Functional Effects of Botox on the Brain Using MRS and fMRI

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: onabotulinumtoxinA

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MRI Scans Pre and Post-Botox Injection; Participants will receive MRI scans pre and post-Botox injection, including magnetic resonance spectroscopy, structural, and functional MRI.	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 .; Other Names: Botox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: Allergan
• Investigators: Principal Investigator: Craig Stark, PhD, University of California, Irvine

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2017
• Primary Completion (Actual): March 16, 2018
• Study Completion (Actual): March 16, 2018

Study Registration Dates

• First Submitted: October 2, 2017
• First Submitted That Met QC Criteria: December 12, 2017
• First Posted (Actual): December 14, 2017

Study Record Updates

• Last Update Posted (Actual): June 1, 2020
• Last Update Submitted That Met QC Criteria: May 15, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 2017-3377

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No