Functional Effects of Botox on the Brain Using MRS and fMRI

Healthy Clinical Trial

Official title:

Measuring the Functional Effects of Botox on the Brain Using MR Spectroscopy and fMRI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03373162
• Other study ID #: 2017-3377
• Status: Completed
• Phase: Phase 4
• Start date: September 30, 2017
• Est. completion date: March 16, 2018

Study information

• Verified date: May 2020
• Source: University of California, Irvine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 16, 2018
• Est. primary completion date: March 16, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 30 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• 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 .

Locations

Country	Name	City	State
United States	University of California, Irvine	Irvine	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Irvine	Allergan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	15-33 days between pre and post-Botox scans
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.	15-33 days between pre and post-Botox scans
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.	15-33 days between pre and post-Botox scans