BOTOX for Epilepsy

Overseen By Mouhsin Shafi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: Opioids, Muscle relaxants

Disqualifiers: Unstable condition, Psychiatric disorder, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if BOTOX (OnabotulinumtoxinA) can help people with epilepsy by reducing the frequency and severity of their seizures. Researchers are interested in this because epilepsy and migraines often share similar traits and treatments. Suitable candidates have epilepsy that does not respond to medication and experience more than three seizures a month. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and proven effective treatment benefits a broader range of patients.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you must stop all current medications, but you cannot change antiepileptic medication within 2 months before joining. You also cannot use headache prophylactic medication within 28 days before the trial or use muscle relaxants chronically in the 3 months prior to screening.

What is the safety track record for BOTOX?

Research shows that Botox, also known as onabotulinumtoxinA, has been well-studied and is generally considered safe for various uses. In studies, 42.1% of people who received Botox reported side effects, compared to 35.8% of those who received a placebo. Most side effects were mild, such as headaches or irritation in the nose and throat. Another study confirmed Botox's safety even for children with serious conditions, with most side effects being mild.

The FDA has already approved Botox for other conditions, such as migraines and muscle disorders, indicating it is well-tolerated. While using Botox for epilepsy is newer, its safety record in similar conditions supports its potential use in reducing seizures. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard epilepsy treatments that include medications like antiepileptic drugs (AEDs), BOTOX offers a novel approach by using botulinum toxin to potentially reduce seizures. While most treatments for epilepsy work by stabilizing electrical activity in the brain, BOTOX could target muscle-related triggers that may contribute to seizures, offering a unique mechanism of action. Researchers are excited about this treatment because it could provide an alternative for patients who have not responded well to traditional medications, possibly offering a different pathway to manage and control seizures.

What is the effectiveness track record for BOTOX in treating epilepsy?

Research has shown that BOTOX injections might reduce seizure severity. For example, one study found that BOTOX improved seizure frequency and intensity within 24 hours, with some individuals experiencing no seizures within a week. Another study suggested that BOTOX could decrease the likelihood of seizures occurring. While BOTOX has effectively reduced seizure severity, its impact on frequency and duration can vary. These findings suggest BOTOX could help manage seizures, similar to its use for migraines, as the two conditions share some features. Participants in this trial will receive BOTOX therapy to evaluate its effects on seizure frequency and severity. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with pharmaco-resistant focal epilepsy experiencing more than three seizures a month. Participants should not have had recent cranial surgery, changes in epilepsy medication, or botulinum toxin injections recently. Pregnant individuals or those at risk of pregnancy must use contraception.

Inclusion Criteria

I am either male or female.

I have epilepsy with more than 3 seizures a month that doesn't respond to medication.

Exclusion Criteria

You have a mental health condition that might make it hard for you to take part in the trial.

I have not had botulinum A toxin injections in the last 3 months.

I am not eligible for Botox treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-4 weeks

1 visit (in-person)

Baseline Monitoring

Participants undergo 8-week seizure monitoring and baseline 24-hour ambulatory EEG and TMS-EEG-EMG assessments

8 weeks

2 visits (in-person)

Treatment

Participants receive BOTOX injections and continue seizure diary maintenance

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including EEG and TMS assessments

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• BOTOX

Trial Overview The study tests if BOTOX (OnabotulinumtoxinA) injections can reduce the frequency and severity of seizures in people with epilepsy. It's based on similarities between migraine and epilepsy treatments.

How Is the Trial Designed?

Group I: Botox therapy effects on seizure Experimental Treatment 1 Intervention

BOTOX is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Botox for:

• Chronic migraine
• Involuntary muscle contractions or twitching
• Excessive sweating
• Increased saliva
• Overactive bladder
• Crow's Feet
• Glabellar Lines
• Facial Wrinkles
• Orbicularis Oculi
• Platysma Bands

Approved in United States as Botox for:

• Chronic migraine
• Involuntary muscle contractions or twitching
• Excessive sweating
• Increased saliva
• Overactive bladder
• Crow's Feet
• Glabellar Lines
• Facial Wrinkles
• Orbicularis Oculi
• Platysma Bands
• Cervical Dystonia
• Blepharospasm
• Chronic Spasticity
• Bruxism
• Dystonia
• Headache

Approved in Canada as Botox for:

• Similar to those in the United States and European Union, specific details may vary

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

Clobazam is now approved in the USA for treating Lennox-Gastaut syndrome, a type of generalized epilepsy, and is recognized as a safe and well-tolerated adjunctive treatment option based on extensive international experience.

