Functional Effects of Botox on the Brain Using MRS and fMRI

NCT03373162 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2017-3377
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Number of Participants With Structural Brain Volume Change Following Botox Injections

  15-33 days between pre and post-Botox scans

Study Arms (1)

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.

Drug: onabotulinumtoxinA

Interventions

onabotulinumtoxinA DRUG

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 .

Also known as: Botox

MRI Scans Pre and Post-Botox Injection

Eligibility Criteria

• Age: 30 Years - 40 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Irvine: lead
• Allergan: collaborator

Study Sites (1)

University of California, Irvine

Irvine, California, 92697, United States

Location

Related Publications (1)

• 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.

  PMID: 36849797 DERIVED

MeSH Terms

Interventions

Botulinum Toxins, Type A

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Dr. Craig Stark, Professor
• Organization: University of California, Irvine

cestark@uci.edu

949-824-4201

Study Officials

• Craig Stark, PhD

  University of California, Irvine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2017
• First Posted: December 14, 2017
• Study Start: September 30, 2017
• Primary Completion: March 16, 2018
• Study Completion: March 16, 2018
• Last Updated: June 1, 2020
• Results First Posted: April 26, 2019

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)