Epilepsies, PartialPhase 4NCT05273398
Effects of Diazepam on RNS Detections
A Phase 4 study testing nasal diazepam in people with Epilepsies, Partial, run by University of Cincinnati at 1 site in United States.
Trial summary
To assess the magnitude and duration of reduction in RNS recorded Detections and Long Episodes following intranasal administration of Valtoco®. All participants will have been implanted and treated with an RNS system for clinical purposes and regularly upload Detection and Long Episode data on a regular basis as part… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epilepsies, Partial
- What is being tested?
- nasal diazepam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2022to 10 Nov 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Inclusion Criteria (participants must meet all Inclusion Criteria)
- Age 18 or above
- Participant will weigh >50 Kg.
- RNS will have been implanted for usual treatment for at least 3 months. Detection settings will be stable at least 30 days.
- No changes in AED dosages, VNS settings (if participant has VNS) or RNS detection or stimulation parameters 30 days before and during the study. However, patients with newer VNS models that have tachycardia detection will be excluded because of the variability of the stimulations, which could affect RNS Detections. If the VNS device that uses tachycardia detection can be inactivated, the patient would not be excluded from participating in the study.
- Minimum mean rate of Detections of 5 (NUMBER CHANGED) per hour during the hours of 9 AM to 5 PM, and no fewer than 2 (NUMBER CHANGED) Detections in any hour between 9 AM and 5 PM in the pre-dose baseline observation period. Pre-dose baseline observation period will be 7 days in duration, from day -7 to day 0 prior to dosing.
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- Participant must meet criteria for Detection variability based on historical Detections. No more than 97% (NUMBER CHANGED) change in highest to lowest hour detection during the 9 AM to 5 PM observation period OF A SINGLE DAY. Calculation will be (highest hourly detection rate - lowest hourly detection rate)/highest hourly detection rate= <0.97 (NUMBER CHANGED). For example: highest hourly detection rate = 1000; lowest hourly detection rate = 300, (1000-300)/1000 = 0.7, and this patient would meet qualifying criteria.
- If the participant fails the minimal mean Detection rate criteria or Detection variability criteria during the screening period, one additional screening period for RNS Detections may take place a minimum of one week later.
- If the participant fails screening due to a clinical seizure in the 96 hours prior to dosing, two additional screening periods for Detection and seizures may be undertaken.
- Focal epilepsy consistent with ILAE criteria supported by either EEG or MRI data and meets ILAE definition of refractory epilepsy.
- May be on stable prescribed dose of Selective Serotonin Reuptake Inhibitor (SSRI), Serotonin-Norepinephrine Reuptake Inhibitor (SNRI), or atypical antipsychotic for at least 3 months
- Optimal candidates will have temporal lobe RNS implantation, but extra-temporal implantation is acceptable if minimal Detection rate criteria are met.
Who cannot join
- Pregnancy; every woman of childbearing age will be asked at every visit, "Do you think that you might be pregnant?" If yes, a pregnancy test will be administered. Any woman with a positive test will be excluded from participation.
- Not competent to sign consent
- Any history of substance abuse within the previous 2 years.
- Cannabidiol as EpidiolexR on a stable dose, will be the only allowed cannabinoid. Subjects with recreational or medicinal use of marijuana, cannabinoids and/or derivatives in the prior 30 days will be excluded.
- Current chronic opioid use.
- History of poor medication compliance as judged by the investigator
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- Any medical or psychiatric condition that the investigator believes would impair reliable participation in the trial
- Subject is participating or has participated in an investigational product/device trial currently or in the preceding 30 days.
- Subject has been diagnosed with only psychogenic or non-epileptic seizures.
- Use of rescue benzodiazepines less than two weeks before baseline detection rate assessment begins. Stable doses of a prescribed benzodiazepine for 30 days prior to study entry is permitted.
- Benzodiazepines used intermittently or on an as needed basis for sleep will not be allowed for the 7 days prior to and 7 days following the Valtoco dose.
- No clinical seizure during the period starting 48 hours before pre-dose baseline observation period begins (i.e., 96 hours before dose is administered) until 48 hours after the Valtoco administration. If a clinical seizure occurs during the 48-hour pre-dose baseline period, the potential participant can be re-screened after one week. If a clinical seizure occurs within 8 hours of dosing, the participant may repeat screening and dose after one week. If a clinical seizure occurs more than 8 hours after dosing, the PI will assess whether the first 8-hour data is sufficient or whether a re-screening and dose should take place.
- A history of allergy to diazepam or midazolam, or any of the ingredients of Valtoco®.
- A history of adverse reaction to diazepam or midazolam that in the opinion of the investigator would jeopardize the health of the participant or interfere with interpretation of study results.
