HealthyPhase 4NCT03373162
Functional Effects of Botox on the Brain Using MRS and fMRI
A Phase 4 study testing onabotulinumtoxinA in people with Healthy, run by University of California, Irvine at 1 site in United States.
Trial summary
The injection of BOTOX into peripheral muscles has been shown to have therapeutic effects in a growing number of indications including disorders involving skeletal muscle (e.g., strabismus, blepharospasm, cervical dystonia, spasticity, cosmetic), smooth muscle (e.g., bladder), glands (axillary hyperhidrosis) and… Read more about this study
- Who is it for?
- Ages 30 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- onabotulinumtoxinA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2017to 16 Mar 2018
- 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 30 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Females
- Ages 30-40 years of age
- Right-handed
- Normal or corrected-to-normal vision
- No history of psychiatric, neurological, or medical co-morbidities that might interfere with normal brain functioning
- Fluent in English
- Moderate to severe glabellar lines
Who cannot join
- Pregnancy
- Ferrous metal, a pacemaker, or other battery-operated device implanted in the body
- Claustrophobia
- Known hypersensitivity to Botulinum Toxin
- Infection on the forehead or between the eyes
- Urinary tract infection
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Irvine
Irvine, California, 92697
About this study
Official title: Measuring the Functional Effects of Botox on the Brain Using MR Spectroscopy and fMRI
The injection of BOTOX into peripheral muscles has been shown to have therapeutic effects in a growing number of indications including disorders involving skeletal muscle (e.g., strabismus, blepharospasm, cervical dystonia, spasticity, cosmetic), smooth muscle (e.g., bladder), glands (axillary hyperhidrosis) and nociceptive pain (e.g. migraine) (Brin. 2014). Recently, several studies have suggested that peripheral BOTOX injections in the region of the glabellar lines (muscles around the eyes) may be effective in treating major depression and chronic migraine. However, the mechanism underlying the effect of peripheral BOTOX injections on the brain is not well understood. Therefore, the Investigators propose to further explore the functional effects of BOTOX injections on brain in healthy controls. The approach will involve the measurement of brain metabolites in the brainstem using MRS as well as an investigation of the functioning and connectivity between regions of the brain using resting state MRI and high resolution fMRI.
Read the detailed description
Participants will receive one MRI scan session prior to a standardized, clinical dose of BOTOX injected into the forehead per FDA-approved procedures. Participants will then undergo a second MRI scan session 2-3 weeks later, after the BOTOX has taken maximal effect. Examining fMRI of the brainstem and the functional connectivity of the brainstem and connections to cortex, may provide additional insight into the effects of BOTOX on neurologic and psychiatric disorders.
- Conditions
- Healthy
- Being tested
- onabotulinumtoxinA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
onabotulinumtoxinADrug
Also called Botox
This study is a pre- and post-design. One scan will be collected prior to BOTOX injection and the second will be collected 14-21 days post-injection. BOTOX injections will be limited to 20 units in the glabellar area, as approved by the FDA .
| Study group | Role | What they receive |
|---|---|---|
| MRI Scans Pre and Post-Botox Injection | Experimental | Participants will receive MRI scans pre and post-Botox injection, including magnetic resonance spectroscopy, structural, and functional MRI. Receives: Drug: onabotulinumtoxinA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glutamate + Glutamine (Glx)/Creatine Ratio as Measured by MRS in the Brainstem Pre and Post-Botox
Determine whether there are metabolic differences in the brain stem in healthy individuals as a result of BOTOX using MRS. Participants were scanned 1-13 days prior to Botox injections in the glabellar region and then again 14-21 days post-injection when the Botox had reached effectiveness. Metabolite FIDs were averaged within each task and processed using TARQUIN (v.4.3.6) software for spectral fitting. The acquired MRS spectra was corrected for tissue type and T2 relaxation differences. Using TARQUIN we obtained values for Glutamate + Glutamine (Glx), normalized by Creatine.
Measured: 15-33 days between pre and post-Botox scans
Change From Baseline in Functional MRI Mean Blood Oxygen Level Dependent (BOLD) Response in the Amygdala
Understand the effect of BOTOX on functional activity (measured using fMRI) in the brain. Participants were scanned 1-13 days prior to Botox injections in the glabellar region and then again 14-21 days post-injection when the Botox had reached effectiveness. Participants viewed Happy and Angry faces and rated each one as pleasant or unpleasant. We then masked activity in the amygdala to investigate the difference in BOLD response for collapsed across emotion following Botox injections.
Measured: 15-33 days between pre and post-Botox scans
Secondary outcomes (1)
Number of Participants With Structural Brain Volume Change Following Botox Injections
Participants were scanned 1-13 days prior to Botox injections in the glabellar region and then again 14-21 days post-injection when the Botox had reached effectiveness. Structural scans for each participant were segmented using Freesurfer's automatic software for volumetric measures and then normalized by dividing by total intracranial volume for each participant. We then conducted t-tests for pre- vs. post- BOTOX injections to investigate any structural changes.
Measured: 15-33 days between pre and post-Botox scans
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2017
- Study start30 Sep 2017
- Primary completion16 Mar 2018
- Study completion16 Mar 2018
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- 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
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Irvine
- Sponsor type
- University, hospital or other
- Collaborators
- Allergan
- Responsible party
- Sponsor
- Investigators
- Craig Stark, PhD, Principal investigator, University of California, Irvine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03373162
- Sponsor's protocol ID
- 2017-3377
- Status last verified
- May 2020
- First submitted
- 2 Oct 2017
- Last updated
- 1 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stark S, Stark C, Wong B, Brin MF. Modulation of amygdala activity for emotional faces due to botulinum toxin type A injections that prevent frowning. Sci Rep. 2023 Feb 27;13(1):3333. doi: 10.1038/s41598-023-29280-x.
