Esketamine for the Treatment of Rett Syndrome

An Exploratory Trial of Esketamine for the Treatment of Rett Syndrome

The goal of this interventional study is to learn about the efficacy and safety of Esketamine for treating children with Rett syndrome (RTT).

The main questions it aims to answer are:

• whether Esketamine treatment is effective in improving symptom severity for RTT.
• whether Esketamine is safe in the treatment of RTT. Participants will receive a weekly intravenous infusion of Esketamine for five weeks and will be assessed for disease severity and drug safety.

Study Overview

• Status: Completed
• Conditions: Rett Syndrome
• Intervention / Treatment: Drug: Esketamine hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361006
      • Xiamen Children's Hospital (Children's Hospital of Fudan University at Xiamen)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Classic/typical RTT
• Causing mutation in MECP2 gene
• Stable pattern of seizures, or has had no seizures at least 8 weeks

Exclusion Criteria:

• Use of other drugs that interact with Esketamine: thyroxine, meglumine diatrizoate, aminophylline, diazepam or midazolam, drugs for antihypertension or central nervous depressants, halogenated general anesthetics (e.g., halothane), tubocurarine, atracurium
• Condition with hypertension, high cerebrospinal fluid pressure, and high intraocular pressure
• Unstable systemic illness other than Rett syndrome: current clinically significant cardiovascular, endocrine (such as hypo- or hyperthyroidism, type 1 diabetes, or uncontrolled type 2 diabetes), renal, hepatic, respiratory, or gastrointestinal disease (such as celiac disease or inflammatory bowel disease), or major surgery planned during the study
• Clinically important variations in medication use

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: Esketamine treatment; Esketamine, diluted with 20ml Saline at a dose of 0.25mg/kg, intravenously for 40 minutes, once a week; 5 weeks in total.	Drug: Esketamine hydrochloride; Intravenous infusion of Ketamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse events	Safety of treatment with Esketamine in girls with RTT	baseline, week 5
Efficacy of treatment with Esketamine in girls with RTT	Rett Syndrome Behaviour Questionnaire (RSBQ) total score; Minimum value 0; Maximum values 90; higher scores mean a worse outcome.	baseline, week 5, and month 6
Co-outcome for efficacy of treatment with Esketamine in girls with RTT	Clinical Global Impressions Scale-improvement (CGI-I) score; Minimum value 0; Maximum values 7; higher scores mean a worse outcome.	baseline, week 5, and month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Revised-Motor Behavior Assessment scale (R-MBA)	Subscale score, 0-100, higher sores means a worse outcome	baseline, week 5, and month 6
Rett Syndrome Severity Scale (RSSS)	Subscale score, 0-21, higher sores means a worse outcome	baseline, week 5, and month 6
Sleep improvement by Esketamine treatment	Sleep record	baseline, week 5, and month 6
Behavior observation	Unusual hand movements duration per hour	baseline, week 5, and month 6
Autism Diagnostic Observation Schedule, Second Edition (ADOS-2)	Total score，; Minimum value 0; Maximum values 28; higher scores mean a worse outcome.	baseline, week 5, and month 6
Griffiths Scales of Child Development	Development quotient; Minimum value 0; Maximum values 96; higher scores mean a better outcome.	baseline, week 5, and month 6
Brain image change	Magnetic Resonance Imaging (MRI)；brain network connectivity	baseline, week 5, and month 6
Brain function change	Electroencephalogram (EEG); brain-wave activity	baseline, week 5, and month 6

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Investigators: Principal Investigator: Huiping Li, Children's Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2023
• Primary Completion (Actual): December 30, 2025
• Study Completion (Actual): December 30, 2025

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: December 28, 2023
• First Posted (Actual): January 10, 2024

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: safety; efficacy; Rett syndrome; Esketamine
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, Inborn; Neurobehavioral Manifestations; Heredodegenerative Disorders, Nervous System; Intellectual Disability; Genetic Diseases, X-Linked; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; X-Linked Intellectual Disability; Rett Syndrome; Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: EskRTT2023; XE2023-ETBJ-D01 (Other Grant/Funding Number: Fujian Province Clinical Key Specialty Construction Project)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all collected IPD, all IPD that underlie results in a publication
• IPD Sharing Time Frame: starting 6 months after publication，for one year
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No