Ibuprofen + Nifedipine for Post-Seizure Symptoms in Epilepsy

Recruiting at 1 trial location

Overseen By Paolo Federico, MD, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Calgary

Must not be taking: COX-2 inhibitors, Calcium channel blockers

Disqualifiers: Multiple seizure zones, Imaging contraindications, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5-40 days

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how ibuprofen or nifedipine might alleviate post-seizure symptoms, such as poor blood flow and cognitive issues. Participants will be divided into three groups: one will receive ibuprofen, another nifedipine (a medication for high blood pressure), and the last group will receive a placebo (a pill with no active medicine). It suits individuals over 16 who experience seizures more than once a week and can complete cognitive tests. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have taken a COX-2 inhibitor or calcium channel blocker in the last 2 months.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In previous studies, ibuprofen has sometimes caused side effects like dizziness and trouble walking. It can also increase the levels of certain seizure medications, potentially leading to more side effects. For some individuals, it may cause psychiatric and behavioral symptoms more frequently than other similar drugs.

Nifedipine helps by relaxing blood vessels to lower blood pressure, but this might result in side effects such as very low blood pressure, chest pain, or even heart problems in some cases.

Both ibuprofen and nifedipine are generally well-tolerated for their usual uses, but limited safety information exists for treating post-seizure symptoms in epilepsy. As this is a phase 2 trial, researchers are still studying the safety of these drugs in this context. However, their use in other conditions provides a basic idea of their possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using ibuprofen and nifedipine for post-seizure symptoms in epilepsy because they might offer a fresh approach compared to standard antiepileptic drugs. Most epilepsy treatments focus on preventing seizures, but these medications aim to ease symptoms after a seizure happens. Ibuprofen, an anti-inflammatory, could potentially reduce swelling and pain post-seizure, while nifedipine, a calcium channel blocker, might help stabilize blood flow in the brain. This combination could lead to faster recovery times and better overall management of post-seizure symptoms.

What evidence suggests that this trial's treatments could be effective for post-seizure symptoms in epilepsy?

Research suggests that ibuprofen, which participants in this trial may receive, might help with seizures by reducing inflammation. Animal studies have shown that it can lessen the number, intensity, and length of seizures. Importantly, it does not increase the risk of seizures. Meanwhile, nifedipine, another treatment option in this trial, affects calcium in the body, and research indicates it can make seizures less severe. Some studies found that people taking nifedipine experienced fewer partial seizures. Both treatments show potential in managing symptoms related to epilepsy. ^{6 7 8 9 10}

Who Is on the Research Team?

Paolo Federico, MD, PhD

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for individuals over 16 years old with epilepsy who have more than one seizure per week and can complete cognitive tests. It's not suitable for those with multiple seizure zones, allergies to ibuprofen or nifedipine, recent use of certain inhibitors or blockers, or contraindications to brain imaging.

Inclusion Criteria

I experience more than one seizure per week.

I am older than 16 years.

I can complete tests that measure my thinking skills.

Exclusion Criteria

I am allergic or cannot take ibuprofen or nifedipine.

I have taken COX-2 inhibitors or calcium channel blockers in the last 2 months.

You cannot have CT or MR imaging due to specific health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either placebo, ibuprofen, or nifedipine for at least five days prior to the first blood flow study and continue until the baseline study is obtained after the postictal study has been completed

5-40 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ibuprofen
• Nifedipine
• Placebo

Trial Overview The study examines the effects of ibuprofen and nifedipine on blood flow and neurological function after seizures in epilepsy patients. Participants will be randomly assigned to receive either ibuprofen, nifedipine, or a placebo.

How Is the Trial Designed?

Group I: Nifedipine Experimental Treatment 1 Intervention

Patients will receive nifedipine 10 mg po tid for 2 days, then 20 mg po tid, thereafter for at least five days prior to the first blood flow study. They will continue to receive nifedipine until the baseline study is obtained after the postictal study has been completed.

Group II: Ibuprofen Experimental Treatment 1 Intervention

Patients will receive ibuprofen 400 mg by mouth three times a day (po tid) for at least five days prior to the first blood flow study. They will continue to receive ibuprofen until the baseline study is obtained after the postictal study has been completed.

