MigrainePhase 4NCT03381261

(Botox) Mechanisms of Action in Altering the Molecular Environment in Which Pain Fibers Exist

A Phase 4 study testing Botulinum toxin type A in people with Migraine, run by Massachusetts General Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Migraine
What is being tested?: Botulinum toxin type A
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 1 siteUnited States
Study dates: 1 Dec 2017to 1 Dec 2023
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Massachusetts General Hospital
Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: Novel Concepts for OnabotulinumtoxinA (Botox) Mechanisms of Action: Role in Altering the Molecular Environment in Which Pain Fibers Exist

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.

Read the 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.

Conditions: Migraine
Being tested: Botulinum toxin type A
Keywords: chronic migraine, trigeminal neuralgia, migraine surgery, nerve decompression
Medical subject headings: Migraine Disorders, Trigeminal Neuralgia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Botulinum toxin type ADrug
Also called Botox
Injection of Botulinum toxin type A in back of head

Study groups in NCT03381261
Study group	Role	What they receive
Botulinum toxin type A injection arm	Experimental	All patients will be injected with Botulinum toxin on one side of the back of the head. Receives: Drug: Botulinum toxin type A

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: One year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Dec 20171 Dec 2023

First posted21 Dec 2017
Study start1 Dec 2017
Primary completion1 Aug 2023
Study completion1 Dec 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for MigraineStudies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03381261
Sponsor's protocol ID: 2017P001813
Status last verified: Mar 2025
First submitted: 18 Dec 2017
Last updated: 24 Mar 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Study of the Glymphatic System in Migraine
Migraine
Active, not recruiting
Clinical and Neurophysiological Effects of tDCS to Visual and Motor Cortex in Migraine
Migraine
Active, not recruiting
App-Based Migraine Treatment: The Health enSuite Study
Migraine, Migraine With Aura
Not yet recruiting
A Prospective Study of Rimegepant for Short-term Preventive Treatment of Night-shift-related Migraine in Healthcare Professionals
Migraine Disorders
Recruiting
Marine Lipids Ease Painful TMD
Temporomandibular Disorder (TMD)

All Migraine trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Novel Concepts for OnabotulinumtoxinA (Botox) Mechanisms of Action: Role in Altering the Molecular Environment in Which Pain Fibers Exist
ClinicalTrials.gov ID: NCT03381261
Acronym / sponsor ID: 2017P001813
Conditions: Migraine
Keywords: chronic migraine, trigeminal neuralgia, migraine surgery, nerve decompression
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Collaborators: Beth Israel Deaconess Medical Center
Study start: 1 Dec 2017 (actual)
Primary completion: 1 Aug 2023 (actual)
Study completion: 1 Dec 2023 (actual)
First posted: 21 Dec 2017 (actual)
Results: Posted 24 Mar 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Botulinum toxin type A injection arm	Experimental	Drug: Botulinum toxin type AAll patients will be injected with Botulinum toxin on one side of the back of the head.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (3 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Botulinum toxin type AAlso: BotoxInjection of Botulinum toxin type A in back of head	Drug	Botulinum toxin type A injection arm

Primary outcome

Inflammatory Gene Expression in Chronic Migraine Patients With OnabotulinumtoxinA Injection Treatment Versus No Treatment
Time frame: 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.

Results and safety

Results posted to the registry on 24 Mar 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment With Onabotulinumtoxin A Injection	37	31
No Treatment	37	31

Primary outcome: Inflammatory Gene Expression in Chronic Migraine Patients With OnabotulinumtoxinA Injection Treatment Versus No Treatment

Time frame: One year. Median (Inter-Quartile Range). Unit: mRNA units

Measure	Treatment With OnabotulinumtoxinA Injection n = 18	No Treatment n = 18
Value	44.46156 (12.98994 to 137.8325)	68.74241 (26.35755 to 191.9613)

Treatment With OnabotulinumtoxinA Injection vs No Treatment: p <0.0001, t-test, 2 sided

Population analysed: 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.

Adverse events

Time frame: For each patient, from the time of informed consent to 6 years following surgery, self-reported adverse events were reviewed by the study physician during patient contact and follow-ups.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Botulinum Toxin Type A Injection Arm	0 of 37 (0%)	0 of 37 (0%)	0 of 37

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Migraine

RecruitingObservational study
Study of the Glymphatic System in Migraine
Migraine
Active, not recruiting
Clinical and Neurophysiological Effects of tDCS to Visual and Motor Cortex in Migraine
Migraine
Active, not recruiting
App-Based Migraine Treatment: The Health enSuite Study
Migraine, Migraine With Aura
Not yet recruiting
A Prospective Study of Rimegepant for Short-term Preventive Treatment of Night-shift-related Migraine in Healthcare Professionals
Migraine Disorders
Recruiting
Marine Lipids Ease Painful TMD
Temporomandibular Disorder (TMD)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

William G. Austen, MD principal investigator

Massachusetts General Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Botulinum toxin type A in people with Migraine, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Inflammatory Gene Expression in Chronic Migraine Patients With OnabotulinumtoxinA Injection Treatment Versus No Treatment (time frame: One year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03381261.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2025.