Efficacy Study of Acetazolamide Versus Diazepam in Continuous Spike and Wave/Landau-Kleffner Syndrome

Overview

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).

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 26, 2019

Interventions

  • Drug: Diazepam
  • Drug: Acetazolamide

Arms, Groups and Cohorts

  • Active Comparator: Diazepam
    • Diazepam 0.5 mg/kg (up to maximum 20 mg) by mouth nightly. Duration of therapy is 4 weeks.
  • Experimental: Acetazolamide
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 3 Years

Maximum Age: 12 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mayo Clinic
  • Provider of Information About this Clinical Study
    • Principal Investigator: Katherine C. Nickels, MD – Mayo Clinic
  • Overall Official(s)
    • Katherine C. Nickels, M.D., Principal Investigator, Mayo Clinic

References

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.

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.

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.

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.

Sánchez Fernández 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.

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.

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