Group III: Placebo Placebo Group 1 Intervention

Patients will receive placebo for at least five days prior to the first blood flow study. They will continue to receive placebo until the baseline study is obtained after the postictal study has been completed.

Ibuprofen is already approved in United States, Canada, European Union, Japan, China, Switzerland for the following indications:

Approved in United States as Advil for:

• Pain relief
• Fever reduction
• Inflammation

Approved in Canada as Motrin for:

• Pain relief
• Fever reduction
• Inflammation

Approved in European Union as Nurofen for:

• Pain relief
• Fever reduction
• Inflammation

Approved in Japan as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation

Approved in China as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation

Approved in Switzerland as Ibuprofen for:

• Pain relief
• Fever reduction
• Inflammation

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Published Research Related to This Trial

In a rat model of chronic epilepsy induced by pentylenetetrazol, ibuprofen significantly reduced seizure scores and protected against the loss of hippocampal neurons, indicating its potential as an antiepileptic agent.

Ibuprofen's mechanism of action includes reducing the expression of inflammatory mediators like COX-2 and interleukin-18, as well as altering neuronal excitability, which may contribute to its neuroprotective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibuprofen Exerts Antiepileptic and Neuroprotective Effects in the Rat Model of Pentylenetetrazol-Induced Epilepsy via the COX-2/NLRP3/IL-18 Pathway. Liu, R., Wu, S., Guo, C., et al.[2021]

Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and piroxicam can enhance the anticonvulsive activity of certain antiepileptic drugs, particularly valproate magnesium, without affecting their plasma levels.

While NSAIDs improve the protective effects against seizures, using them with valproate may lead to increased side effects, highlighting the need for careful consideration in treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of non-steroidal anti-inflammatory drugs on the anticonvulsive activity of valproate and diphenylhydantoin against maximal electroshock-induced seizures in mice. Kaminski, R., Kozicka, M., Parada-turska, J., et al.[2015]

Ibuprofen abuse, particularly through products like Nurofen Plus, can lead to serious complications such as hypokalaemia, which is a low potassium level in the blood.

This case highlights that ibuprofen is often overlooked in standard toxicology screenings, suggesting that it should be considered as a potential cause of hypokalaemia in patients with unexplained symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypokalaemia in ibuprofen and codeine phosphate abuse. Dyer, BT., Martin, JL., Mitchell, JL., et al.[2020]

In a study of 20 patients with severe epilepsy, the addition of nifedipine to their antiepileptic therapy resulted in only 2 patients experiencing improved seizure control, while 2 others had worsened seizure control.

Side effects were common, with 6 patients reporting issues such as headaches and dizziness, leading to discontinuation of the drug in 2 cases, highlighting the need for caution when considering nifedipine as an adjunct treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nifedipine as an add-on drug in the management of refractory epilepsy. Sander, JW., Trevisol-Bittencourt, PC.[2019]

Convulsant doses of pentetrazole increased levels of certain inflammatory compounds (PGF2 alpha, PGE2, and TXB2) in the mouse brain, indicating a link between inflammation and seizure activity.

Non-steroidal anti-inflammatory drugs (NSAIDs) like indomethacin, flurbiprofen, and diclofenac effectively inhibited the increase of these compounds and also lowered the convulsive threshold, suggesting that they may help manage seizures by reducing inflammation in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lowering of the convulsive threshold by non-steroidal anti-inflammatory drugs. Steinhauer, HB., Hertting, G.[2019]

In a study involving conscious rats subjected to 20 sessions of pentylenetetrazol to induce seizures, pretreatment with paracetamol significantly reduced seizure activity, indicating its potential efficacy in managing seizure episodes.

While some NSAIDs like mefenamic acid showed varying effects on seizure activity, none of the pretreatments prevented the long-term development of seizure susceptibility, suggesting that while NSAIDs can influence immediate seizure responses, they do not alter the underlying process of epileptogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuation of epileptogenesis by nonsteroidal anti-inflammatory drugs in the rat. Wallenstein, MC.[2019]

Two dihydropyridine derivatives (A and B) demonstrated significant anticonvulsant effects in mice, as shown by their ability to reduce seizure activity in both pentylenetetrazole (PTZ) and electroshock tests.

