Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis

Muscle Nerve. 2025 Nov;72(5):1108-1116. doi: 10.1002/mus.70011. Epub 2025 Aug 26.

Abstract

Introduction/aims: Expanded access protocols (EAPs) allow individuals ineligible for clinical trials to receive investigational products. EAP data can be collected in parallel to randomized clinical trials (RCTs) and serve as a source of evidence in clinical practice. Here, we present the results of a National Institutes of Health (NIH)-funded EAP for amyotrophic lateral sclerosis (ALS).

Methods: Participants received trehalose, a drug studied in a parallel RCT, for up to 24 weeks; clinical and biomarker data were collected throughout the study.

Results: Seventy participants were enrolled at 20 study centers across the United States. Treatment with trehalose did not affect the levels of neurofilament light chain [estimated flat slope per month was -0.005, SE = 0.0078; 95% CI (-0.021, 0.011)] or disease progression [estimated least square mean change of the ALS Functional Rating Scale-Revised total score and slow vital capacity (percent predicted) from baseline to Week 24 were -5.6 (0.67); 95% CI (-7.0, -4.3) and -4.53 (4.308); 95% CI (-13.55, 4.48)], respectively. No unexpected treatment-related risks were identified. Serious adverse events were deemed not related to trehalose (20 occurrences in 13 [18.6%] participants with eight deaths).

Discussion: This EAP establishes a framework for implementing multi-center EAPs that complement data collected from RCTs. Additional NIH-funded EAPs are currently underway. Data and additional serum samples collected in this study are available to the research community for further study.

Trial registration: ClinicalTrials.gov: NCT05597436.

Keywords: amyotrophic lateral sclerosis; expanded access; investigational product; motor neuron disease; trehalose.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis* / drug therapy
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurofilament Proteins / blood
  • Trehalose* / therapeutic use

Substances

  • Trehalose
  • Neurofilament Proteins

Associated data

  • ClinicalTrials.gov/NCT05597436