-related genes involved in adaptive/innate response, lymphocyte activation, cytokine/chemokine/NF-kB/TNF/interferon signalling, neutrophils, macrophages, cytotoxic T, NK, Th1, B and dendritic cells, and 15 internal reference controls). The effects size (ratio of geometric means) of expression of gene expression was evaluated between injected and uninjected sides.
Time frame: One year
Population: Among 37 total participants enrolled, 31 completed the study (received botox injection on one side, underwent surgery, had tissues collected from both sides). Among the 31, tissues of 18 patients fulfilled all criteria for inclusion for transcriptome analyses and data interpretation (data quality, background thresholding and normalization). The 13 patients who completed the study but were not included in the analysis are those whose transcriptome data quality failed inclusion criteria.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment With OnabotulinumtoxinA Injection | Inflammatory Gene Expression in Chronic Migraine Patients With OnabotulinumtoxinA Injection Treatment Versus No Treatment | 44.46156 mRNA units |
| No Treatment | Inflammatory Gene Expression in Chronic Migraine Patients With OnabotulinumtoxinA Injection Treatment Versus No Treatment | 68.74241 mRNA units |
p-value: <0.0001t-test, 2 sided