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Functional Effects of Botox on the Brain Using MRS and fMRI

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ClinicalTrials.gov Identifier: NCT03373162
Recruitment Status : Completed
First Posted : December 14, 2017
Results First Posted : April 26, 2019
Last Update Posted : April 26, 2019
Sponsor:
Collaborator:
Allergan
Information provided by (Responsible Party):
University of California, Irvine

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: onabotulinumtoxinA Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Measuring the Functional Effects of Botox on the Brain Using MR Spectroscopy and fMRI
Actual Study Start Date : September 30, 2017
Actual Primary Completion Date : November 1, 2017
Actual Study Completion Date : November 1, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Botox

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 Name: Botox




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Number of Participants With Structural Brain Volume Change Following Botox Injections [ Time Frame: 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.



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Ages Eligible for Study:   30 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03373162


Locations
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United States, California
University of California, Irvine
Irvine, California, United States, 92697
Sponsors and Collaborators
University of California, Irvine
Allergan
Investigators
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Principal Investigator: Craig Stark, PhD University of California, Irvine
  Study Documents (Full-Text)

Documents provided by University of California, Irvine:
Study Protocol  [PDF] January 10, 2017
Statistical Analysis Plan  [PDF] January 7, 2017


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Responsible Party: University of California, Irvine
ClinicalTrials.gov Identifier: NCT03373162     History of Changes
Other Study ID Numbers: 2017-3377
First Posted: December 14, 2017    Key Record Dates
Results First Posted: April 26, 2019
Last Update Posted: April 26, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Botulinum Toxins, Type A
abobotulinumtoxinA
Neuromuscular Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents