Trial reportHuman molecular genetics2022
A randomized controlled trial of everolimus for neurocognitive symptoms in PTEN hamartoma tumor syndrome.
Trial report in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02991807 (A Randomized Double-Blind Controlled Trial of Everolimus in Individuals With PTEN Mutations), which is not on this map. Cited by 21 papers.
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 Controlled Trial of Everolimus in Individuals With PTEN Mutations (RAD001XUS257T)
Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Sensitivity Analysis of the Efficacy of Everolimus for Neurocognitive Symptoms in PTEN Hamartoma Tumor Syndrome.Advances in therapy · 2026Trial
- AAV9-MediatedPharmaceutics · 2026Article
- Acute rapamycin treatment reveals distinct mechanisms of dysfunction in a maternal inflammation mouse model.Nature communications · 2026Article
- Scaling of Neuronal Growth and Excitability Through Separable mTORC1 and mTORC2 Pathways.bioRxiv : the preprint server for biology · 2026Article
- Repurposing drugs for treating the neurobehavioral manifestations of PTEN hamartoma tumor syndrome.iScience · 2026Article
- ARP2/3 complex mediates the neuropathology of PTEN-deficient human neural cells downstream of mTORC1 and mTORC2 hyperactivation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Neuronal hyperactivity becomes mTORC1 independent due to transcriptional changes in tuberous sclerosis complex disease models.Cell reports · 2025Article
- Precision diagnostic and therapeutic interventions in rare genetic neurodevelopmental disorders.Pediatric research · 2025Review
- Proposed Mechanistic Axis of Infections and mTOR Hyperactivation: A Multidisciplinary Review of Immune, Rheumatologic, and Psychiatric Links.Children (Basel, Switzerland) · 2025Review
- Targeted therapy in patients with genetic tumor syndromes.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- PTEN deficiency in postnatally developing Purkinje cells disrupts metabolic signaling, leading to dendritic abnormalities and sex-specific behavioral deficits.Scientific reports · 2025Article
- mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node.Orphanet journal of rare diseases · 2025Review
- Remote monitoring of social attention in neurogenetic syndromes and idiopathic neurodevelopmental disability.Autism research : official journal of the International Society for Autism Research · 2025Article
- mTORC1-selective inhibitors rescue cellular phenotypes in TSC iPSC-derived neurons.Frontiers in neuroscience · 2025Article
- Reverse repurposing: Potential utility of cancer drugs in nonmalignant illnesses.Med (New York, N.Y.) · 2024Review
- An integrated clinical approach to children at genetic risk for neurodevelopmental and psychiatric conditions: interdisciplinary collaboration and research infrastructure.Journal of neurodevelopmental disorders · 2024Article
- Exploring the neurological features of individuals with germline PTEN variants: A multicenter study.Annals of clinical and translational neurology · 2024Article
- Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic.Frontiers in psychiatry · 2024Review
- Development of webcam-collected and artificial-intelligence-derived social and cognitive performance measures for neurodevelopmental genetic syndromes.American journal of medical genetics. Part C, Seminars in medical genetics · 2023Article
- mTOR Signaling Disruption and Its Association with the Development of Autism Spectrum Disorder.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
PTEN hamartoma tumor syndrome (PHTS) is a complex neurodevelopmental disorder characterized by mechanistic target of rapamycin (mTOR) overactivity. Limited data suggest that mTOR inhibitors may be therapeutic. No placebo-controlled studies have examined mTOR inhibition on cognition and behavior in humans with PHTS with/without autism. We conducted a 6-month phase II, randomized, double-blinded, placebo-controlled trial to examine the safety profile and efficacy of everolimus (4.5 mg/m2) in individuals (5-45 years) with PHTS. We measured several cognitive and behavioral outcomes, and electroencephalography (EEG) biomarkers. The primary endpoint was a neurocognitive composite derived from Stanford Binet-5 (SB-5) nonverbal working memory score, SB-5 verbal working memory, Conners' Continuous Performance Test hit reaction time and Purdue Pegboard Test score. Forty-six participants underwent 1:1 randomization: n = 24 (everolimus) and n = 22 (placebo). Gastrointestinal adverse events were more common in the everolimus group (P < 0.001). Changes in the primary endpoint between groups from baseline to Month 6 were not apparent (Cohen's d = -0.10, P = 0.518). However, several measures were associated with modest effect sizes (≥0.2) in the direction of improvement, including measures of nonverbal IQ, verbal learning, autism symptoms, motor skills, adaptive behavior and global improvement. There was a significant difference in EEG central alpha power (P = 0.049) and central beta power (P = 0.039) 6 months after everolimus treatment. Everolimus is well tolerated in PHTS; adverse events were similar to previous reports. The primary efficacy endpoint did not reveal improvement. Several secondary efficacy endpoints moved in the direction of improvement. EEG measurements indicate target engagement following 6 months of daily oral everolimus. Trial Registration Information: ClinicalTrials.gov NCT02991807 Classification of Evidence: I.
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What OpenQuestion holds
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.