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: Unknown

3 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 data supports the idea that BOTOX for Epilepsy is an effective drug?

The available research does not provide specific data supporting the effectiveness of BOTOX for treating epilepsy. Instead, it discusses the use of BOTOX for other conditions like cerebral palsy and migraine headaches. 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. Another study mentioned BOTOX as an FDA-approved treatment for chronic migraine headaches. However, there is no direct evidence in the provided information about its effectiveness for epilepsy. ^{1 2 3 4 5}

What safety data is available for BOTOX used in epilepsy treatment?

Safety data for BOTOX, also known as onabotulinumtoxinA, includes studies on its use in various conditions. Adverse events are generally infrequent but can occur, especially at high doses or in patients with comorbidities. Studies in children with cerebral palsy and pediatric spasticity show that while serious adverse events are rare, they can lead to significant morbidity. Proper documentation and informed consent are crucial to minimize risks. Overall, BOTOX is considered well-tolerated, with adverse events similar to other botulinum toxin products. ^{6 7 8 9 10}

Is the drug BOTOX a promising treatment for epilepsy?

The provided research articles do not mention BOTOX as a treatment for epilepsy, so there is no information to suggest that BOTOX is a promising treatment for epilepsy. ^{11 12 13 14 15}

Eligibility Criteria

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 am between 18 and 85 years old.

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.

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Switzerland 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. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Targeted Peripheral Nerve-directed Onabotulinumtoxin A Injection for Effective Long-term Therapy for Migraine Headache. [2020]

3. Canada pubmed.ncbi.nlm.nih.gov

Update on the botulinum neurotoxins. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Adverse events and health status following botulinum toxin type A injections in children with cerebral palsy. [2011]

5. England pubmed.ncbi.nlm.nih.gov

Severity of cerebral palsy and likelihood of adverse events after botulinum toxin A injections. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

A review of AbobotulinumtoxinA (Dysport). [2016]

8. United States pubmed.ncbi.nlm.nih.gov

Incidence of adverse events after high doses of onabotulinumtoxinA for multiple indications. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

A pragmatic approach to Botulinum Toxin safety. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of botulinum neurotoxin type A in children with cerebral palsy: a pharmaco-epidemiological study in VigiBase. [2017]

11. United States pubmed.ncbi.nlm.nih.gov

Update on anticonvulsant drugs. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Clobazam for treatment of epilepsy. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

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

14. United States pubmed.ncbi.nlm.nih.gov

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

15. United States pubmed.ncbi.nlm.nih.gov

Newer antiepileptic drugs: gabapentin, lamotrigine, felbamate, topiramate and fosphenytoin. [2018]