Melatonin for the Treatment of DEE-SWAS

Melatonin for the Treatment of Developmental/Epileptic Encephalopathy With Spike Wave Activation In Sleep (DEE-SWAS; Formerly ESES)

The goal of this study is to learn if melatonin, a naturally produced substance, can help to treat some of the symptoms of DEE-SWAS, a type of epilepsy that causes children to lose skills and development. It will look at doses of melatonin that are higher than most people use.

The study will look at the safety of melatonin in patients with DEE-SWAS The study will look at the ways melatonin affects abnormal brain activity on a study called an EEG.

The study will look at the ways melatonin affects normal brain activity that occurs in sleep.

Study Overview

• Status: Not yet recruiting
• Conditions: Electrical Status Epilepticus in Sleep; CSWS; Developmental and/or Epileptic Encephalopathies
• Intervention / Treatment: Drug: Melatonin

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Clinic Dx of DEE-SWAS

1. Dx of DEE-SWAS by a board-certified pediatric neurology/epileptologist Clinical history of delayed milestones in at least 1 category, regression of milestones in at least 1 category, and/or failure to progress in milestones in at least 1 category
2. Abnormal baseline neuropsychiatric testing consistent with Dx Abnormal EEG
3. Epileptiform abnormalities (spike, polyspike, sharp) in at least 1 head region
4. Increase by 2-fold of epileptiform abnormalities during NREM sleep as compared to wakefulness
5. SWI of ≥50% in at least one head region on overnight EEG

Exclusion Criteria:

1. Allergic to ingredients in study drug Melatonin

   • Hypoallergenic plant fiber (cellulose)
   • Active use of the medication viloxazine
2. History of known cardiac rhythm abnormalities, heart failure or decreased EF <30%
3. History of known pulm requiring oxygen or invasive positive pressure ventilation. Patients with non-invasive PPV (e.g. CPAP) due OSA w/o 02 requirement, rate, or DX of CSA, on stable pressure settings for >3 mnths will not be excluded.
4. History of liver dysf OR AST/ALT/AlkPhos >2.5 ULN w/i year. If lab value meeting exclusion between 3-12 months, a repeat lab value < 2.5 ULN will be considered for inclusion
5. Post-menarchal participants. of childbearing potential with a positive urine pregnancy test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melatonin; Melatonin 0.3mg/kg (20mg max)	Drug: Melatonin; Melatonin will be used in single fixed dose as described

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	This study will evaluate for adverse events associated with single high dose melatonin administration	Within 24 hours of dose administration
Side effects	This study will evaluate for multiorgan adverse effects associated with single high dose melatonin administration based on standardized questionnaire assessment. The assessment is a multiorgan adverse event questionnaire described in Jarernsiripornkul 2001, modified to reflect single dosing rather than chronic dosing. The results of this questionanaire are descriptive.	Within 24 hours of dose administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spike wave index (SWI)	This study will evaluate change in epileptiform activity during NREM sleep as defined by common clinical definition of SWI - average percentage of second bins containing an epileptiform discharge during NREM sleep	Within 24 hours of dose administration
Sleep spindle	This study will evaluate change in sleep spindle activity during NREM sleep using both blinded review and validated deep learning algorithmic detection.	Within 24 hours of dose administration
Salivary melatonin pharmacokinetics	Baseline and post intervention salivary melatonin levels will be obtained at multiple time points	24 hours prior to intervention and 24 hours following intervention

Collaborators and Investigators

• Sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
• Collaborators: Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: October 27, 2025
• First Submitted That Met QC Criteria: October 27, 2025
• First Posted (Estimated): October 29, 2025

Study Record Updates

• Last Update Posted (Estimated): October 30, 2025
• Last Update Submitted That Met QC Criteria: October 28, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: melatonin; CSWS; ESES; epileptic encephalopathy; DEE-SWAS
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indoles; Tryptamines; Melatonin
• Other Study ID Numbers: IRB00478764

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes