Landau-Kleffner SyndromePhase 2/3NCT02904265
Efficacy Study of Acetazolamide Versus Diazepam in Continuous Spike and Wave/Landau-Kleffner Syndrome
A Phase 2/3 study testing Diazepam and Acetazolamide in people with Landau-Kleffner Syndrome and Status Epilepticus, Electrographic, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is to compare the effectiveness of the medications acetazolamide and diazepam in the treatment of continuous spike wave in sleep (CSWS) and Landau-Kleffner syndrome (LKS). Read more about this study
- Who is it for?
- Ages 3 to 12 years
- Conditions the study is for
- Landau-Kleffner Syndrome, Status Epilepticus, Electrographic
- What is being tested?
- Diazepam and Acetazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to 26 Jul 2019
- Phase
- Phase 2/3
- 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 3 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- ESES and clinical CSWS/LKS defined by all of the following:
- SWI ≥50% during first hour of sleep
- Bilateral synchrony of discharges during sleep
- Clinical evidence of behavior and/or academic regression
- Daytime SWI ≤20%
Who cannot join
- Previous treatment with benzodiazepine or acetazolamide for Electrical Status Epilepticus in Sleep (ESES)
- Current treatment with carbamazepine, phenytoin, oxcarbazepine, phenobarbital, vigabatrin or lamotrigine
- Antiepileptic medication changes over the month prior to enrollment
- Epileptic encephalopathy other than CSWS/LKS
- Prior serious adverse reaction to benzodiazepines or acetazolamide
- Sulfa allergy
Show all 9Show fewer
- Progressive underlying neurologic condition
- Frequent seizures that would prevent the patient from maintaining a stable dose of medications
- Female patient that has begun menses or is pregnant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Non-inferiority Prospective Randomized Trial of Acetazolamide Versus Diazepam in Patients With Continuous Spike and Wave in Sleep (CSWS)/Landau Kleffner Syndrome (LKS)
The purpose of this study is to compare the effectiveness of the medications acetazolamide and diazepam in the treatment of continuous spike wave in sleep (CSWS) and Landau-Kleffner syndrome (LKS).
- Being tested
- Diazepam, Acetazolamide
- Keywords
- continuous spike wave in sleep, Landau-Kleffner syndrome, acetazolamide, diazepam
- Medical subject headings
- Landau-Kleffner Syndrome, Status Epilepticus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DiazepamDrug
Also called Valium
AcetazolamideDrug
Also called Diamox, Diamox Sequels
| Study group | Role | What they receive |
|---|---|---|
| Diazepam | Active comparator | Diazepam 0.5 mg/kg (up to maximum 20 mg) by mouth nightly. Duration of therapy is 4 weeks. Receives: Drug: Diazepam |
| Acetazolamide | Experimental | Acetazolamide 8-10 mg/kg (up to a maximum dose of 375 mg) by mouth (PO)divided twice daily X 1 week, then increased to 11-16 mg/kg (up to a maximum dose of 750 mg) by mouth divided twice daily thereafter. Duration of therapy is 4-8 weeks. Receives: Drug: Acetazolamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Short-term Tolerability of Acetazolamide vs Diazepam
Expect improved side effect profile of acetazolamide compared to diazepam at short-term follow up
Measured: 4-8 weeks of start of medications
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2016 (estimated)
- Study startSep 2016
- Primary completion26 Jul 2019
- Study completion26 Jul 2019
Why it stopped: Lack of enrollment
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.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Landau-Kleffner SyndromeStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Katherine C. Nickels, Mayo Clinic
- Investigators
- Katherine C. Nickels, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02904265
- Sponsor's protocol ID
- 16-002442
- Status last verified
- May 2020
- First submitted
- 13 Sep 2016
- Last updated
- 11 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fine AL, Wirrell EC, Wong-Kisiel LC, Nickels KC. Acetazolamide for electrical status epilepticus in slow-wave sleep. Epilepsia. 2015 Sep;56(9):e134-8. doi: 10.1111/epi.13101. Epub 2015 Jul 31.
PubMed 26230617De Negri M, Baglietto MG, Battaglia FM, Gaggero R, Pessagno A, Recanati L. Treatment of electrical status epilepticus by short diazepam (DZP) cycles after DZP rectal bolus test. Brain Dev. 1995 Sep-Oct;17(5):330-3. doi: 10.1016/0387-7604(95)00076-n.
PubMed 8579219Francois D, Roberts J, Hess S, Probst L, Eksioglu Y. Medical management with diazepam for electrical status epilepticus during slow wave sleep in children. Pediatr Neurol. 2014 Mar;50(3):238-42. doi: 10.1016/j.pediatrneurol.2013.11.002. Epub 2013 Nov 12.
PubMed 24393416Katayama F, Miura H, Takanashi S. Long-term effectiveness and side effects of acetazolamide as an adjunct to other anticonvulsants in the treatment of refractory epilepsies. Brain Dev. 2002 Apr;24(3):150-4. doi: 10.1016/s0387-7604(02)00003-7.
PubMed 11934510Sanchez Fernandez I, Peters JM, An S, Bergin AM, Takeoka M, Rotenberg A, Kothare SV, Riviello JJ Jr, Loddenkemper T. Long-term response to high-dose diazepam treatment in continuous spikes and waves during sleep. Pediatr Neurol. 2013 Sep;49(3):163-170.e4. doi: 10.1016/j.pediatrneurol.2013.04.027.