PubMed 36849797
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measuring the Functional Effects of Botox on the Brain Using MR Spectroscopy and fMRI
- ClinicalTrials.gov ID
- NCT03373162
- Acronym / sponsor ID
- 2017-3377
- Conditions
- Healthy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of California, IrvineUniversity, hospital or other
- Collaborators
- Allergan
- Study start
- 30 Sep 2017 (actual)
- Primary completion
- 16 Mar 2018 (actual)
- Study completion
- 16 Mar 2018 (actual)
- First posted
- 14 Dec 2017 (actual)
- Results
- Posted 26 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The injection of BOTOX into peripheral muscles has been shown to have therapeutic effects in a growing number of indications including disorders involving skeletal muscle (e.g., strabismus, blepharospasm, cervical dystonia, spasticity, cosmetic), smooth muscle (e.g., bladder), glands (axillary hyperhidrosis) and nociceptive pain (e.g. migraine) (Brin. 2014). Recently, several studies have suggested that peripheral BOTOX injections in the region of the glabellar lines (muscles around the eyes) may be effective in treating major depression and chronic migraine. However, the mechanism underlying the effect of peripheral BOTOX injections on the brain is not well understood. Therefore, the Investigators propose to further explore the functional effects of BOTOX injections on brain in healthy controls. The approach will involve the measurement of brain metabolites in the brainstem using MRS as well as an investigation of the functioning and connectivity between regions of the brain using resting state MRI and high resolution fMRI.
Detailed description
Participants will receive one MRI scan session prior to a standardized, clinical dose of BOTOX injected into the forehead per FDA-approved procedures. Participants will then undergo a second MRI scan session 2-3 weeks later, after the BOTOX has taken maximal effect. Examining fMRI of the brainstem and the functional connectivity of the brainstem and connections to cortex, may provide additional insight into the effects of BOTOX on neurologic and psychiatric disorders.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MRI Scans Pre and Post-Botox Injection | Experimental | Drug: onabotulinumtoxinAParticipants will receive MRI scans pre and post-Botox injection, including magnetic resonance spectroscopy, structural, and functional MRI. |
Who may qualify
- Ages
- 30 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Females
- Ages 30-40 years of age
- Right-handed
- Normal or corrected-to-normal vision
- No history of psychiatric, neurological, or medical co-morbidities that might interfere with normal brain functioning
Key exclusion criteria (6 listed)
- Pregnancy
- Ferrous metal, a pacemaker, or other battery-operated device implanted in the body
- Claustrophobia
- Known hypersensitivity to Botulinum Toxin
- Infection on the forehead or between the eyes
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 |
|---|---|---|
| onabotulinumtoxinAAlso: BotoxThis study is a pre- and post-design. One scan will be collected prior to BOTOX injection and the second will be collected 14-21 days post-injection. BOTOX injections will be limited to 20 units in the glabellar area, as approved by the FDA . | Drug | MRI Scans Pre and Post-Botox Injection |
Primary outcome
Glutamate + Glutamine (Glx)/Creatine Ratio as Measured by MRS in the Brainstem Pre and Post-Botox
Time frame: 15-33 days between pre and post-Botox scans
Determine whether there are metabolic differences in the brain stem in healthy individuals as a result of BOTOX using MRS. Participants were scanned 1-13 days prior to Botox injections in the glabellar region and then again 14-21 days post-injection when the Botox had reached effectiveness. Metabolite FIDs were averaged within each task and processed using TARQUIN (v.4.3.6) software for spectral fitting. The acquired MRS spectra was corrected for tissue type and T2 relaxation differences. Using TARQUIN we obtained values for Glutamate + Glutamine (Glx), normalized by Creatine.
Change From Baseline in Functional MRI Mean Blood Oxygen Level Dependent (BOLD) Response in the Amygdala
Time frame: 15-33 days between pre and post-Botox scans
Understand the effect of BOTOX on functional activity (measured using fMRI) in the brain. Participants were scanned 1-13 days prior to Botox injections in the glabellar region and then again 14-21 days post-injection when the Botox had reached effectiveness. Participants viewed Happy and Angry faces and rated each one as pleasant or unpleasant. We then masked activity in the amygdala to investigate the difference in BOLD response for collapsed across emotion following Botox injections.
1 secondary outcome
Number of Participants With Structural Brain Volume Change Following Botox Injections
Time frame: 15-33 days between pre and post-Botox scans
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36849797Stark S, Stark C, Wong B, Brin MF. Modulation of amygdala activity for emotional faces due to botulinum toxin type A injections that prevent frowning. Sci Rep. 2023 Feb 27;13(1):3333. doi: 10.1038/s41598-023-29280-x.
- Individual participant dataSharing planned: No
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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.
Craig Stark, PhD principal investigator
University of California, Irvine
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 onabotulinumtoxinA in people with Healthy, run by University of California, Irvine 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 7 inclusion and 6 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 1 Jun 2020. 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 26 Apr 2019). 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?
Glutamate + Glutamine (Glx)/Creatine Ratio as Measured by MRS in the Brainstem Pre and Post-Botox (time frame: 15-33 days between pre and post-Botox scans). The study lists 2 primary outcomes in all. 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 NCT03373162, which also lists 1 linked publication.
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 1 Jun 2020.