Treating Postictal Symptoms Using Ibuprofen and Nifedipine

An Initial Clinical Study to Treat Postictal Symptoms

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.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy; Epilepsies, Partial
• Intervention / Treatment: Drug: Placebo; Drug: Ibuprofen; Drug: Nifedipine

Detailed Description

Immediately following seizures, brain blood flow is significantly reduced for approximately one hour and is located to the brain area where the seizure originated. This may contribute to symptoms that patients experience immediately following seizures and in between seizures.

Animal studies have shown that that giving anti-inflammatory drugs (e.g., ibuprofen) and blood pressure medications (e.g., nifedipine) prevents the hypoperfusion and behavioural impairments seen in animals immediately following seizures. Thus, two classes of inexpensive and well-tolerated drugs - already in clinical use - have been identified that can be tested in humans to prevent the serious consequences that follow seizures.

The investigators will study 90 subjects admitted to hospital for epilepsy investigations. The investigators will randomly divide the patients into three treatment groups (30 patients each). Patients will receive either placebo, ibuprofen, or nifedipine while in hospital. The effect of each of these treatments on the severity of hypoperfusion and neurological deficits that follows seizures will then be assessed.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Paolo Federico, MD, PhD; Phone Number: =1.403.944.4091; Email: pfederic@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N T29
      • Recruiting
      • Foothills Medical Centre
      • Contact: Paolo Federico, MD, PhD; Phone Number: +1.403.944.4091; Email: pfederic@ucalgary.ca
    • Calgary, Alberta, Canada, T3M 1M4
      • Recruiting
      • South Health Campus
      • Contact: Paolo Federico, MD, PhD; Phone Number: 403.944.4091; Email: pfederic@ucalgary.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age > 16 yrs, frequent seizures (>1 per week) and cognitive ability sufficient to complete neuropsychological testing.

Exclusion Criteria:

• multiple seizure onset zones, contraindications to CT or MR imaging, any contraindication to ibuprofen or nifedipine, as well as current or recent (< 2 months) exposure COX-2 inhibitor or calcium channel blocker.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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.	Drug: Placebo; Sugar pill to be prepared in a tablet that is not distinguishable from ibuprofen or nifedipine tablet.
Experimental: Ibuprofen; 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.	Drug: Ibuprofen; Ibuprofen to be prepared in a tablet that is not distinguishable from nifedipine or placebo tablet.; Other Names: Advil headache & migraine extra strength; DIN 02467658
Experimental: Nifedipine; 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.	Drug: Nifedipine; Nifedipine to be prepared in a tablet that is not distinguishable from ibuprofen or placebo tablet.; Other Names: Adalat XL 20 mg, DIN 02237618; Adalat XL 30 mg, DIN 02155907