Despite common misconceptions that Lennox-Gastaut syndrome only affects children, this paper emphasizes that it can evolve with age, highlighting the need for neurologists to understand its broader implications and treatment options like clobazam.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clobazam for treatment of epilepsy. Giarratano, M., Standley, K., Benbadis, SR.[2018]

Antiepileptic drugs (AEDs) like carbamazepine (CBZ) and phenytoin (PHT) are recommended as first-line treatments for adults with recurrent partial seizures, based on studies involving U.S. Veterans Administration patients.

Valproate (VPA) is effective for both partial seizures and primary generalized epilepsies, while ethosuximide (ESM) is preferred for typical childhood absence seizures, indicating a tailored approach to epilepsy treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standard approach to antiepileptic drug treatment in the United States. Pellock, JM.[2019]

Serious adverse events following the use of Botulinum Toxin Type A (BoNT-A) in children with spasticity are rare, but careful documentation and informed consent are essential to manage potential litigation risks.

Understanding the differences in perspectives between healthcare providers and the public regarding BoNT-A can help improve the consent process, ensuring patients are well-informed about possible adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum Toxin Type A injections for pediatric spasticity: Keeping our patients informed and practices safe. Wright, E., Fetsko, L.[2021]

Botulinum neurotoxins (BTX), including BOTOX and Myobloc, have received FDA approval for treating conditions like cervical dystonia and cosmetic uses, indicating their expanding therapeutic applications.

Clinical experience has shown a decrease in side effects and secondary resistance to BTX, particularly due to improvements in the formulation of BOTOX that reduce non-toxic proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the botulinum neurotoxins. Carruthers, A., Carruthers, J.[2017]

In a study of 591 children with cerebral palsy who received a total of 2219 botulinum toxin A (BoNT-A) injections, adverse events were reported in 6% of injection episodes during the procedure and 22% at follow-up, indicating that while adverse events are common, they are mostly mild and self-limiting.

Children classified as GMFCS levels IV and V experienced significantly higher rates of systemic adverse events, with incidence rate ratios of 3.92 and 7.37 respectively, suggesting that the severity of cerebral palsy influences the risk of complications following BoNT-A treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severity of cerebral palsy and likelihood of adverse events after botulinum toxin A injections. Swinney, CM., Bau, K., Burton, KLO., et al.[2018]

The FDA has approved several new medications for epilepsy, including rufinamide, lacosamide, and vigabatrin, along with extended-release versions of lamotrigine and levetiracetam, expanding treatment options for patients.

There are important safety considerations with these medications, including potential links to osteoporosis, effects during pregnancy, and increased rates of suicidality, which practitioners need to be aware of when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on anticonvulsant drugs. Chong, DJ., Bazil, CW.[2021]

AbobotulinumtoxinA, approved by the FDA in 2009 for facial aesthetics, is generally well tolerated and has a safety profile similar to other botulinum neurotoxin type A products.

The article discusses various clinical applications and indications for abobotulinumtoxinA, along with important information on handling, storage, and dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of AbobotulinumtoxinA (Dysport). Lorenc, ZP., Kenkel, JM., Fagien, S., et al.[2016]

A study analyzing 162 individual case safety reports of botulinum neurotoxin type A (BoNT-A) in children with cerebral palsy found a significant association between BoNT-A and adverse drug reactions (ADRs), particularly a higher risk of serious outcomes like death (ROR=11.1).

The most common ADRs reported were dysphagia, asthenia, and muscular weakness, indicating that the systemic spread of BoNT-A may contribute to these adverse effects, suggesting that children may experience a higher risk of ADRs compared to adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of botulinum neurotoxin type A in children with cerebral palsy: a pharmaco-epidemiological study in VigiBase. Montastruc, J., Marque, P., Moulis, F., et al.[2017]

Targeted peripheral nerve-directed BOTOX injections significantly improved migraine outcomes in a retrospective study of 223 patients, showing reductions in migraine headache index, headache days per month, and migraine severity over a mean follow-up of 615 days.

While less effective than surgical decompression, this approach offers a promising alternative to traditional BOTOX injections, potentially requiring lower doses and reducing costs for chronic migraine treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Peripheral Nerve-directed Onabotulinumtoxin A Injection for Effective Long-term Therapy for Migraine Headache. Janis, JE., Barker, JC., Palettas, M.[2020]

In a study of 334 children with cerebral palsy receiving botulinum toxin type A (BoNT-A) injections, 23.2% experienced temporary adverse events, but there were no serious complications or deaths, indicating a favorable safety profile.

