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

NCT02904265 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 16-002442
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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).

Conditions

Landau-Kleffner Syndrome; Status Epilepticus, Electrographic

Keywords

continuous spike wave in sleep; Landau-Kleffner syndrome; acetazolamide; diazepam

Outcome Measures

Primary Outcomes (1)

• Short-term Tolerability of Acetazolamide vs Diazepam

  Expect improved side effect profile of acetazolamide compared to diazepam at short-term follow up

  4-8 weeks of start of medications

Study Arms (2)

Diazepam

ACTIVE COMPARATOR

Diazepam 0.5 mg/kg (up to maximum 20 mg) by mouth nightly. Duration of therapy is 4 weeks.

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.

Drug: Acetazolamide

Interventions

Diazepam DRUG

Also known as: Valium

Diazepam

Acetazolamide DRUG

Also known as: Diamox, Diamox Sequels

Acetazolamide

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (6)

• 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.

  PMID: 26230617 BACKGROUND

• 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.

  PMID: 8579219 BACKGROUND

• 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.

  PMID: 24393416 BACKGROUND

• 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.

  PMID: 11934510 BACKGROUND

• 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.

  PMID: 23953953 BACKGROUND

• 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.

  PMID: 16939861 BACKGROUND

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Landau-Kleffner Syndrome; Status Epilepticus

Interventions

Diazepam; Acetazolamide

Condition Hierarchy (Ancestors)

Epileptic Syndromes; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Seizures; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. Katherine Nickels
• Organization: Mayo Clinic

nickels.katherine@mayo.edu

5072660774

Study Officials

• Katherine C. Nickels, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: September 16, 2016
• Study Start: September 1, 2016
• Primary Completion: July 26, 2019
• Study Completion: July 26, 2019
• Last Updated: June 11, 2020
• Results First Posted: June 11, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)