While both compounds showed efficacy, they were less effective than established anticonvulsants like phenytoin and valproate, suggesting they may be useful for treating certain types of epilepsy, such as petit mal and grand mal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of anticonvulsant effect of two novels 4-[1-(4-fluorobenzyl)- 5-imidazolyl] dihydropyridine derivatives in mice. Hadizadeh, F., Rahimi, B., Taghiabadi, E., et al.[2021]

Nifedipine was used as an additional treatment for three patients with uncontrolled epilepsy, suggesting potential benefits in managing this condition.

The study highlights the exploration of nifedipine's role in epilepsy management, although specific outcomes and efficacy details are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nifedipine as a coadjuvant drug in the treatment of uncontrolled epilepsy: a preliminary report]. Rotta, NT., Ohlweiler, L., Lago, IS.[2019]

In a study involving 48 rats, ibuprofen was found to significantly reduce seizure activity induced by pentylenetetrazol, as evidenced by lower spike percentages and improved onset times for myoclonic jerks.

The research also indicated that ibuprofen administration led to lower levels of prostaglandin F2 alpha in the brain compared to control groups, suggesting a potential mechanism for its antiepileptic effects, while highlighting the need for further studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effects of Ibuprofen on Pentylenetetrazol-induced Convulsion. Durankuş, F., Şenkal, E., Sünnetçi, E., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5064857/

Anti-inflammatory small molecules to treat seizures and epilepsy Some COX-2 inhibitors, if not all, appear to confer anticonvulsant effects and reduce neuronal injury developing after SE when administered ...

2. researchgate.net researchgate.net/publication/385048737_The_use_of_ibuprofen_as_an_anti-seizure_medication_a_systematic_review

(PDF) The use of ibuprofen as an anti-seizure medication Our study is the first to demonstrate the beneficial effects of ibuprofen on seizures through behavioral, EEG, and PGF2α brain assessments.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11795576/

The Anticonvulsant Effect of Nonsteroidal Anti ... Previous studies in different epilepsy models showed that pretreatment with NSAIDs such as Ibuprofen or Indomethacin had anticonvulsant effects.

4. sciendo.com sciendo.com/pdf/10.2478/joepi-2024-0001

The use of ibuprofen as an anti-seizure medication In animal models of seizures, ibuprofen has an antiseizure effect by reducing the number, grade, and duration of seizures. Key words: antiseizure • epilepsy • ...

5. openaccess.sgul.ac.uk openaccess.sgul.ac.uk/108264/1/Hitchings%20-%20Drugs%20that%20lower%20the%20seizure%20threshold%20-%20Author%20final%20version.pdf

Drugs that lower the seizure threshold 22,23 By contrast, ibuprofen and paracetamol have not been shown to lower the seizure ... Seizure risk associated with neuroactive drugs: data from the WHO.

6. epilepsy.com epilepsy.com/what-is-epilepsy/seizure-triggers/over-counter-medications

Over-the-Counter Medications as a Seizure Trigger Other common medicines (even aspirin in some cases) can increase the unwanted side effects of your seizure medicines or increase seizures.

7. mayoclinic.org mayoclinic.org/drugs-supplements/ibuprofen-oral-route/description/drg-20070602

Ibuprofen (oral route) - Side effects & dosage Other signs may include changes in skin color of the face; very fast but irregular heartbeat or pulse; hive-like swellings on the skin; and ...

8. aesnet.org aesnet.org/otc/otc-medications-and-epilepsy--pain-relief-analgesics

OTC Pain References - American Epilepsy Society Phenytoin Levels: Ibuprofen can increase plasma levels of phenytoin, heightening the risk of phenytoin-related side effects such as ataxia and nystagmus.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12472944/

Pharmacovigilance Insights into Ibuprofen's Neuropsychiatric ... By comparison with ketoprofen, acetylsalicylic acid, and diclofenac, ibuprofen presented a higher probability of reporting psychiatric and behavioral symptoms.

10. epilepsy.com epilepsy.com/stories/flu-season-do-you-need-worry-about-medication-interactions

Flu Season & Medication Interactions Ibuprofen (Advil and Motrin) is another good drug for fever and pain but it can cause side effects like dizziness and difficulty walking when used in ...