Trial reportJournal of neurodevelopmental disorders2025
A randomized, placebo-controlled, cross-over trial of ketamine in Rett syndrome.
Trial report in Journal of neurodevelopmental disorders, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03633058 (A Randomized, Double-blind, Placebo-controlled, Cross-over Study to Assess the Safety, Tolerability and Efficacy of Oral Ketamine for Patients With Rett Syndrome), which is not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double-blind, Placebo-controlled, Cross-over Study to Assess the Safety, Tolerability and Efficacy of Oral Ketamine for Patients With Rett Syndrome
Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A Systematic Review of Wearable Sensors in Rett Syndrome-What Physiological Markers Are Informative for Monitoring Disease States?Sensors (Basel, Switzerland) · 2025Pooled it
- Aperiodic and oscillatory activity of the human brain during induced emotional states.medRxiv : the preprint server for health sciences · 2026Article
- Ketamine alters the aperiodic EEG exponent in major depression: implications for cortical E/I balance and treatment prediction.Therapeutic advances in psychopharmacology · 2026Article
- Methodological challenges in outcomes research for early-trials for implementation of new therapies in neuropediatric rare diseases.Orphanet journal of rare diseases · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
backgroundPreclinical studies and anecdotal case reports support the potential therapeutic benefit of low-dose oral ketamine as a treatment of clinical symptoms in Rett syndrome (RTT); however, no controlled studies have been conducted in RTT to evaluate safety, tolerability and efficacy.
designThis was a sequentially initiated, dose-escalating cohort, placebo-controlled, double blind, randomized sequence, cross-over study of oral ketamine in 6-12-year-old girls with RTT to evaluate short-term safety and tolerability and explore efficacy.
methodsParticipants were randomized to either five days treatment with oral ketamine or matched placebo, followed by a nine-day wash-out period and then crossed-over to the opposite treatment. Ketamine was dosed twice daily at 0.75 mg/kg/dose (Cohort 1) or 1.5 mg/kg/dose (Cohort 2). An independent safety monitoring committee evaluated safety and approved proceeding to the next dose cohort. Caregivers, participants, outcome assessors, and study staff except pharmacists were blinded to allocation. The primary endpoint was safety and tolerability. Exploratory efficacy endpoints included change in clinician- and caregiver-rated measures of RTT features, brain activity on electroencephalography, and wearable biosensors to measure respiration, heart rate, sleep, and activity.
resultsTwenty-three participants enrolled (11 in Cohort 1, 12 in Cohort 2) from 3/12/2019-11/22/2021. One participant was excluded from analysis due to not meeting inclusion criteria on blinded review prior to analysis. One participant was withdrawn from the study due to an adverse event (vomiting) after the first dose of ketamine. Although planned for four dose cohorts, the trial was stopped after Cohort 2 due to enrollment challenges associated with the COVID-19 pandemic. Ketamine was safe and tolerated in both cohorts, with 1 related treatment emergent adverse event of vomiting. No difference was observed in efficacy between ketamine and placebo. Electroencephalography showed the expected increase in high frequency power with ketamine.
conclusionsShort-term, low-dose oral ketamine was safe and well tolerated in girls with RTT. No clinical efficacy of ketamine in treating symptoms of RTT was observed with 5 days of treatment, despite electroencephalography evidence of ketamine target engagement during the first dose. Further studies are needed to evaluate safety and efficacy of higher dose and longer exposure to ketamine in RTT.
trial registrationRegistered at clinicaltrials.gov NCT03633058.
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