(Botox) Mechanisms of Action in Altering the Molecular En... | NCT03381261

NCT03381261

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Beth Israel Deaconess Medical Center	OTHER

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Botulinum toxin type A injection arm	Experimental	All patients will be injected with Botulinum toxin on one side of the back of the head.	Drug: Botulinum toxin type A

Name	Type	Description	Arm Group Labels	Other Names
Botulinum toxin type A	Drug	Injection of Botulinum toxin type A in back of head	Botulinum toxin type A injection arm

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	One year

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
William G. Austen, MD	Massachusetts General Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Massachusetts General Hospital		Boston	Massachusetts	02114	United States

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	No Treatment	The other side of the occipital head of participants did not receive any injection intervention.

Periods

Title

Milestones

Reasons Not Completed

Pre-Transcriptomic Analysis

Type	Comment	Milestone Data
STARTED		FG00037 subjects37 unitsIn this split-person study, a total of 37 participants were enrolled and started the study. For each patient, two sides of the head were each assigned to a different intervention. The unit of measure for the study was "side of head". FG00137 subjects37 unitsIn this split-person study, a total of 37 participants were enrolled and started the study. For each patient, two sides of the head were each assigned to a different intervention. The unit of measure for the study was "side of head".
Split-Person Intervention	The split-person intervention consisted in injecting onabotulinumtoxinA in one side of the occipital head and no injection treatment on the other side.	FG00032 subjects32 unitsAmong the 37 participants who were enrolled, consented and started the study, 32 patients underwent the split-person intervention which consisted in injecting onabotulinumtoxinA in one side of their head and no injection treatment on the other side. FG00132 subjects32 unitsAmong the 37 participants who were enrolled, consented and started the study, 32 patients underwent the split-person intervention which consisted in injecting onabotulinumtoxinA in one side of their head and no injection treatment on the other side.
Migraine Surgery	Participants underwent nerve decompression migraine surgery 30 days following the split-person intervention. During surgery, discarded tissue was collected for transcriptomic analyses.	FG00031 subjects31 unitsAmong the 32 patients who underwent the split-person intervention, 31 underwent nerve decompression migraine surgery within 30 days. Thus, tissue from both sides of the head was collected for 31 patients. FG00131 subjects31 unitsAmong the 32 patients who underwent the split-person intervention, 31 underwent nerve decompression migraine surgery within 30 days. Thus, tissue from both sides of the head was collected for 31 patients.
COMPLETED		FG00031 subjects31 unitsA total of 31 participants completed the study (screened, consented, underwent onabotulinumtoxinA injection on one side of the head and no injection on the other side, underwent nerve decompression surgery, had tissues collected from both sides of occipital head). FG00131 subjects31 unitsA total of 31 participants completed the study (screened, consented, underwent onabotulinumtoxinA injection on one side of the head and no injection on the other side, underwent nerve decompression surgery, had tissues collected from both sides of occipital head).
NOT COMPLETED		FG0006 subjects6 units FG0016 subjects6 units

Transcriptomic Analysis

Type	Comment	Milestone Data
STARTED		FG00031 subjects31 units FG00131 subjects31 units
COMPLETED		FG00018 subjects18 unitsAmong the 31 patients who had tissues collected from both sides of their heads, 18 patients had tissues that were collected which fulfilled all criteria for inclusion for transcriptome analyses and data interpretation following transcriptomic data quality, background thresholding and normalization zesting. The 13 patients who were not included in the analysis are those whose transcriptome data quality failed inclusion criteria.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical	The average age of the patient population was 45 years old (standard deviation 14 years). Patient age range was 21 to 74 years old.

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
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.	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.	Posted		Median	Inter-Quartile Range	mRNA units

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Botulinum Toxin Type A Injection Arm	All patients will be injected with Botulinum toxin on one side of the back of the head. Botulinum toxin type A: Injection of Botulinum toxin type A in back of head

Title	Organization	Phone	Extension	Email
Dr. Lisa Gfrerer	Weill Cornell Medicine	646.962.4250		lig4013@med.cornell.edu

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 7, 2022	Dec 5, 2022	Prot_SAP_000.pdf

Condition Browse Module

ID	Term
D008881	Migraine Disorders
D014277	Trigeminal Neuralgia

ID	Term
D051270	Headache Disorders, Primary
D020773	Headache Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases

Intervention Browse Module

ID	Term
D019274	Botulinum Toxins, Type A

ID	Term
D001905	Botulinum Toxins
D008666	Metalloendopeptidases
D010450	Endopeptidases
D010447	Peptide Hydrolases

FG00118 subjects18 unitsAmong the 31 patients who had tissues collected from both sides of their heads, 18 patients had tissues that were collected which fulfilled all criteria for inclusion for transcriptome analyses and data interpretation following transcriptomic data quality, background thresholding and normalization zesting. The 13 patients who were not included in the analysis are those whose transcriptome data quality failed inclusion criteria.