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

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02904265
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arms: 2
• Duration (Months): 34.8
• Patients Per Site Per Month: 0.1

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Landau-Kleffner Syndrome; Status Epilepticus, Electrographic	Drug: Diazepam; Drug: Acetazolamide	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Sep 1, 2016
• Actual Primary Completion Date: Jul 26, 2019
• Actual Study Completion Date: Jul 26, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Diazepam Diazepam 0.5 mg/kg (up to maximum 20 mg) by mouth nightly. Duration of therapy is 4 weeks.	Drug: Diazepam; Other Names: Valium
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.	Drug: Acetazolamide; Other Names: Diamox Diamox Sequels

Outcome Measures

Primary Outcome Measures

1. Short-term Tolerability of Acetazolamide vs Diazepam [4-8 weeks of start of medications]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Katherine C. Nickels, M.D., Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 13, 2017

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

• 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.
• 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.
• 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.

• Responsible Party: Katherine C. Nickels, MD, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02904265
• Other Study ID Numbers: 16-002442
• First Posted: Sep 16, 2016
• Last Update Posted: Jun 11, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Katherine C. Nickels, MD, Mayo Clinic: continuous spike wave in sleep; Landau-Kleffner syndrome; acetazolamide; diazepam
• Additional relevant MeSH terms: Status Epilepticus; Landau-Kleffner Syndrome; Syndrome; Acetazolamide; Diazepam

Study Results

Participant Flow

Recruitment Details	Study closed due to only 3 participants recruited
Pre-assignment Detail	Study closed due to only 3 participants recruited

Arm/Group Title	Diazepam	Acetazolamide
Arm/Group Description	Diazepam 0.5 mg/kg (up to maximum 20 mg) by mouth nightly. Duration of therapy is 4 weeks. Diazepam	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. Acetazolamide
Period Title: Overall Study
STARTED	1	2
COMPLETED	0	0
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Diazepam	Acetazolamide	Total
Arm/Group 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. Acetazolamide	Total of all reporting groups
Overall Participants	1	2	3
Age (Count of Participants)
<=18 years	1 100%	2 100%	3 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	1	2	1.5
Sex: Female, Male (Count of Participants)
Female	0 0%	1 50%	1 33.3%
Male	1 100%	1 50%	2 66.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	2 100%	2 66.7%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Study closed due to only 3 participants recruited

Arm/Group Title	Diazepam	Acetazolamide
Arm/Group Description	Diazepam 0.5 mg/kg (up to maximum 20 mg) by mouth nightly. Duration of therapy is 4 weeks. Diazepam	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. Acetazolamide
Measure Participants	1	2
Count of Participants [Participants]	1 100%	2 100%

Adverse Events

Time Frame	Adverse events will be assessed for the duration of the study for each subject, for approximately 6 months. All adverse events will be followed through to resolution or until the investigators attribute the adverse event to a cause other than the study drugs or assesses them as chronic or stable.
Adverse Event Reporting Description	Study was closed due to only 3 participants recruited
Arm/Group Title	Diazepam		Acetazolamide
Arm/Group Description	Diazepam 0.5 mg/kg (up to maximum 20 mg) by mouth nightly. Duration of therapy is 4 weeks. Diazepam		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. Acetazolamide
All Cause Mortality
	Diazepam		Acetazolamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)
Serious Adverse Events
	Diazepam		Acetazolamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Diazepam		Acetazolamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.