Trial reportMovement disorders : official journal of the Movement Disorder Society2022
mTOR Inhibition with Sirolimus in Multiple System Atrophy: A Randomized, Double-Blind, Placebo-Controlled Futility Trial and 1-Year Biomarker Longitudinal Analysis.
Trial report in Movement disorders : official journal of the Movement Disorder Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03589976 (A Single Center Randomized,Double Blind, Placebo-controlled Futility Trial to Determine if Sirolimus is of Sufficient Promise to Slow the Progression of Multiple System Atrophy), which is not on this map. Cited by 28 papers.
What it found
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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 Single Center Randomized,Double Blind, Placebo-controlled Futility Trial to Determine if Sirolimus is of Sufficient Promise to Slow the Progression of Multiple System Atrophy
Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Neuron-derived extracellular vesicles to examine brain mTOR target engagement with sirolimus in patients with multiple system atrophy.Parkinsonism & related disorders · 2023Trial
- Use of blood-based neurofilament light chain as an endpoint in clinical trials of neurodegenerative conditions: a scoping review.Journal of neurology · 2026Article
- Plasma Neurofilament Light Chain as a Biomarker for Motor Progression and Disease Milestones in Multiple System Atrophy: An Updated Prospective Cohort Study.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Pharmacokinetic analysis of intermittent rapamycin administration in early-stage Alzheimer's Disease.GeroScience · 2026Article
- The role of neuro-imaging in multiple system atrophy.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Organelle resilience as a comparative blueprint for longevity.EMBO molecular medicine · 2026Review
- Drug repurposing for disease-modifying effects in multiple system atrophy.Translational neurodegeneration · 2026Review
- Multiple System Atrophy Combined Outcome Assessment (MuSyCA): process, format, and validation plan.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Article
- Treatment of primary adult-onset neurodegenerative cerebellar ataxias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Disease Progression in Multiple System Atrophy: The ASPIRE Multi-Modal Biomarker Study.Annals of neurology · 2026Article
- Multiple system atrophy: advances in pathogenesis and emerging therapeutic strategies.Journal of neurology · 2025Review
- Autophagy-Lysosome Pathway in Multiple System Atrophy Pathogenesis: The Best Is Yet to Come.International journal of molecular sciences · 2025Review
- Autophagy-Targeting Nanomedicine: Strike at the Heart of the Cancer via Precise Modulation of Autophagy.Exploration (Beijing, China) · 2025Review
- Dual Roles of Autophagy in Radiation-Induced Brain Injury: Mechanistic Insights and Therapeutic Implications.CNS neuroscience & therapeutics · 2025Review
- Dysregulation of autophagy during photoaging reduce oxidative stress and inflammatory damage caused by UV.Frontiers in pharmacology · 2025Review
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- FOXO1-mTOR pathway in vascular pericyte regulates the formation of type H vessels to control bone metabolism.Journal of orthopaedic translation · 2024Article
- Autophagy and autophagic cell death in sepsis: friend or foe?Journal of intensive care · 2024Review
- Recent Advances in Clinical Trials in Multiple System Atrophy.Current neurology and neuroscience reports · 2024Review
- Biomarkers for parkinsonian disorders in CNS-originating EVs: promise and challenges.Acta neuropathologica · 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
15 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMultiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by the aggregation of α-synuclein in glia and neurons. Sirolimus (rapamycin) is an mTOR inhibitor that promotes α-synuclein autophagy and reduces its associated neurotoxicity in preclinical models.
objectiveTo investigate the efficacy and safety of sirolimus in patients with MSA using a futility design. We also analyzed 1-year biomarker trajectories in the trial participants.
methodsRandomized, double-blind, parallel group, placebo-controlled clinical trial at the New York University of patients with probable MSA randomly assigned (3:1) to sirolimus (2-6 mg daily) for 48 weeks or placebo. Primary endpoint was change in the Unified MSA Rating Scale (UMSARS) total score from baseline to 48 weeks. (ClinicalTrials.gov NCT03589976).
resultsThe trial was stopped after a pre-planned interim analysis met futility criteria. Between August 15, 2018 and November 15, 2020, 54 participants were screened, and 47 enrolled and randomly assigned (35 sirolimus, 12 placebo). Of those randomized, 34 were included in the intention-to-treat analysis. There was no difference in change from baseline to week 48 between the sirolimus and placebo in UMSARS total score (mean difference, 2.66; 95% CI, -7.35-6.91; P = 0.648). There was no difference in UMSARS-1 and UMSARS-2 scores either. UMSARS scores changes were similar to those reported in natural history studies. Neuroimaging and blood biomarker results were similar in the sirolimus and placebo groups. Adverse events were more frequent with sirolimus. Analysis of 1-year biomarker trajectories in all participants showed that increases in blood neurofilament light chain (NfL) and reductions in whole brain volume correlated best with UMSARS progression.
conclusionsSirolimus for 48 weeks was futile to slow the progression of MSA and had no effect on biomarkers compared to placebo. One-year change in blood NfL and whole brain atrophy are promising biomarkers of disease progression for future clinical trials. © 2022 International Parkinson and Movement Disorder Society.
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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.