PubMed 23953953Wirrell E, Ho AW, Hamiwka L. Sulthiame therapy for continuous spike and wave in slow-wave sleep. Pediatr Neurol. 2006 Sep;35(3):204-8. doi: 10.1016/j.pediatrneurol.2006.02.012.
PubMed 16939861
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-inferiority Prospective Randomized Trial of Acetazolamide Versus Diazepam in Patients With Continuous Spike and Wave in Sleep (CSWS)/Landau Kleffner Syndrome (LKS)
- ClinicalTrials.gov ID
- NCT02904265
- Acronym / sponsor ID
- 16-002442
- Keywords
- continuous spike wave in sleep, Landau-Kleffner syndrome, acetazolamide, diazepam
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- Sep 2016
- Primary completion
- 26 Jul 2019 (actual)
- Study completion
- 26 Jul 2019 (actual)
- First posted
- 16 Sep 2016 (estimated)
- Results
- Posted 11 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the effectiveness of the medications acetazolamide and diazepam in the treatment of continuous spike wave in sleep (CSWS) and Landau-Kleffner syndrome (LKS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diazepam | Active comparator | Drug: DiazepamDiazepam 0.5 mg/kg (up to maximum 20 mg) by mouth nightly. Duration of therapy is 4 weeks. |
| Acetazolamide | Experimental | Drug: AcetazolamideAcetazolamide 8-10 mg/kg (up to a maximum dose of 375 mg) by mouth (PO)divided twice daily X 1 week, then increased to 11-16 mg/kg (up to a maximum dose of 750 mg) by mouth divided twice daily thereafter. Duration of therapy is 4-8 weeks. |
Who may qualify
- Ages
- 3 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- ESES and clinical CSWS/LKS defined by all of the following:
- SWI ≥50% during first hour of sleep
- Bilateral synchrony of discharges during sleep
- Clinical evidence of behavior and/or academic regression
- Daytime SWI ≤20%
Key exclusion criteria (9 listed)
- Previous treatment with benzodiazepine or acetazolamide for Electrical Status Epilepticus in Sleep (ESES)
- Current treatment with carbamazepine, phenytoin, oxcarbazepine, phenobarbital, vigabatrin or lamotrigine
- Antiepileptic medication changes over the month prior to enrollment
- Epileptic encephalopathy other than CSWS/LKS
- Prior serious adverse reaction to benzodiazepines or acetazolamide
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 |
|---|---|---|
| DiazepamAlso: Valium | Drug | Diazepam |
| AcetazolamideAlso: Diamox, Diamox Sequels | Drug | Acetazolamide |
Primary outcome
Short-term Tolerability of Acetazolamide vs Diazepam
Time frame: 4-8 weeks of start of medications
Expect improved side effect profile of acetazolamide compared to diazepam at short-term follow up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26230617Fine AL, Wirrell EC, Wong-Kisiel LC, Nickels KC. Acetazolamide for electrical status epilepticus in slow-wave sleep. Epilepsia. 2015 Sep;56(9):e134-8. doi: 10.1111/epi.13101. Epub 2015 Jul 31.
- Background: PubMed 8579219De Negri M, Baglietto MG, Battaglia FM, Gaggero R, Pessagno A, Recanati L. Treatment of electrical status epilepticus by short diazepam (DZP) cycles after DZP rectal bolus test. Brain Dev. 1995 Sep-Oct;17(5):330-3. doi: 10.1016/0387-7604(95)00076-n.
- Background: PubMed 24393416Francois D, Roberts J, Hess S, Probst L, Eksioglu Y. Medical management with diazepam for electrical status epilepticus during slow wave sleep in children. Pediatr Neurol. 2014 Mar;50(3):238-42. doi: 10.1016/j.pediatrneurol.2013.11.002. Epub 2013 Nov 12.
- Background: PubMed 11934510Katayama F, Miura H, Takanashi S. Long-term effectiveness and side effects of acetazolamide as an adjunct to other anticonvulsants in the treatment of refractory epilepsies. Brain Dev. 2002 Apr;24(3):150-4. doi: 10.1016/s0387-7604(02)00003-7.
- Background: PubMed 23953953Sanchez Fernandez I, Peters JM, An S, Bergin AM, Takeoka M, Rotenberg A, Kothare SV, Riviello JJ Jr, Loddenkemper T. Long-term response to high-dose diazepam treatment in continuous spikes and waves during sleep. Pediatr Neurol. 2013 Sep;49(3):163-170.e4. doi: 10.1016/j.pediatrneurol.2013.04.027.
- Background: PubMed 16939861Wirrell E, Ho AW, Hamiwka L. Sulthiame therapy for continuous spike and wave in slow-wave sleep. Pediatr Neurol. 2006 Sep;35(3):204-8. doi: 10.1016/j.pediatrneurol.2006.02.012.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- 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.
Katherine C. Nickels, M.D. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Diazepam and Acetazolamide in people with Landau-Kleffner Syndrome and Status Epilepticus, Electrographic, run by Mayo Clinic 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 5 inclusion and 9 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: stopped early, as of the sponsor's last update on 11 Jun 2020. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 11 Jun 2020). 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?
Short-term Tolerability of Acetazolamide vs Diazepam (time frame: 4-8 weeks of start of medications). 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 NCT02904265, which also lists 6 linked publications.
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 11 Jun 2020.