Efficacy Study of Acetazolamide Versus Diazepam in Continuous Spike and Wave/Landau-Kleffner Syndrome
Primary Purpose
Landau-Kleffner Syndrome, Status Epilepticus, Electrographic
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Diazepam
Acetazolamide
Sponsored by
About this trial
This is an interventional treatment trial for Landau-Kleffner Syndrome focused on measuring continuous spike wave in sleep, Landau-Kleffner syndrome, acetazolamide, diazepam
Eligibility Criteria
Inclusion Criteria:
- 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%
Exclusion Criteria:
- 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
- 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
Sites / Locations
- Mayo Clinic
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Diazepam
Acetazolamide
Arm Description
Diazepam 0.5 mg/kg (up to maximum 20 mg) by mouth nightly. Duration of therapy is 4 weeks.
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.
Outcomes
Primary Outcome Measures
Short-term Tolerability of Acetazolamide vs Diazepam
Expect improved side effect profile of acetazolamide compared to diazepam at short-term follow up
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02904265
Brief Title
Efficacy Study of Acetazolamide Versus Diazepam in Continuous Spike and Wave/Landau-Kleffner Syndrome
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Terminated
Why Stopped
Lack of enrollment
Study Start Date
September 2016 (undefined)
Primary Completion Date
July 26, 2019 (Actual)
Study Completion Date
July 26, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Landau-Kleffner Syndrome, Status Epilepticus, Electrographic
Keywords
continuous spike wave in sleep, Landau-Kleffner syndrome, acetazolamide, diazepam
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Diazepam
Arm Type
Active Comparator
Arm Description
Diazepam 0.5 mg/kg (up to maximum 20 mg) by mouth nightly. Duration of therapy is 4 weeks.
Arm Title
Acetazolamide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Diazepam
Other Intervention Name(s)
Valium
Intervention Type
Drug
Intervention Name(s)
Acetazolamide
Other Intervention Name(s)
Diamox, Diamox Sequels
Primary Outcome Measure Information:
Title
Short-term Tolerability of Acetazolamide vs Diazepam
Description
Expect improved side effect profile of acetazolamide compared to diazepam at short-term follow up
Time Frame
4-8 weeks of start of medications
10. Eligibility
Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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%
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katherine C. Nickels, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
26230617
Citation
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.
Results Reference
background
PubMed Identifier
8579219
Citation
De 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.
Results Reference
background
PubMed Identifier
24393416
Citation
Francois 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.
Results Reference
background
PubMed Identifier
11934510
Citation
Katayama 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.
Results Reference
background
PubMed Identifier
23953953
Citation
Sanchez 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.
Results Reference
background
PubMed Identifier
16939861
Citation
Wirrell 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.
Results Reference
background
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
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Efficacy Study of Acetazolamide Versus Diazepam in Continuous Spike and Wave/Landau-Kleffner Syndrome
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