Photosensitive EpilepsyPhase 4NCT00609245

Effect of Valproic Acid Concentration on Photic Response

A Phase 4 study testing Valproic Acid in people with Photosensitive Epilepsy, run by Vanderbilt University Medical Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

We are trying to learn if small changes in the amount of a valproate in the blood (given through an IV) will change the way the brain reacts to flashing lights. Read more about this study

Who is it for?: Ages 15 to 65 years
Conditions the study is for: Photosensitive Epilepsy
What is being tested?: Valproic Acid
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 13 participants
Where: 2 sitesUnited States
Study dates: Dec 2007to Dec 2008
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 15 to 65 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Male or female patients
Aged 15 to 65 years
Patients with a diagnosis of epilepsy for which they are either taking up two AEDs, not including VPA/divalproex, or no AEDs
Patients with a reproducible IPS-induced photo-paroxysmal responses of at least 7 SPR-EEG units as measured at two different time points in the day (pm screening Study Visit 1 and am of Visit 2).
Are in good health (with the exception of epilepsy).
Able and willing to provide written informed consent.

Who cannot join

Patients not exhibiting a photo-paroxysmal-EEG response
Patients with active psychogenic seizures
Women who are pregnant or lactating
Women of reproductive potential who do not agree to use effective birth-control methods during the study and for one week after receiving study drug.
Patients taking any dosage form of VPA/divalproex within 4 weeks prior to the study
Patients taking more than two concomitant AEDs

Show all 17Show fewer

Patients with any clinically significant laboratory abnormality, which in the opinion of the investigator, will exclude the patient from the study
Patients who are suffering from active liver disease indicated by abnormal liver function tests greater than three times the upper limit of normal (AST and ALT), patients with porphyria, or patients with a family history of severe hepatic dysfunction
Patients with a history of alcoholism, drug abuse, or drug addiction (within the past 12 months)
Patients with a history of sensitivity or allergic reaction to valproate / divalproex
Patients who have a medical history which would contraindicate sodium valproate (VPA) administration
Patients who have participated in any other trials involving an investigational product or device within 30 days of screening.
Patients with clinically significant ECG abnormalities, as judged by the PI, at screening visit
Patients with such poor intravenous access that the insertion of two intravenous catheters (one for sodium valproate infusion and one, in a contralateral arm vein, for serial blood sampling) for a 12-hour period is not possible.
Patients who received benzodiazepines within one week of study initiation
Status epilepticus within one year of screening
Generalized tonic-clonic seizure within 24 hours of photic stimulation procedure

Trial locations and contacts

2 sites in 1 country.

United States2 sites

The Comprehensive Epilepsy Care Center for Children & Adults
Chesterfield, Missouri, 63017
Vanderbilt University
Nashville, Tennessee, 37232

Other trials in United States

About this study

Official title: Effect of Small Changes in Plasma Valproic Acid Concentration on the Photoparoxysmal Response

We are trying to learn if small changes in the amount of a valproate in the blood (given through an IV) will change the way the brain reacts to flashing lights.

Read the detailed description

Photosensitive epilepsy is a form of epilepsy that is considered to have a genetic basis in most instances. It is a reflex type of epilepsy. Patients with this condition exhibit epileptic activity patterns (called photoparoxysmal response-PPR) on their EEG during intermittent photic stimulation with certain flash frequencies.

Specific Aims

To determine the extent of the pharmacodynamic effect of small changes in total and free VPA concentration via constant infusion of intravenous sodium valproate within the same photosensitive epilepsy patient.
To determine the change in total and free VPA concentration required to achieve maximal effect on PPR in patients with photosensitive epilepsy.

Hypothesis

Valproic acid (VPA) demonstrates differential pharmacodynamic effect on PPR with small changes in VPA concentration (5-20 mg/L changes in total, or 0.5 to 2 mg/L changes in free VPA) within the same patient. In essence, the VPA concentration-response curve in patients with photosensitive epilepsy is relatively steep.
Intravenously-administered VPA will demonstrate a reduction in standard photosensitive range (SPR) or abolition of PPR for at least 80% of patients studied, when the entire range of free VPA concentrations is considered.

