Healthy
Conditions
Brief 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 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.
Interventions
DRUGonabotulinumtoxinA
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 .
Sponsors
Allergan
University of California, Irvine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glutamate + Glutamine (Glx)/Creatine Ratio as Measured by MRS in the Brainstem Pre and Post-Botox | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Structural Brain Volume Change Following Botox Injections | 15-33 days between pre and post-Botox scans | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pre-Post Participants will receive MRI scans pre and post-Botox injection
onabotulinumtoxinA: 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 . | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Pre-Post |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| BOLD fMRI activity in Left Amygdala: Angry faces vs baselines task | .08 Beta values STANDARD_DEVIATION 0.08 |
| BOLD fMRI activity in Left Amygdala: Happy faces vs baselines task | 1.4 Beta value STANDARD_DEVIATION 0.06 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| MRS measures of Glx normalized to Creatine | 1.9 Concentration Ratio STANDARD_DEVIATION 0.49 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
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.
Time frame: 15-33 days between pre and post-Botox scans
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MRI Scans Pre and Post-Botox Injection | Change From Baseline in Functional MRI Mean Blood Oxygen Level Dependent (BOLD) Response in the Amygdala | -1.7 fMRI BOLD in Left Amygdala | Standard Error 0.45 |
Primary
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.
Time frame: 15-33 days between pre and post-Botox scans
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MRI Scans Pre and Post-Botox Injection | Glutamate + Glutamine (Glx)/Creatine Ratio as Measured by MRS in the Brainstem Pre and Post-Botox | .12 Brainstem GLX/Cr | Standard Error 0.44 |
Secondary
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.
Time frame: 15-33 days between pre and post-Botox scans
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MRI Scans Pre and Post-Botox Injection | Number of Participants With Structural Brain Volume Change Following Botox Injections | 0 Participants |