Target ALS Biomarker Study; Longitudinal Biofluids, Clinical Measures, and At Home Measures
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Amyotrophic Lateral Sclerosis, Movement Disorders, Degenerative Disorder, Motor Neuron Disease. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Colombia, Puerto Rico
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Target ALS Biomarker Study; Longitudinal Biofluids, Clinical Measures, and At - Home Measures
Overview
The goal of the study is to generate a biorepository of longitudinal biofluids-blood (plasma and serum), cerebral spinal fluid (CSF) and urine linked to genetics and longitudinal clinical information that are made available to the research community. To accomplish these goals, we will enroll 800 Amyotrophic Lateral Sclerosis (ALS) patients and 200 healthy controls from sites globally, over a 5 year time frame. Additionally, speech and motor function and spirometry measures will be collected bi-weekly in a subset of participants. ALS participants will be asked to come to the clinic for 5 study visits approximately every 4 months. Healthy participants will be coming for 2 study visits with a 12-month interval between visits. These samples and clinical information will be stored in a de-identified manner and made available for investigators to use in future research studies.
Detailed description
An industry wide survey performed by Dr. Lyle Ostrow at Johns Hopkins University indicated that longitudinal biofluids linked to detailed clinical information are critical to continued drug development for amyotrophic lateral sclerosis (ALS), with CSF being the top biofluid often lacking in longitudinal sample biorepositories. There have been prior efforts for longitudinal collection of biofluids matched to clinical information, but those sample sets are limited in size and quickly utilized by the research community. Based upon input from industry leaders, we propose the creation of a Target ALS longitudinal biofluids biorepository linked to patient genetic and clinical information.
Given the heterogeneous clinical and biologic nature of ALS, a repository of longitudinal samples linked to clinical and genetic information is essential to help identify and verify ALS biomarkers (1,2). Recent studies to identify ALS biomarkers have used longitudinal samples from either the sporadic patient population or from those that harbor genetic mutations known to cause ALS but are not yet symptomatic (3,4). Beyond exploring the relationship between known causative genes and candidate biomarkers, the Target ALS Postmortem Core has collected postmortem ALS tissue samples that have been used to generate large transcriptomic databases that are linked to whole genome sequencing information. These data have been valuable at finding new subtypes of ALS linked to transcriptomic profiles from the tissue samples (5). The current study utilizes some of the medical centers participating in the Target ALS Postmortem Core to create a longitudinal biofluids repository form living ALS patients and health controls. A select number of participating sites will have a portion of ALS participants (approx. 150) have the option to take part in at home speech measures. Additionally, a select number of participating sites will also take part in at- home spirometry measures for approximately 100 ALS participants and approximately 50 healthy case control participants, for a total of 150 participants. The added feature of these at- home measures are to further evaluate the potential for at home measures in future clinical trials and ability to obtain enriched speech and vital capacity measures to correlate to downstream biomarker studies using biofluid or genetic data. There is a growing interest in the use of at home speech analytics to classify and monitor ALS patients, with recent studies indicating the value for these at home measures in both clinical research and clinical trial settings (6-8). Our study will not only expand upon these early findings but also include at home spirometry measures of vital capacity to evaluate the ability to obtain reliable vital capacity measures at home.
Our proposed study will provide valuable longitudinal biofluids linked to clinical information, genetic data, at-home speech measures, and vital capacity measures for use in future research studies. Target ALS has planned to generate proteomic, lipidomic and metabolomic datasets using the longitudinal biofluids collected in this study. Inclusion of samples with racial and ethnic diversity will further strengthen study outcomes to be applied to ALS communities more broadly. These de-identified samples and clinical information will be available to investigators throughout the world to enhance ALS research and ultimately improved treatments for ALS. There is a long history of benefit for biorepositories with linked clinical data to be instrumental in research progress. Most studies that identify biomarkers or validate biomarkers for human diseases typically require banked samples that are linked to clinical information to determine sensitivity and specificity of the biomarker for that disease or to demonstrate change over the course of the disease.
Primary outcome measures
- Biofluid Biorepository [Time frame: + 3.5 Years]
Eligibility criteria
ALS Participants:
- Age 18 or older.
- A diagnosis of ALS in accordance with Gold Coast criteria.
- Full Vital Capacity (FVC) of ≥30% or at the discretion of the Principal Investigator for the participant's predicted value for gender, height, and age at the time of screening.
- Ability to provide informed consent and understand the purpose and risks of the study.