Photosensitivity, defined as a PPR on intermittent photic stimulation (IPS), is found in approximately 5% of all epileptic patients. Markedly photosensitive patients are usually sensitive to IPS within clearly defined limits of flash frequency (mostly between 10-30 Hz). This photosensitivity range, the difference between the highest and lowest flash rates that consistently elicit a photoparoxysmal response (PPR), can be used as a quantitative measure of photosensitivity.

Administration of some antiepileptic drugs (AEDS) can diminish or even abolish PPR. With a standard set of tested frequencies, a standard photosensitive range (SPR) can be used to measure drug effect on photosensitivity. Combined with blood level monitoring, the model offers information about actual pharmacodynamic effect as measured with IPS related to the changes in blood levels.

The standardized IPS procedure includes delivery of short (5 second-) trains of flashes. The stimulation starts with the lowest frequencies (which usually do not produce a PPR) only up to the limits of the photosensitivity range (the threshold frequencies for which the patient shows an epileptiform EEG response). After that the stimulation starts again with the highest frequencies (which also do not produce a PPR) down to the frequency that produces a definite PPR.

The photic stimulator will be manually controlled for all stimulations in order to abort the stimulation when a clear PPR is elicited. With all stimulations, there is simultaneous recording of the EEG and direct observation of the patient for clinical changes. With all the safety measures in place, the likelihood of provoking prominent clinical seizures is extremely low.

Conditions: Photosensitive Epilepsy
Being tested: Valproic Acid, Placebo
Keywords: epilepsy, photosensitive, valproic acid
Medical subject headings: Epilepsy, Reflex, Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Valproic AcidDrug
Also called Depacon
The investigators will utilize intravenous sodium valproate at visit 3. Dosage will be individualized to each patient's body weight, age, and hepatic-enzyme-inducing status. Intravenous VPA dose predictions will be based upon population VPA pharmacokinetic parameters (Dutta 2003).
PlaceboDrug
Also called Normal Saline (NS) and 5% Dextrose in water (D5W)
Each patient will have a placebo-infusion (with 0.9% NS or D5W) of 12-hour duration at visit 2.

Study groups in NCT00609245
Study group	Role	What they receive
Placebo then Valproic Acid (VPA)	Experimental	all patients will have placebo on day 1 and VPA infusion on day 2 Receives: Drug: Valproic Acid; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Difference in SPR During Placebo and VPA Infusions
standard photosensitive range (SPR) Each participant is exposed to intermittent photic stimulation at 14 predetermined frequencies in order to detect changes in response around typical upper and lower frequency thresholds (e.g., 2 Hz, 5 Hz, 8Hz, 10 Hz, etc.). Each flash frequency that elicits a photosensitive response is considered one "step", and the result is transformed into a metric called the standardized photosensitive range (SPR). The SPR ranges from 0 to 14, where each point represents the number of flash frequencies that elicited a photosensitive response.
Measured: At the start of EEG monitoring/drug infusion, and on an hourly basisfor 12 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2007Dec 2008

First posted6 Feb 2008 (estimated)
Study startDec 2007
Primary completionDec 2008
Study completionDec 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Photosensitive EpilepsyStudies of the same condition, open and under way.
More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00609245
Sponsor's protocol ID: IRB# 070849
Status last verified: May 2017
First submitted: 1 Feb 2008
Last updated: 14 Jun 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect of Small Changes in Plasma Valproic Acid Concentration on the Photoparoxysmal Response
ClinicalTrials.gov ID: NCT00609245
Acronym / sponsor ID: IRB# 070849
Conditions: Photosensitive Epilepsy
Keywords: epilepsy, photosensitive, valproic acid
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Vanderbilt University Medical CenterUniversity, hospital or other
Collaborators: Abbott
Study start: Dec 2007
Primary completion: Dec 2008 (actual)
Study completion: Dec 2008 (actual)
First posted: 6 Feb 2008 (estimated)
Results: Posted 14 Jun 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

We are trying to learn if small changes in the amount of a valproate in the blood (given through an IV) will change the way the brain reacts to flashing lights.

Detailed description

Specific Aims

To determine the extent of the pharmacodynamic effect of small changes in total and free VPA concentration via constant infusion of intravenous sodium valproate within the same photosensitive epilepsy patient.
To determine the change in total and free VPA concentration required to achieve maximal effect on PPR in patients with photosensitive epilepsy.

