Efficacy and Safety of Daily Home-based Hyperthermic Baths for Reducing Epileptic Seizures in CDKL5 Deficiency Disorder: A PROBE Clinical Trial

Efficacy and Safety of Daily Home-based Hyperthermic Baths for Reducing Epileptic Seizures in CDKL5 Deficiency Disorder: A Prospective, Randomized, Parallel-Controlled, Open-Label, Blinded Endpoint (PROBE) Clinical Trial

The primary objective of this research is to study the efficacy and safety of daily, home-based hyperthermic baths for reducing epileptic seizures in CDKL5 Deficiency Disorder.

This is a prospective, randomized, open-label, blinded-endpoint study designed to evaluate the efficacy and safety of daily home-based hyperthermic bathing in participants with CDKL5 deficiency disorder. Eligible participants will be randomized in a 1:1 ratio to receive either hyperthermic baths in addition to usual antiseizure care or usual antiseizure care alone without hyperthermic baths. Efficacy will be assessed primarily by changes in epileptic seizure burden, and safety will be evaluated throughout the study period.

Inclusion Criteria:

1. A diagnosis of CDKL5 deficiency disorder, including molecular confirmation of a pathogenic CDKL5 variant and exhibiting epileptic seizures.

2. Male or female participants aged 6 months to 14 years, inclusive.

3. Patients presenting with drug-resistant epilepsy that seizures were uncontrolled despite the appropriate trial of at least two antiseizure medications (ASMs).

4. At least 8 motor seizures during each 4 weeks in the 8-week historical seizure records preceding screening.

5. Treatment regimens of 0-4 ASMs were required to be stable for at least 4 weeks before screening and throughout the intervention. Ongoing ketogenic diets were allowed if remain unchanged during screening and treatment.

6. Subjects who have undergone surgical implantation of vagus nerve stimulation (VNS) will be eligible for inclusion in the study, provided they meet all of the following criteria:

   1. The VNS device has been in place for at least one year prior to the screening visit;
   2. The stimulation parameters remain unchanged throughout the duration of the trial.

7. Parents or caregivers must be able and willing to maintain an accurate and comprehensive daily electronic seizure diary throughout the duration of the study.

8. Participants' legal guardians willing to provide written informed consent.

Exclusion Criteria:

1. Patients who had any history of previous brain disease (including trauma, encephalitis, etc.) that were likely to precipitate seizures; defined by MRI outcomes.
2. Participants with skin ulceration or dermatologic conditions that make bathing unsuitable.
3. Parents or guardians who, based on past experiences, determine that the child has an intolerance to thermal baths.
4. A history of seizures induced by thermal baths, or an increase in seizure frequency after thermal baths.
5. Patients who presented any clinical condition that in the opinion of the principal investigator made the patient not suitable to participate in the survey.