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Treating Postictal Symptoms Using Ibuprofen and Nifedipine

Primary Purpose

Epilepsy, Epilepsies, Partial

Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Ibuprofen
Nifedipine
Placebo
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Postictal, Blood flow

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Foothills Medical CentreRecruiting
  • South Health CampusRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

Ibuprofen

Nifedipine

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Postictal blood flow
Change in cerebral blood flow following seizures, relative to baseline. It will be measured by CT perfusion or ASL MRI.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
April 11, 2019
Last Updated
November 15, 2022
Sponsor
University of Calgary
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1. Study Identification

Unique Protocol Identification Number
NCT03949478
Brief Title
Treating Postictal Symptoms Using Ibuprofen and Nifedipine
Official Title
An Initial Clinical Study to Treat Postictal Symptoms
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2021 (Actual)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
March 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Calgary

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy, Epilepsies, Partial
Keywords
Postictal, Blood flow

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
We will study 90 subjects admitted to hospital for epilepsy investigations. We will randomly divide the patients into three treatment groups (30 patients each). They will receive either placebo, ibuprofen, or nifedipine while in hospital. We will then determine the effect of each of these treatments on the severity of hypoperfusion and neurological deficits that follows their seizures.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The UofC Clinical Research Unit, which has no contact with patients or clinicians, will prepare the concealed randomization schedule and the randomization tool. Our research pharmacy will prepare three identical tablets to be given to each subject. The participant, care provider, investigators, and outcomes assessors will be blinded to treatment
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Ibuprofen
Arm Type
Experimental
Arm Description
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.
Arm Title
Nifedipine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ibuprofen
Other Intervention Name(s)
Advil headache & migraine extra strength; DIN 02467658
Intervention Description
Ibuprofen to be prepared in a tablet that is not distinguishable from nifedipine or placebo tablet.
Intervention Type
Drug
Intervention Name(s)
Nifedipine
Other Intervention Name(s)
Adalat XL 20 mg, DIN 02237618, Adalat XL 30 mg, DIN 02155907
Intervention Description
Nifedipine to be prepared in a tablet that is not distinguishable from ibuprofen or placebo tablet.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Sugar pill to be prepared in a tablet that is not distinguishable from ibuprofen or nifedipine tablet.
Primary Outcome Measure Information:
Title
Postictal blood flow
Description
Change in cerebral blood flow following seizures, relative to baseline. It will be measured by CT perfusion or ASL MRI.
Time Frame
5 - 40 days
Secondary Outcome Measure Information:
Title
Neuropsychological performance - Picture Sequence Memory Test
Description
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.
Time Frame
5 - 40 days
Title
Neuropsychological performance - Flanker Inhibitory Control and Attention Test
Description
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.
Time Frame
5 - 40 days
Title
Neuropsychological performance - List Sorting Working Memory Test
Description
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.
Time Frame
5 - 40 days
Title
Neuropsychological performance - Picture Vocabulary Test
Description
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.
Time Frame
5 - 40 days
Title
Neuropsychological performance- Oral Reading Recognition Test
Description
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.
Time Frame
5 - 40 days
Title
Neuropsychological performance - Dimensional Change Card Sort Test
Description
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.
Time Frame
5 - 40 days
Title
Neuropsychological performance - Pattern Comparison Processing Speed Test
Description
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.
Time Frame
5 - 40 days
Title
Psychological well-being
Description
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.
Time Frame
5 - 40 days
Title
Social Relationships
Description
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.
Time Frame
5 - 40 days
Title
Stress and Self-Efficacy Relationships
Description
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.
Time Frame
5 - 40 days
Title
Negative affect
Description
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.
Time Frame
5 - 40 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Paolo Federico, MD, PhD
Phone
=1.403.944.4091
Email
pfederic@ucalgary.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paolo Federico, MD, PhD
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
Foothills Medical Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N T29
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paolo Federico, MD, PhD
Phone
+1.403.944.4091
Email
pfederic@ucalgary.ca
Facility Name
South Health Campus
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3M 1M4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paolo Federico, MD, PhD
Phone
403.944.4091
Email
pfederic@ucalgary.ca

12. IPD Sharing Statement

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Treating Postictal Symptoms Using Ibuprofen and Nifedipine

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