Hypothesis

Valproic acid (VPA) demonstrates differential pharmacodynamic effect on PPR with small changes in VPA concentration (5-20 mg/L changes in total, or 0.5 to 2 mg/L changes in free VPA) within the same patient. In essence, the VPA concentration-response curve in patients with photosensitive epilepsy is relatively steep.
Intravenously-administered VPA will demonstrate a reduction in standard photosensitive range (SPR) or abolition of PPR for at least 80% of patients studied, when the entire range of free VPA concentrations is considered.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Placebo then Valproic Acid (VPA)	Experimental	Drug: Valproic Acid, Drug: Placeboall patients will have placebo on day 1 and VPA infusion on day 2

Who may qualify

Ages: 15 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (6 listed)

Male or female patients
Aged 15 to 65 years
Patients with a diagnosis of epilepsy for which they are either taking up two AEDs, not including VPA/divalproex, or no AEDs
Patients with a reproducible IPS-induced photo-paroxysmal responses of at least 7 SPR-EEG units as measured at two different time points in the day (pm screening Study Visit 1 and am of Visit 2).
Are in good health (with the exception of epilepsy).

Key exclusion criteria (17 listed)

Patients not exhibiting a photo-paroxysmal-EEG response
Patients with active psychogenic seizures
Women who are pregnant or lactating
Women of reproductive potential who do not agree to use effective birth-control methods during the study and for one week after receiving study drug.
Patients taking any dosage form of VPA/divalproex within 4 weeks prior to the study

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Valproic AcidAlso: DepaconThe investigators will utilize intravenous sodium valproate at visit 3. Dosage will be individualized to each patient's body weight, age, and hepatic-enzyme-inducing status. Intravenous VPA dose predictions will be based upon population VPA pharmacokinetic parameters (Dutta 2003).	Drug	Placebo then Valproic Acid (VPA)
PlaceboAlso: Normal Saline (NS) and 5% Dextrose in water (D5W)Each patient will have a placebo-infusion (with 0.9% NS or D5W) of 12-hour duration at visit 2.	Drug	Placebo then Valproic Acid (VPA)

Primary outcome

Difference in SPR During Placebo and VPA Infusions
Time frame: At the start of EEG monitoring/drug infusion, and on an hourly basisfor 12 hours
standard photosensitive range (SPR) Each participant is exposed to intermittent photic stimulation at 14 predetermined frequencies in order to detect changes in response around typical upper and lower frequency thresholds (e.g., 2 Hz, 5 Hz, 8Hz, 10 Hz, etc.). Each flash frequency that elicits a photosensitive response is considered one "step", and the result is transformed into a metric called the standardized photosensitive range (SPR). The SPR ranges from 0 to 14, where each point represents the number of flash frequencies that elicited a photosensitive response.

Results and safety

Results posted to the registry on 14 Jun 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Valproate Infusion	13	12

Primary outcome: Difference in SPR During Placebo and VPA Infusions

Time frame: At the start of EEG monitoring/drug infusion, and on an hourly basisfor 12 hours. Mean (Full Range). Unit: standard photosensitive range (SPR)

Measure	Placebo n = 12	Valproic Acid n = 12
Value	15.917 (14.739 to 17.431)	14.609 (12.903 to 17.124)

Placebo: p = 0.016, ANOVA

Population analysed: 1 patient did not complete infusion of Valproic Acid due to Adverse Event. This patient was not included in final analysis.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Valproic Acid	1 of 13 (7.7%)	0 of 13 (0%)	Not reported
Placebo	0 of 13 (0%)	0 of 13 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Bassel Abou-Khalil, MD principal investigator

Vanderbilt University

William Rosenfeld, MD principal investigator

The Comprehensive Epilepsy Care Center for Children & Adults

Dorothee Kasteleijn-Nolst Trenite, MD, PhD principal investigator

The Comprehensive Epilepsy Care Center for Children & Adults

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Valproic Acid in people with Photosensitive Epilepsy, run by Vanderbilt University Medical Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Difference in SPR During Placebo and VPA Infusions (time frame: At the start of EEG monitoring/drug infusion, and on an hourly basisfor 12 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00609245.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2017.