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

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

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