Trial Outcomes & Findings for (Botox) Mechanisms of Action in Altering the Molecular Environment in Which Pain Fibers Exist (NCT NCT03381261)
NCT ID: NCT03381261
Last Updated: 2025-03-24
Results Overview
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.
COMPLETED
PHASE4
37 participants
One year
2025-03-24
Participant Flow
Unit of analysis: One side on the occipital head
Participant milestones
| Measure |
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.
|
No Treatment
The other side of the occipital head of participants did not receive any injection intervention.
|
|---|---|---|
|
Pre-Transcriptomic Analysis
STARTED
|
37 37
|
37 37
|
|
Pre-Transcriptomic Analysis
Split-Person Intervention
|
32 32
|
32 32
|
|
Pre-Transcriptomic Analysis
Migraine Surgery
|
31 31
|
31 31
|
|
Pre-Transcriptomic Analysis
COMPLETED
|
31 31
|
31 31
|
|
Pre-Transcriptomic Analysis
NOT COMPLETED
|
6 6
|
6 6
|
|
Transcriptomic Analysis
STARTED
|
31 31
|
31 31
|
|
Transcriptomic Analysis
COMPLETED
|
18 18
|
18 18
|
|
Transcriptomic Analysis
NOT COMPLETED
|
13 13
|
13 13
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Among 37 total participants enrolled, 31 received the split-person intervention, underwent surgery, and 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). Therefore, a total of 18 participants were included in the analysis.
Baseline characteristics by cohort
| Measure |
Treatment With Onabotulinumtoxin A Injection
n=18 Sides of head
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.
|
No Treatment
n=18 Sides of head
The other side of the occipital head of participants did not receive any injection intervention.
|
Total
n=36 Sides of head
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=18 Participants • Among 37 total participants enrolled, 31 received the split-person intervention, underwent surgery, and 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). Therefore, a total of 18 participants were included in the analysis.
|
0 Participants
n=18 Participants • Among 37 total participants enrolled, 31 received the split-person intervention, underwent surgery, and 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). Therefore, a total of 18 participants were included in the analysis.
|
0 Participants
n=18 Participants • Among 37 total participants enrolled, 31 received the split-person intervention, underwent surgery, and 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). Therefore, a total of 18 participants were included in the analysis.
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=18 Participants • Among 37 total participants enrolled, 31 received the split-person intervention, underwent surgery, and 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). Therefore, a total of 18 participants were included in the analysis.
|
17 Participants
n=18 Participants • Among 37 total participants enrolled, 31 received the split-person intervention, underwent surgery, and 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). Therefore, a total of 18 participants were included in the analysis.
|
34 Participants
n=18 Participants • Among 37 total participants enrolled, 31 received the split-person intervention, underwent surgery, and 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). Therefore, a total of 18 participants were included in the analysis.
|
|
Age, Categorical
>=65 years
|
1 Participants
n=18 Participants • Among 37 total participants enrolled, 31 received the split-person intervention, underwent surgery, and 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). Therefore, a total of 18 participants were included in the analysis.
|
1 Participants
n=18 Participants • Among 37 total participants enrolled, 31 received the split-person intervention, underwent surgery, and 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). Therefore, a total of 18 participants were included in the analysis.
|
2 Participants
n=18 Participants • Among 37 total participants enrolled, 31 received the split-person intervention, underwent surgery, and 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). Therefore, a total of 18 participants were included in the analysis.
|
|
Age, Continuous
|
45 years
STANDARD_DEVIATION 14 • n=18 Participants
|
45 years
STANDARD_DEVIATION 14 • n=18 Participants
|
45 years
STANDARD_DEVIATION 14 • n=18 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=18 Participants
|
17 Participants
n=18 Participants
|
34 Participants
n=18 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=18 Participants
|
1 Participants
n=18 Participants
|
2 Participants
n=18 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
18 Participants
n=18 Participants
|
18 Participants
n=18 Participants
|
18 Participants
n=18 Participants
|
|
Monthly migraine days
|
19 days per month
STANDARD_DEVIATION 10 • n=18 Participants
|
19 days per month
STANDARD_DEVIATION 10 • n=18 Participants
|
19 days per month
STANDARD_DEVIATION 10 • n=18 Participants
|
PRIMARY outcome
Timeframe: One yearPopulation: 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.
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.
Outcome measures
| Measure |
Treatment With OnabotulinumtoxinA Injection
n=18 Sides of head
One side of the occipital head of participants was treated with a total of 40 units of onabotulinumtoxinA injection 30 days prior to their scheduled, study-unrelated, nerve decompression migraine 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.
|
No Treatment
n=18 Sides of head
The other side of the occipital head of participants did not receive any injection intervention.
|
|---|---|---|
|
Inflammatory Gene Expression in Chronic Migraine Patients With OnabotulinumtoxinA Injection Treatment Versus No Treatment
|
44.46156 mRNA units
Interval 12.98994 to 137.8325
|
68.74241 mRNA units
Interval 26.35755 to 191.9613
|
Adverse Events
Botulinum Toxin Type A Injection Arm
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place