Trial reportNature communications2024
A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss.
Trial report in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Efficacy of methylprednisolone sodium succinate combined with acoustic resonance therapy on inflammatory response indicators and cerebral microcirculation in patients with sudden sensorineural hearing loss.European journal of medical research · 2025Trial
- Pharmacotherapeutic Interventions for Sensorineural Hearing Loss: A Scoping Review.Audiology research · 2026Review
- Anatomical Integrity of the Human Cochlea Estimated with Optical Coherence Tomography for Future Clinical Application.Journal of the Association for Research in Otolaryngology : JARO · 2026Article
- Design and Synthesis of New Quinoxaline Analogs to Regenerate Sensory Auditory Hair Cells.Cells · 2025Article
- Treating Hearing Loss: From Cochlear Implantation to Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Anatomical integrity of the human cochlea estimated with optical coherence tomography for future clinical application.bioRxiv : the preprint server for biology · 2025Article
- The Notch ligand Jagged1 plays a dual role in cochlear hair cell regeneration.Nature communications · 2025Article
- Hearing loss: a global view for gene therapy approaches and challenges.European journal of pediatrics · 2025Review
- Rational Design of Inner Ear Drug Delivery Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Hearing restoration through hair cell regeneration: A review of recent advancements and current limitations.Hearing research · 2025Review
- Multicargo Porous Cochlear Electrode Coating for Antifibrosis After Cochlear Implantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Advancing precision ear medicine: leveraging animal models for disease insights and therapeutic innovations.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Inner Ear Gene Therapy: An Overview from Bench to Bedside.Molecular diagnosis & therapy · 2025Review
- Gene Therapy: An Historical Overview for Familial Hearing Loss.International journal of molecular sciences · 2025Review
- PKM2 controls cochlear development through lactate-dependent transcriptional regulation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Differential expression and regulation of FASLG by miR-5195/miR-3941 in age-related hearing loss.PloS one · 2025Article
- Artificial intelligence powers regenerative medicine into predictive realm.Regenerative medicine · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 7 institutions in 5 countries.
Funding
Abstract
Inhibition of Notch signalling with a gamma-secretase inhibitor (GSI) induces mammalian hair cell regeneration and partial hearing restoration. In this proof-of-concept Phase I/IIa multiple-ascending dose open-label trial (ISRCTN59733689), adults with mild-moderate sensorineural hearing loss received 3 intratympanic injections of GSI LY3056480, in 1 ear over 2 weeks. Phase I primary outcome was safety and tolerability. Phase lla primary outcome was change from baseline to 12 weeks in average pure-tone air conduction threshold across 2,4,8 kHz. Secondary outcomes included this outcome at 6 weeks and change from baseline to 6 and 12 weeks in pure-tone thresholds at individual frequencies, speech reception thresholds (SRTs), Distortion Product Otoacoustic Emissions (DPOAE) amplitudes, Signal to Noise Ratios (SNRs) and distribution of categories normal, present-abnormal, absent and Hearing Handicap Inventory for Adults/Elderly (HHIA/E). In Phase I (N = 15, 1 site) there were no severe nor serious adverse events. In Phase IIa (N = 44, 3 sites) the average pure-tone threshold across 2,4,8 kHz did not change from baseline to 6 and 12 weeks (estimated change -0.87 dB; 95% CI -2.37 to 0.63; P = 0.252 and -0.46 dB; 95% CI -1.94 to 1.03; P = 0.545, respectively), nor did the means of secondary measures. DPOAE amplitudes, SNRs and distribution of categories did not change from baseline to 6 and 12 weeks, nor did SRTs and HHIA/E scores. Intratympanic delivery of LY3056480 is safe and well-tolerated; the trial's primary endpoint was not met.
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What Socratic 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 Socratic graph.