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

Trial Summary

What is the purpose of this trial?

This study will evaluate the effect of ibuprofen or nifedipine on post-seizure hypoperfusion and neurological deficits in patients with epilepsy. One group will receive ibuprofen, another will receive nifedipine, and anther placebo.

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.

What data supports the idea that Ibuprofen + Nifedipine for Post-Seizure Symptoms in Epilepsy is an effective drug?

The available research shows that ibuprofen alone has some beneficial effects on seizures in animal studies. For example, ibuprofen reduced seizure scores and protected brain cells in rats with induced epilepsy. It also enhanced the effectiveness of other epilepsy drugs in mice. However, there is no specific data on the combination of ibuprofen and nifedipine for post-seizure symptoms in epilepsy. The research on nifedipine alone is limited, with only a preliminary report on its use in a few patients with uncontrolled epilepsy. Therefore, while ibuprofen shows promise, more research is needed to confirm the effectiveness of the combination with nifedipine for this condition. ^{1 2 3 4 5}

What safety data exists for using Ibuprofen and Nifedipine in treating post-seizure symptoms in epilepsy?

The safety data for Ibuprofen and Nifedipine in treating post-seizure symptoms in epilepsy is limited. Ibuprofen has been shown to have beneficial effects on seizures in animal studies, suggesting it can be used safely for epilepsy without inducing seizures. However, high doses of Ibuprofen can be lethal, as seen in rat studies. Nifedipine, a dihydropyridine derivative, has shown anticonvulsant activity in animal models, but its effects are less potent than other anticonvulsants like phenytoin and valproate. Overall, more clinical studies are needed to confirm the safety and efficacy of this combination for post-seizure symptoms in epilepsy. ^{1 3 6 7 8}

Is the drug Ibuprofen, Nifedipine, Placebo a promising treatment for post-seizure symptoms in epilepsy?

Ibuprofen shows promise as a treatment for epilepsy because it can reduce seizures and protect brain cells, according to studies on rats. Nifedipine, however, has shown limited success in improving seizure control in humans. ^{1 2 3 4 9}

Research Team

Paolo Federico, MD, PhD

Principal Investigator

University of Calgary

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Germany pubmed.ncbi.nlm.nih.gov

[Nifedipine as a coadjuvant drug in the treatment of uncontrolled epilepsy: a preliminary report]. [2019]

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

Beneficial Effects of Ibuprofen on Pentylenetetrazol-induced Convulsion. [2021]

4. United States 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. [2021]

5. Netherlands 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. [2015]

6. Iran pubmed.ncbi.nlm.nih.gov

Evaluation of anticonvulsant effect of two novels 4-[1-(4-fluorobenzyl)- 5-imidazolyl] dihydropyridine derivatives in mice. [2021]

7. India pubmed.ncbi.nlm.nih.gov

Hypokalaemia in ibuprofen and codeine phosphate abuse. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Lowering of the convulsive threshold by non-steroidal anti-inflammatory drugs. [2019]

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

Nifedipine as an add-on drug in the management of refractory epilepsy. [2019]