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postictal blood flow	Change in cerebral blood flow following seizures, relative to baseline. It will be measured by CT perfusion or ASL MRI.	5 - 40 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological performance - Picture Sequence Memory Test	For all Cognition Domain tests, three standardized scores are provided: An uncorrected score comparing the test-taker to all individuals in the NIH Toolbox normative sample (mean = 100, SD = 15);; An age-corrected score that compares the test-taker to NIH Toolbox age-matched individuals (mean = 100, standard deviation = 15); and; A fully-corrected T-score that adjusts for key demographic variables including age, sex, race/ethnicity, and educational attainment (mean = 50, standard deviation = 10). Measure = Picture sequence memory Construct = Episodic memory Scale ranges: uncorrected score (mean = 100, SD = 15).; age-corrected score (mean = 100, SD = 15).; fully-corrected T-score (mean = 50, SD = 10). For this test, a greater standardized score indicates better episodic memory.	5 - 40 days
Neuropsychological performance - Flanker Inhibitory Control and Attention Test	Measure = Flanker Inhibitory Control and Attention Test Construct = Executive Function & Attention Scale ranges: uncorrected score (mean = 100, standard deviation = 15). Higher score is better; age-corrected score (mean = 100, standard deviation = 15). Higher score is better.; fully-corrected T-score (mean = 50, standard deviation = 10). Higher score is better. For this test, a higher raw or standardized score indicates greater inhibitory control and attention.	5 - 40 days
Neuropsychological performance - List Sorting Working Memory Test	Measure = List Sorting Working Memory Test Construct = Working Memory Scale ranges: uncorrected score (mean = 100, standard deviation = 15). Higher score is better; age-corrected score (mean = 100, standard deviation = 15). Higher score is better.; fully-corrected T-score (mean = 50, standard deviation = 10). Higher score is better. For this test, a greater raw or standardized score indicates better episodic memory.	5 - 40 days
Neuropsychological performance - Picture Vocabulary Test	Measure = Picture Vocabulary Test Construct = Language Scale ranges: uncorrected score (mean = 100, standard deviation = 15). Higher score is better; age-corrected score (mean = 100, standard deviation = 15). Higher score is better.; fully-corrected T-score (mean = 50, standard deviation = 10). Higher score is better. For this test, a higher standardized score indicates greater general vocabulary knowledge.	5 - 40 days
Neuropsychological performance- Oral Reading Recognition Test	Measure = Oral Reading Recognition Test Construct = Language Scale ranges: uncorrected score (mean = 100, standard deviation = 15). Higher score is better; age-corrected score (mean = 100, standard deviation = 15). Higher score is better.; fully-corrected T-score (mean = 50, standard deviation = 10). Higher score is better. For this test, a higher standardized score indicates a greater ability to read aloud.	5 - 40 days
Neuropsychological performance - Dimensional Change Card Sort Test	Measure = Dimensional Change Card Sort Test Construct = Executive function Scale ranges: uncorrected score (mean = 100, standard deviation = 15). Higher score is better; age-corrected score (mean = 100, standard deviation = 15). Higher score is better.; fully-corrected T-score (mean = 50, standard deviation = 10). Higher score is better. For this test, a greater raw or standardized score indicates greater cognitive flexibility.	5 - 40 days
Neuropsychological performance - Pattern Comparison Processing Speed Test	Measure = Pattern Comparison Processing Speed Test Construct = Processing Speed Scale ranges: uncorrected score (mean = 100, standard deviation = 15). Higher score is better; age-corrected score (mean = 100, standard deviation = 15). Higher score is better.; fully-corrected T-score (mean = 50, standard deviation = 10). Higher score is better. For this test, a greater raw or standardized score indicates faster processing speed.	5 - 40 days
Psychological well-being	The Psychological Well-Being measure assesses a subjective and experiential aspect of pleasure and positive affect, as well as fulfillment and purpose. Psychological Well-being composite scores are generated as the weighted average of the uncorrected standardized score (T scores; mean = 50, SD = 10) obtained from each subdomain: Positive Affect Construct = This portion assesses positive affect, or feelings of a pleasurable engagement with the environment, using a positive affect survey. Higher scores = more positive affect. Life Satisfaction Construct = This portion assesses how the participant evaluates their life, in terms of whether they like it or not, using a life satisfaction survey. Higher scores = greater life satisfaction. Meaning and Purpose Construct = This portion evaluates the degree to which the participant feels their life matters or makes sense. Higher scores = greater sense of meaning and purpose.	5 - 40 days
Social Relationships	The Social Relationships measure assesses the participants social network structure, extent, and quality. Composite social satisfaction composite scores are generated as the weighted average of the T-scores (mean = 50, SD = 10) from the subdomains, with loneliness and perceived rejection reverse-coded. Perceived Social Support Construct = This portion evaluates the degree to which the participant feels their life matters or makes sense. Higher scores = greater sense of meaning and purpose. Companionship Construct = This portion assesses self-reported perceptions of the participant has companions to interact with and perceptions of being alone or lonely. Higher scores = higher perceived friendship or more loneliness. Social Distress Construct = This portion evaluates the degree to which the participant feels their life matters or makes sense. Higher scores = greater perceived hostility and rejection.	5 - 40 days
Stress and Self-Efficacy Relationships	The Stress and Self-Efficacy measure assesses the individual's perception of life events and their relationships as well as their perceived coping skills. Stress and self-efficacy composite scores are generated as the weighted average of the T-scores (mean = 50, SD = 10) from the subdomains Perceived Stress Construct = This portion evaluates the participants perceived stress. Higher scores = greater perceived stress. Self-Efficacy Construct = This portion assesses self-efficacy, or the participants belief in their capacity to manage and have control over events. Higher scores = more general self-efficacy.	5 - 40 days
Negative affect	composite scores are generated as the weighted average of the T-scores from the subdomains. Negative affect includes the following subdomains: Anger Construct = This portion assesses attitudes of hostility and cynicism. Higher scores = higher levels of anger. Fear Construct = This portion assesses the participants perception of threat and autonomic arousal associated with fear. Higher scores = higher levels of fear. Sadness Construct = This portion assesses the participants feelings of sadness, or their low levels of positive affect or low mood. Higher scores = more sadness.	5 - 40 days

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Paolo Federico, MD, PhD, University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: May 10, 2019
• First Posted (Actual): May 14, 2019

Study Record Updates

• Last Update Posted (Actual): November 16, 2022
• Last Update Submitted That Met QC Criteria: November 15, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Postictal; Blood flow
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Ibuprofen; Nifedipine
• Other Study ID Numbers: TPS-1.0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No