The study suggests that BoNT-A injections can be administered safely across all levels of the Gross Motor Function Classification System (GMFCS) without the need for restrictions, as the benefits outweigh the temporary adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events and health status following botulinum toxin type A injections in children with cerebral palsy. O'Flaherty, SJ., Janakan, V., Morrow, AM., et al.[2011]

In a study of 13 patients receiving over 360 units of onabotulinumtoxinA within a 3-month period, there were no life-threatening adverse events reported, indicating a favorable safety profile for high-dose administration.

The study found a total of 6 mild adverse events, such as weakness or leg pain, which resolved without complications, suggesting that while some side effects may occur, they are generally manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of adverse events after high doses of onabotulinumtoxinA for multiple indications. Nuanthaisong, U., Abraham, N., Goldman, HB.[2018]

Vigabatrin has been effective in reducing seizure frequency by 50% or more in approximately 50% of children with West syndrome and partial seizures, based on data from over 360 treated children.

The medication has a good safety profile, with mild side effects like drowsiness and agitation, making it a well-tolerated option for children with intractable epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of vigabatrin in the management of infantile epileptic syndromes. Appleton, RE.[2013]

Despite optimal treatment with traditional antiepileptic drugs, 25-40% of epilepsy patients still experience seizures, highlighting the need for new treatment options.

Five new antiepileptic drugs have been approved by the FDA, including gabapentin, lamotrigine, and topiramate for adults with partial seizures, but some, like felbamate and lamotrigine, may have significant side effects and require careful management by experienced physicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newer antiepileptic drugs: gabapentin, lamotrigine, felbamate, topiramate and fosphenytoin. Curry, WJ., Kulling, DL.[2018]

Botulinum Toxin (BoNT) is an effective treatment for hypertonia in children, but while serious adverse events are rare, they can have significant consequences for patient health.

Physicians must carefully weigh the risks and benefits of BoNT treatment, considering factors like medical comorbidities and dosing techniques to enhance safety and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pragmatic approach to Botulinum Toxin safety. Vova, JA., Leung, E.[2021]

In a clinical trial involving 144 children with spastic cerebral palsy, letibotulinum toxin A (Botulax) was found to be as effective as onabotulinum toxin A (Botox) in treating dynamic equinus foot deformity, with similar safety profiles.

The responder rates for both treatments were comparable at 12 weeks post-injection, indicating that letibotulinum toxin A can be a viable alternative to onabotulinum toxin A for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Letibotulinum Toxin A for the Treatment of Dynamic Equinus Foot Deformity in Children with Cerebral Palsy: A Randomized Controlled Trial. Chang, HJ., Hong, BY., Lee, SJ., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3371349/

Botulinum Toxin Injections for Simple Partial Motor Seizures ... Seizure severity was reduced, but seizure frequency and duration were unaffected. For these patients, BTX was effective in temporarily relieving ...

2. withpower.com withpower.com/trial/phase-4-seizures-11-2023-cb0ac

BOTOX for Epilepsy · Info for Participants For example, one study found that BOTOX was as effective and safe as another similar treatment for improving foot deformity in children with cerebral palsy.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6726074/

Antiepileptic Effects of Botulinum Neurotoxin E - PMC PHT induced an average twofold delay in the onset of EEG seizures and a 2.5-fold reduction in the time spent in seizure activity (Student's t test; p < 0.01).

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0920121117302024

Refractory focal motor seizures controlled with ... Improvement in seizure frequency and intensity was noted within 24 h of BoT injection and complete resolution in one week. BoT was continued at 4–8 monthly ...

5. trial.medpath.com trial.medpath.com/clinical-trial/82be441bb66d0dc5/botox-effects-seizure-severity

BOTOX Effects on Seizure Severity and Susceptibility - MedPath 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10682279/

Safety and tolerability of onabotulinumtoxinA in ... AEs were reported in 42.1% and 35.8% of the onabotulinumtoxinA and placebo groups, respectively, and most commonly (≥2%) were headache, nasopharyngitis, ...

7. fda.gov fda.gov/media/169198/download

Botox Postmarketing Safety Review This review evaluates FDA Adverse Event Reporting System (FAERS) reports for Botox. (onabotulinumtoxinA) in pediatric patients <18 years of age.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3705276/

Safety of Botulinum Toxin A in Children and Adolescents ... In conclusion, treatment with BoNT-A was safe; adverse reactions were mostly mild even for severely affected patients. Their appearance did not ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01600716

Safety and Efficacy Study of OnabotulinumtoxinA for the ... This study will evaluate the safety and efficacy of OnabotulinumtoxinA (BOTOX®) for the treatment of urinary incontinence due to NDO in non-catheterizing ...