Trial reportJCI insight2021
A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome.
Trial report in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02829268 (A Phase 1b/2a Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome), which is not on this map. Cited by 37 papers, 1 of them a synthesis 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 Phase 1b/2a Trial of Dantrolene Sodium in Pediatric and Adult Patients With Wolfram Syndrome
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Wolfram Syndrome Type 2: A Systematic Review of a Not Easily Identifiable Clinical Spectrum.International journal of environmental research and public health · 2022Pooled it
- Consensus Recommendations for the Clinical Management of Wolfram syndrome Using a Delphi Method.medRxiv : the preprint server for health sciences · 2026Article
- Breaking the Calcium Overload Cycle in Acute Pancreatitis: Emerging Pharmacological Strategies.Digestive diseases and sciences · 2026Review
- Expanding the phenotype of Wolfram syndrome: adult presentation with a novelJCEM case reports · 2026Article
- Genotype-Based Severity Scoring System in Wolfram Syndrome: Correlation with Onset of Cardinal Symptoms andmedRxiv : the preprint server for health sciences · 2026Article
- Mitochondrial dysfunction in neurodegenerative disorders: mechanisms and therapeutic advances.Molecular biomedicine · 2026Review
- Mitochondrial dysfunction in type 1 diabetes and its implications for pancreatic beta-cell survival and insulin secretion.Acta diabetologica · 2026Review
- Selected Brain Metabolites and Mitochondrial DNA Copy Number as Potential Markers of Ongoing Neurodegeneration in Patients with Wolfram Syndrome.Metabolites · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Genotype-based severity scoring system in Wolfram Syndrome: correlation with onset of cardinal symptoms andFrontiers in genetics · 2026Article
- Evaluating the use of GLP-1 receptor agonists in Wolfram syndrome patients.Frontiers in endocrinology · 2026Article
- Could R-Ketamine and Wolfram Syndrome Inform Understanding of Depression and Suicidality? A Sigma-1 Receptor-Based Perspective.Human psychopharmacology · 2025Review
- Reciprocal rescue of Wolfram syndrome by two causative genes.EMBO reports · 2025Article
- GABA and GLP-1 receptor agonist combination therapy modifies diabetes and Langerhans islet cytoarchitecture in a rat model of Wolfram syndrome.Diabetology & metabolic syndrome · 2025Article
- Clinical trials for Wolfram syndrome neurodegeneration: Novel design, endpoints, and analysis models.PloS one · 2025Article
- Clinical Research for Inherited Retinal Disease Related Pediatric Blindness: A Preliminary Descriptive Analysis Based on ClinicalTrials.gov.Journal of multidisciplinary healthcare · 2025Article
- Diabetes mellitus and pregnancy in Wolfram syndrome type 1: a case report with review of clinical and pathophysiological aspects.Frontiers in medicine · 2025Article
- ER calcium depletion as a key driver for impaired ER-to-mitochondria calcium transfer and mitochondrial dysfunction in Wolfram syndrome.Nature communications · 2024Article
- Cardiac Wolframinopathies: A Case Report of Myocarditis and a Literature Review of Cardiac Involvement in Wolfram Syndrome 1.Journal of clinical medicine · 2024Review
- Comprehensive overview of disease models for Wolfram syndrome: toward effective treatments.Mammalian genome : official journal of the International Mammalian Genome Society · 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
17 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUNDWolfram syndrome is a rare ER disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there is no treatment for Wolfram syndrome, preclinical studies in cell and rodent models suggest that therapeutic strategies targeting ER calcium homeostasis, including dantrolene sodium, may be beneficial.METHODSBased on results from preclinical studies on dantrolene sodium and ongoing longitudinal studies, we assembled what we believe is the first-ever clinical trial in pediatric and adult Wolfram syndrome patients with an open-label phase Ib/IIa trial design. The primary objective was to assess the safety and tolerability of dantrolene sodium in adult and pediatric Wolfram syndrome patients. Secondary objectives were to evaluate the efficacy of dantrolene sodium on residual pancreatic β cell functions, visual acuity, quality-of-life measures related to vision, and neurological functions.RESULTSDantrolene sodium was well tolerated by Wolfram syndrome patients. Overall, β cell functions were not significantly improved, but there was a significant correlation between baseline β cell functions and change in β cell responsiveness (R2, P = 0.004) after 6-month dantrolene therapy. Visual acuity and neurological functions were not improved by 6-month dantrolene sodium. Markers of inflammatory cytokines and oxidative stress, such as IFN-γ, IL-1β, TNF-α, and isoprostane, were elevated in subjects.CONCLUSIONThis study justifies further investigation into using dantrolene sodium and other small molecules targeting the ER for treatment of Wolfram syndrome.TRIAL REGISTRATIONClinicalTrials.gov identifier NCT02829268FUNDINGNIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK112921, DK113487, DK020579), NIH/National Center for Advancing Translational Sciences (NCATS) (TR002065, TR000448), NIH training grant (F30DK111070), Silberman Fund, Ellie White Foundation, Snow Foundation, Unravel Wolfram Syndrome Fund, Stowe Fund, Eye Hope Foundation, Feiock Fund, Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from NIH/NCATS, Bursky Center for Human Immunology & Immunotherapy Programs.
Indexed as
Identifiers
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.