- A history of narrow-angle glaucoma or inadequately treated open-angle glaucoma
- Large variations in RNS detections that in the opinion of the investigator would interfere with the ability to detect a drug effect on detections. Examples may include, but are not limited to, clusters of detections lasting a few days in duration or a high degree of cyclic clusters of detections.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exploratory Open-Label Study of Effects on Responsive Neurostimulator Activity After Intranasal Administration of Single Dose of Valtoco® to People With Epilepsy
To assess the magnitude and duration of reduction in RNS recorded Detections and Long Episodes following intranasal administration of Valtoco®. All participants will have been implanted and treated with an RNS system for clinical purposes and regularly upload Detection and Long Episode data on a regular basis as part of regular clinical treatment. Participants will come to the clinic and be administered a single dose of Valtoco® via nasal spray. RNS recorded Detections and Long Episodes before and after Valtoco® administration will be compared. This is a pilot study, so all outcomes are exploratory.
Read the detailed description
Specific Aim 1: To determine the impact of Valtoco® administration on events recorded by RNS compared to the same time administration of the prior seven days.
Objectives: The investigators will assess the percent change in Detections calculated separately for each hour during the first 8 hours of the post-dose observation period. The number of Detections during each hour of the 8-hour period post dose will be compared to the same hour during the seven comparable 8-hour sessions of the 7-day pre-dose observation period. That is, if the dose was given at 9 AM on day 0, then the mean number of Detections at baseline will be calculated as the mean number of Detections from 9 AM to 10 AM on day -1 through day -7. The percent change in Detections will be calculated as (number of Detections in hour 1 post dose)/(Mean number of Detections in hour 1 on Day -1 through Day -7). The same hourly change will be calculated for each of the 8 hours after dosing. The comparison will be the same hours each day to minimize the hour to hour variability typically seen in these measures.
Hourly histograms generated by the RNS system and stored in the PDMS will be collected. In addition, using "detailed diagnostics" visual analysis of minute-by-minute Detections will be reviewed for obvious patterns of interest for the 8 hours post dosing.
Total number of hours during the 48-hour post-dose observation period where the number of Detections is <50% of the mean hourly Detection rate over the 7-day pre-dose observation period will be calculated.
The number of Long Episodes recorded during the 7-day pre-dose observation period will be compared to the number of Long Episodes during the post-dose 48-hour observation period.
The number of diary-recorded seizures during the post-dose observation period will be recorded.
The investigators will quantify the 2 highest hourly detection rates for the 7-day pre-dose and 48-hour post-dose periods.
The investigators will calculate the number of days required for the daily detection rate to fall within the 90% confidence interval of the 9 am to 5 PM baselines from the 7-day pre-dose baseline.
The investigators will use descriptive statistics for the detection data and Long Episodes for the entire 7-day post dose period.
The investigators will quantify the time course of observable changes in beta activity on the ECoG recorded samples on the day of dosing.
- Conditions
- Epilepsies, Partial
- Being tested
- nasal diazepam
- Keywords
- epilepsy, responsive neurostimulator, diazepam, rescue medication
- Medical subject headings
- Epilepsies, Partial, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nasal diazepamDrug
Also called Nasal diazepam (Valtoco)
Nasal administration of diazepam
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Single arm of treatment Receives: Drug: nasal diazepam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Detections
The investigators will assess the percent change in Detections calculated separately for each hour during the first 8 hours of the post-dose observation period. The number of Detections during each hour of the 8-hour period post dose will be compared to the same hour during the seven comparable 8-hour sessions of the 7-day pre-dose observation period.
Measured: 8 days
Secondary outcomes (3)
Change in hourly histograms
Hourly histograms generated by the RNS system and stored in the PDMS will be collected. In addition, using "detailed diagnostics" visual analysis of minute-by-minute Detections will be reviewed for obvious patterns of interest for the 8 hours post dosing.
Measured: 8 hours
Detection reduction of >50%
Total number of hours during the 48-hour post-dose observation period where the number of Detections is <50% of the mean hourly Detection rate over the 7-day pre-dose observation period will be calculated.
Measured: 9 days
Change in diary recorded seizures
The number of diary-recorded seizures during the post-dose observation period will be recorded.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2022
- Study start1 Mar 2022
- Primary completion10 Nov 2022
- Study completion10 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epilepsies, PartialStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe 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
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 4 subject pilot study
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Privitera, University of Cincinnati
- Investigators
- Michael D Privitera, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05273398
- Sponsor's protocol ID
- 2021-0017
- Status last verified
- Apr 2024
- First submitted
- 17 Feb 2022
- Last updated
- 12 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Detection rates before and after administration of intranasal diazepam will be made available.