- Ability to comply with study procedures and assessments, in the opinion of the Principal Investigator.
Healthy Control Participants:
- Age 18 or older.
- No history of neurological disease, in the opinion of the Principal Investigator.
- No known ALS- associated genetic mutations at the time of consent.
- Ability to provide informed consent and understand the purpose and risks of the study.
- Ability to comply with study procedures and assessments, in the opinion of the Principal Investigator.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Other
Study locations
United States · 10 centers
- Barrow Neurological Institute — Phoenix
- University of California San Diego — San Diego
- Georgetown University — Georgetown
- Mayo Clinic — Jacksonville
- Northwestern University — Chicago
- Massachusetts General Hospital — Boston
- Washington University — St Louis
- Columbia University — New York
- … and 2 more centers
Colombia · 1 center
- Instituto Roosevelt — Bogotá
Puerto Rico · 1 center
- CHALS-CCT UPR MScience — San Juan
Publications
- Chipika RH, Finegan E, Li Hi Shing S, Hardiman O, Bede P. Tracking a Fast-Moving Disease: Longitudinal Markers, Monitoring, and Clinical Trial Endpoints in ALS. Front Neurol. 2019 Mar 19;10:229. doi: 10.3389/fneur.2019.00229. eCollection 2019. PMID 30941088
- Benatar M, Wuu J, Lombardi V, Jeromin A, Bowser R, Andersen PM, Malaspina A. Neurofilaments in pre-symptomatic ALS and the impact of genotype. Amyotroph Lateral Scler Frontotemporal Degener. 2019 Nov;20(7-8):538-548. doi: 10.1080/21678421.2019.1646769. Epub 2019 Aug 21. PMID 31432691
- Huang F, Zhu Y, Hsiao-Nakamoto J, Tang X, Dugas JC, Moscovitch-Lopatin M, Glass JD, Brown RH Jr, Ladha SS, Lacomis D, Harris JM, Scearce-Levie K, Ho C, Bowser R, Berry JD. Longitudinal biomarkers in amyotrophic lateral sclerosis. Ann Clin Transl Neurol. 2020 Jul;7(7):1103-1116. doi: 10.1002/acn3.51078. Epub 2020 Jun 9. PMID 32515902
- Tam OH, Rozhkov NV, Shaw R, Kim D, Hubbard I, Fennessey S, Propp N; NYGC ALS Consortium; Fagegaltier D, Harris BT, Ostrow LW, Phatnani H, Ravits J, Dubnau J, Gale Hammell M. Postmortem Cortex Samples Identify Distinct Molecular Subtypes of ALS: Retrotransposon Activation, Oxidative Stress, and Activated Glia. Cell Rep. 2019 Oct 29;29(5):1164-1177.e5. doi: 10.1016/j.celrep.2019.09.066. PMID 31665631
- Vieira H, Costa N, Sousa T, Reis S, Coelho L. Voice-Based Classification of Amyotrophic Lateral Sclerosis: Where Are We and Where Are We Going? A Systematic Review. Neurodegener Dis. 2019;19(5-6):163-170. doi: 10.1159/000506259. Epub 2020 Mar 3. PMID 32126556
- Barnett C, Green JR, Marzouqah R, Stipancic KL, Berry JD, Korngut L, Genge A, Shoesmith C, Briemberg H, Abrahao A, Kalra S, Zinman L, Yunusova Y. Reliability and validity of speech & pause measures during passage reading in ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2020 Feb;21(1-2):42-50. doi: 10.1080/21678421.2019.1697888. Epub 2019 Dec 6. PMID 32138555
- Rutkove SB, Narayanaswami P, Berisha V, Liss J, Hahn S, Shelton K, Qi K, Pandeya S, Shefner JM. Improved ALS clinical trials through frequent at-home self-assessment: a proof of concept study. Ann Clin Transl Neurol. 2020 Jul;7(7):1148-1157. doi: 10.1002/acn3.51096. Epub 2020 Jun 9. PMID 32515889
- Quinn C, Macklin EA, Atassi N, Bowser R, Boylan K, Cudkowicz M, Fournier C, Ladha SS, Lacomis D, Berry J. Post-lumbar puncture headache is reduced with use of atraumatic needles in ALS. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):632-4. doi: 10.3109/21678421.2013.808227. Epub 2013 Jul 8. No abstract available. PMID 23834161
Identifiers
NCT: NCT05137665 · 21-500-101-70-09