BOTOX Effects on Seizure Severity and Susceptibility
Trial Snapshot
- Phase
- Phase 4
- Status
- Terminated
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- • Reduction in incidence of generalized seizures
Study Overview
Brief Summary
The purpose of this research is to determine whether BOTOX injections will reduce seizure frequency and severity. We chose to test its effects on epilepsy because epilepsy and migraine have common features so, are often treated with common drugs.
Detailed Description
Goals:
The purpose of this study is to determine whether BOTOX injections into the scalp raise seizure threshold such that focal seizures are less likely to occur, and less likely to generalize.
Objectives:
- To test whether scalp BOTOX injections mitigate seizure frequency or seizure severity. This objective will be tested using a prospective clinical observation in patients with focal epilepsy (see definitions below)
- To test whether quantitative measures of seizures susceptibility (cortical excitability) are altered by scalp BOTOX injections. This objective will be tested using 24-hour ambulatory scalp EEG recording and transcranial magnetic stimulation (TMS) with simultaneous EEG/EMG a noninvasive tool to measure cortical excitability (Tsuboyama et al 2019).
Clarification of terminology:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with focal drug-resistant epilepsy (see inclusion and
Exclusion Criteria
- •Potential study subjects will be provided an informed consent form (ICF) to review. Those who are interested in participating will provide informed consent and then be screened for eligibility (inclusion/exclusion criteria). Individuals screened as potential study subjects must meet all the following inclusion criteria and none of the following exclusion criteria.
- •Inclusion criteria:
- •Age: 18-85 years, inclusive
- •Sex: Males and females
- •Pharmaco-resistant focal epilepsy with >3 seizures a month
- •Exclusion criteria:
- •Cranial or scalp surgery within 3 months of recruitment
- •Change in antiepileptic medication <2 months before recruitment
- •History of status epilepticus within 12 months of recruitment
- •History of psychogenic nonepileptic seizures
- •History of poor medication compliance
- •Any unstable medical condition
- •Any psychiatric disorder that could interfere with trial participation
- •Substance use disorders within the past six months
- •Pregnancy, breastfeeding, or planning a pregnancy during the trial; unable or unwilling to use a reliable form of contraception during the trial - All individuals of childbearing potential will undergo urine pregnancy testing
- •TMS exclusion only (If a participant does not meet TMS criteria, they will not be excluded from the study/the TMS assessments will not be completed):
- •Intracranial metal implants (excluding dental fillings) or devices such as pacemaker, medication pump, nerve stimulator, TENS unit, ventriculo-peritoneal shunt unless cleared by the responsible covering TMS MD.
- •Any intracranial lesions or prior brain surgeries other than minor procedures as reviewed and approved by the TMS MD (e.g. history of brain biopsy, depth electrodes, ICP monitoring, intraventricular and subdural drains…)
- •Exclusion criteria for Botox
- •History of botulinum A toxin injection within 3 months of recruitment
- •Allergy to botulinum toxin
- •Any medical condition that might put participants at increased risk if exposed to onabotulinumtoxinA (e.g. neuromuscular diseases such as myasthenia gravis, Eaton-Lambert Syndrome, amyotrophic lateral sclerosis)
- •Use of any headache prophylactic medication within 28 days before start of baseline
- •History of "complicated" migraine
- •Fibromyalgia
- •Use of opioids as acute pain medication
- •Skin problems, infections, profound atrophy, or excessive weakness in the target areas of the injection sites
- •Concurrent chronic use or chronic use in the 3 months prior to the screening period of muscle relaxants
Arms & Interventions
Botox therapy effects on seizure
Intervention: OnabotulinumtoxinA 145 UNT [Botox] (Drug)
Outcomes
Primary Outcomes
• Reduction in incidence of generalized seizures
Time Frame: 150 days
Frequency of generalized seizure will be averaged per time blocks as follows: (1) baseline, 8 weeks before botulinum A toxin injection, (2) 0-4 weeks after BOTOX injections, and (3) 5-12 weeks after BOTOX injection
• Reduction in incidence of focal seizures with impaired awareness
Time Frame: 150 days
Frequency of focal seizures with impaired awareness will be averaged per time blocks as follows: (1) baseline, 8 weeks before botulinum A toxin injection, (2) 0-4 weeks after BOTOX injections, and (3) 5-12 weeks after BOTOX injection
Change in Net Cortical Excitability Metrics
Time Frame: 150 days
TMS metrics of rMT, CSP, LICI, and TMS-EEG excitability metrics will each be averaged over at least 20 trials per subject per time block (at baseline, and 3 weeks and 8 weeks after BOTOX injections). Per metric mean values will then be compared by one-way repeated measures ANOVA.
Secondary Outcomes
- • Reduction in net cortical excitability metrics(150 days)
- • Improvement in quality-of-life metrics(150 days)
- • Reduction in overall seizure frequency(150days)
- Change in Quality-of-life Metrics(150 days)
Investigators
Rami Burstein
John Hedley-Whyte Professor of Anaesthesia
Beth Israel Deaconess Medical Center