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

Authors

• Brooke Krivickas, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Erica Scirocco, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Elisa Giacomelli, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Saloni Sharma, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Molly Benson, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Mackenzie Keegan, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Jennifer Kulesa-Kelley, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Lori B. Chibnik, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Gabriella Casagrande, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Lindsay Heyd, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Marianne Chase, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Kristin Drake, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Silpa Mohapatra, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Jennifer Linn Hagar, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Meredith Gibbons Hasenoehrl, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Derek Dagostino, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Alexander V. Sherman, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Alex Leite, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Hong Yu, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Jesse Rosenthal, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Timothy Miller, Washington University School of Medicine, St. Louis, Missouri, USA.
• Alexandra McCaffrey, Sean M. Healey & AMG Center for ALS and Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• Kelly Gwathmey, Virginia Commonwealth University, Richmond, Virginia, USA.
• Eduardo Locatelli, Nova Southeastern University, Davie, Florida, USA.
• Elham Bayat, George Washington University, Washington, DC, USA.
• Daragh Heitzman, Texas Neurology, Dallas, Texas, USA.
• Eufrosina Young, Upstate Medical University, Syracuse, New York, USA.
• Namita A. Goyal, University of California Irvine, Orange, California, USA.
• Jackie Whitesell, Saint Alphonsus, Boise, Idaho, USA.
• Kevin Felice, Hospital for Special Care, New Britain, Connecticut, USA.
• Hristelina Ilieva, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Document Type

Article

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.

Medical Subject Headings

Humans; Amyotrophic Lateral Sclerosis (drug therapy); Trehalose (therapeutic use); Middle Aged; Male; Female; Aged; Disease Progression; Adult; Neurofilament Proteins (blood)

Publication Date

11-1-2025

Publication Title

Muscle & nerve

E-ISSN

1097-4598

Volume

72

Issue

5

First Page

1108

Last Page

1116

PubMed ID

40857020

Digital Object Identifier (DOI)

10.1002/mus.70011

Recommended Citation

Krivickas, Brooke; Scirocco, Erica; Giacomelli, Elisa; Sharma, Saloni; Benson, Molly; Keegan, Mackenzie; Kulesa-Kelley, Jennifer; Chibnik, Lori B.; Casagrande, Gabriella; Heyd, Lindsay; Chase, Marianne; Drake, Kristin; Mohapatra, Silpa; Hagar, Jennifer Linn; Hasenoehrl, Meredith Gibbons; Dagostino, Derek; Sherman, Alexander V.; Leite, Alex; Yu, Hong; Rosenthal, Jesse; Miller, Timothy; McCaffrey, Alexandra; Gwathmey, Kelly; Locatelli, Eduardo; Bayat, Elham; Heitzman, Daragh; Young, Eufrosina; Goyal, Namita A.; Whitesell, Jackie; Felice, Kevin; and Ilieva, Hristelina, "Multicenter Expanded Access Protocol for Research Through Access to Trehalose in People With Amyotrophic Lateral Sclerosis" (2025). Neurology. 2037.
https://scholar.barrowneuro.org/neurology/2037