Trial reportNature medicine2023
Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study.
Trial report in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04181723 (A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome), which is not on this map. Cited by 111 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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, Parallel-Group Study of Trofinetide for the Treatment of Girls and Women With Rett Syndrome
Who cites it
111 citing papers in PubMed, 6 syntheses or guidelines pooled it, 178 citations in OpenAlex.
- A Systematic Review of Wearable Sensors in Rett Syndrome-What Physiological Markers Are Informative for Monitoring Disease States?Sensors (Basel, Switzerland) · 2025Pooled it
- Mecasermin for the treatment of Rett Syndrome: a systematic review.Neurogenetics · 2025Pooled it
- A meta-analysis of the efficacy and safety of trofinetide in patients with rett syndrome.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Pooled it
- Is trofinetide a future treatment for Rett syndrome? A comprehensive systematic review and meta-analysis of randomized controlled trials.BMC medicine · 2024Pooled it
- Safety and efficacy of trofinetide in Rett syndrome: a systematic review and meta-analysis of randomized controlled trials.BMC pediatrics · 2024Pooled it
- Parent-reported outcome measures evaluating communication in individuals with rare neurodevelopmental disorders: A systematic review.International journal of language & communication disordersPooled it
- A Phase 1, Randomized, Open-Label Study to Assess the Bioequivalence of Trofinetide as a Ready-to-Use Oral Solution and Constituted Powder for Oral Solution in Healthy Adults.Advances in therapy · 2026Trial
- Managing Gastrointestinal Symptoms Resulting from Treatment with Trofinetide for Rett Syndrome: Caregiver and Nurse Perspectives.Advances in therapy · 2024Trial
- Exposure-Response Efficacy Modeling to Support Trofinetide Dosing in Individuals with Rett Syndrome.Advances in therapy · 2024Trial
- Real-World Demographics, Clinical Characteristics, and Predictors of Persistence Among Males with Rett Syndrome Treated with Trofinetide.Advances in therapy · 2026Article
- Understanding Caregivers' Experiences of Rett Syndrome: A Multinational Study of Symptoms and Meaningful Outcomes of Potential Treatments.Neurology and therapy · 2026Article
- Fenfluramine in Rett syndrome: A multidimensional clinical study.Epilepsia open · 2026Article
- Rett syndrome: MECP2 biology, multisystem pathophysiology, and the evolving therapeutic landscape.European journal of pediatrics · 2026Review
- Mapping Trofinetide Polypharmacology in Rett Syndrome: A Multi-Stage Computational Analysis.Journal of computational chemistry · 2026Article
- Utilization of Non-pharmacological Interventions in Rett Syndrome: A Systematic Review of the Literature on Supportive Care Management.Neurology and therapy · 2026Review
- MECP2Science China. Life sciences · 2026Article
- Inhibition of protein tyrosine phosphatase PTP1B function ameliorates pathophysiological deficits in Rett Syndrome.bioRxiv : the preprint server for biology · 2026Article
- Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways.Metabolic brain disease · 2026Review
- Gait Analysis in Rett Syndrome: Integrating Linear and Nonlinear Techniques.Journal of child neurology · 2026Article
- Content Validation of the Communication Inventory Disability-Observer Reported (CID-OR).Journal of child neurology · 2026Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 7 institutions in 1 country.
Funding
Abstract
Rett syndrome is a rare, genetic neurodevelopmental disorder. Trofinetide is a synthetic analog of glycine-proline-glutamate, the N-terminal tripeptide of the insulin-like growth factor 1 protein, and has demonstrated clinical benefit in phase 2 studies in Rett syndrome. In this phase 3 study ( https://clinicaltrials.gov identifier NCT04181723 ), females with Rett syndrome received twice-daily oral trofinetide (n = 93) or placebo (n = 94) for 12 weeks. For the coprimary efficacy endpoints, least squares mean (LSM) change from baseline to week 12 in the Rett Syndrome Behaviour Questionnaire for trofinetide versus placebo was -4.9 versus -1.7 (P = 0.0175; Cohen's d effect size, 0.37), and LSM Clinical Global Impression-Improvement at week 12 was 3.5 versus 3.8 (P = 0.0030; effect size, 0.47). For the key secondary efficacy endpoint, LSM change from baseline to week 12 in the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist Social Composite score was -0.1 versus -1.1 (P = 0.0064; effect size, 0.43). Common treatment-emergent adverse events included diarrhea (80.6% for trofinetide versus 19.1% for placebo), which was mostly mild to moderate in severity. Significant improvement for trofinetide compared with placebo was observed for the coprimary efficacy endpoints, suggesting that trofinetide provides benefit in treating the core symptoms of Rett syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.