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Open-Label Study of Effects on Responsive Neurostimulator Activity After Intranasal Administration of Single Dose of Valtoco® to People With Epilepsy
- ClinicalTrials.gov ID
- NCT05273398
- Acronym / sponsor ID
- 2021-0017
- Conditions
- Epilepsies, Partial
- Keywords
- epilepsy, responsive neurostimulator, diazepam, rescue medication
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 10 Nov 2022 (actual)
- Study completion
- 10 Nov 2022 (actual)
- First posted
- 10 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the magnitude and duration of reduction in RNS recorded Detections and Long Episodes following intranasal administration of Valtoco®. All participants will have been implanted and treated with an RNS system for clinical purposes and regularly upload Detection and Long Episode data on a regular basis as part of regular clinical treatment. Participants will come to the clinic and be administered a single dose of Valtoco® via nasal spray. RNS recorded Detections and Long Episodes before and after Valtoco® administration will be compared. This is a pilot study, so all outcomes are exploratory.
Detailed description
Specific Aim 1: To determine the impact of Valtoco® administration on events recorded by RNS compared to the same time administration of the prior seven days.
Objectives: The investigators will assess the percent change in Detections calculated separately for each hour during the first 8 hours of the post-dose observation period. The number of Detections during each hour of the 8-hour period post dose will be compared to the same hour during the seven comparable 8-hour sessions of the 7-day pre-dose observation period. That is, if the dose was given at 9 AM on day 0, then the mean number of Detections at baseline will be calculated as the mean number of Detections from 9 AM to 10 AM on day -1 through day -7. The percent change in Detections will be calculated as (number of Detections in hour 1 post dose)/(Mean number of Detections in hour 1 on Day -1 through Day -7). The same hourly change will be calculated for each of the 8 hours after dosing. The comparison will be the same hours each day to minimize the hour to hour variability typically seen in these measures.
Hourly histograms generated by the RNS system and stored in the PDMS will be collected. In addition, using "detailed diagnostics" visual analysis of minute-by-minute Detections will be reviewed for obvious patterns of interest for the 8 hours post dosing.
Total number of hours during the 48-hour post-dose observation period where the number of Detections is <50% of the mean hourly Detection rate over the 7-day pre-dose observation period will be calculated.
The number of Long Episodes recorded during the 7-day pre-dose observation period will be compared to the number of Long Episodes during the post-dose 48-hour observation period.
The number of diary-recorded seizures during the post-dose observation period will be recorded.
The investigators will quantify the 2 highest hourly detection rates for the 7-day pre-dose and 48-hour post-dose periods.
The investigators will calculate the number of days required for the daily detection rate to fall within the 90% confidence interval of the 9 am to 5 PM baselines from the 7-day pre-dose baseline.
The investigators will use descriptive statistics for the detection data and Long Episodes for the entire 7-day post dose period.
The investigators will quantify the time course of observable changes in beta activity on the ECoG recorded samples on the day of dosing.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 4 subject pilot study
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: nasal diazepamSingle arm of treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Inclusion Criteria (participants must meet all Inclusion Criteria)
Key exclusion criteria (16 listed)
- Pregnancy; every woman of childbearing age will be asked at every visit, "Do you think that you might be pregnant?" If yes, a pregnancy test will be administered. Any woman with a positive test will be excluded from participation.
- Not competent to sign consent
- Any history of substance abuse within the previous 2 years.
- Cannabidiol as EpidiolexR on a stable dose, will be the only allowed cannabinoid. Subjects with recreational or medicinal use of marijuana, cannabinoids and/or derivatives in the prior 30 days will be excluded.
- Current chronic opioid use.
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 |
|---|---|---|
| nasal diazepamAlso: Nasal diazepam (Valtoco)Nasal administration of diazepam | Drug | Treatment |
Primary outcome
Change in Detections
Time frame: 8 days
The investigators will assess the percent change in Detections calculated separately for each hour during the first 8 hours of the post-dose observation period. The number of Detections during each hour of the 8-hour period post dose will be compared to the same hour during the seven comparable 8-hour sessions of the 7-day pre-dose observation period.
3 secondary outcomes
Change in hourly histograms
Time frame: 8 hours
Detection reduction of >50%
Time frame: 9 days
Change in diary recorded seizures
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2024.
- Individual participant dataSharing planned: No. Detection rates before and after administration of intranasal diazepam will be made available.
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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.
Michael D Privitera principal investigator
University of Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing nasal diazepam in people with Epilepsies, Partial, run by University of Cincinnati at 1 site 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 12 inclusion and 16 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 12 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Detections (time frame: 8 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Apr 2024.