Target ALS Biomarker Study; Longitudinal Biofluids, Clinical Measures, and At Home Measures

Amyotrophic Lateral Sclerosis Clinical Trial

— TALSLB  

Official title:

Target ALS Biomarker Study; Longitudinal Biofluids, Clinical Measures, and At - Home Measures

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05137665
• Other study ID #: 21-500-101-70-09
• Status: Recruiting
• Start date: January 1, 2021
• Est. completion date: December 31, 2031

Study information

• Verified date: November 2023
• Source: Target ALS Foundation, Inc.
• Contact: Manish Raisinghani, MBBS PhD
• Phone: 332-333-4140
• Email: manish.raisinghani[@]targetals.org
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Brief Summary: The goal of the study is to generate a biorepository of longitudinal 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 200 Amyotrophic Lateral Sclerosis (ALS) patients and 80 healthy controls from multiple sites, over a 5 year time frame. Additionally, speech measures will be collected on weekly basis at home for all participants. The measurements are performed using a speech recording application installed on their personal device. For a subset of both ALS and healthy participants, we will also collect at-home vital capacity on a weekly basis. It is expected that increased frequency data sampling of these outcome measures will help in better tracking of disease progression. Biofluids and clinical information are collected over a 20-month time frame for each individual enrolled in the research study. ALS participants will be coming to clinic for 5 study visits with a 4-month interval between visits. 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.

Description:

An industry wide survey performed by Dr. Lyle Ostrow at Johns Hopkins University indicated that longitudinal bio-fluids 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 (see https://cdmrp.army.mil/alsrp/resources/Biorepositories_biofluids_celllines for a listing of ALS biorepositories), 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. 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. Beyond exploring the relationship between known causative genes and candidate biomarkers, the Target ALS Postmortem Core has collected postmortem ALS tissue samples linked to whole genome sequencing information that have been valuable at finding new subtypes of ALS linked to transcriptomics profiles from the tissue samples. The current study utilizes medical centers participating in the Target ALS Postmortem Core to create a longitudinal biofluids repository from living patients and healthy controls. Given the impact of COVID-19 on ALS clinical research studies and clinical trials, all participants will participate in at home speech measures on a weekly basis and we will also enroll 100 ALS and 30 healthy control participants for at home measures of vital capacity that are completed once every two weeks. The added feature of these at home measures is 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. 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 and vital capacity measures for use in future research studies. 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/specificity of the biomarker for that disease or to demonstrate change over course of disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: December 31, 2031
• Est. primary completion date: December 31, 2031
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion ALS participants:

1. Age 18 or older.

2. Ability to understand the purpose and risks of the study, provide informed consent and comply with trial procedures.

3. Diagnosis of ALS according to revised EEC, including suspected, possible, probable (+/- laboratory supported), and definite.

4. Vital capacity (VC) at least 50% predicted value for gender, height and age at screening

5. In the opinion of the study physician, able to tolerate study procedures, including lumbar puncture, for the duration of the study.

6. A Score of 2 or more on item one (SPEECH) of the ALSFRS-R scale.

7. Subjects medically able to undergo lumbar puncture (LP) as determined by the investigator 15 (i.e.: no bleeding disorder, allergy to local anesthetics, a skin infection at or near the LP site, or evidence of high intracranial pressure).

8. Access to a smartphone or tablet, and internet access at home.

Inclusion Healthy participants:

1. Age 18 or older.

2. Capable of providing informed consent and complying with trial procedure.

3. No history of neurological disease, as determined by the investigator.

4. Individuals that harbor known genetic mutations that cause ALS yet are asymptomatic can also be enrolled in the Healthy participant cohort.

5. Access to a smartphone or tablet, and internet access at home.

Exclusion ALS and Healthy participants:

1. Any known or suspected abnormal CSF pressure or intracranial/intraspinal tumors

2. Use of anticoagulant medication (eg. warfarin, dalteparin, enoxaparin, rivaroxaban, fondaparinux, dabigatran) that cannot be safely withheld until coagulation parameters have normalized prior to lumbar puncture and for up to a week following the lumbar puncture.

3. Blood dyscrasia, abnormal bleeding diathesis, or the use of dialysis for renal failure.

4. Clinical judgment of the Site Investigator that the participant would be unable to undergo multiple lumbar punctures.

5. Inability to perform at home speech measures using an app on a patient device (phone or iPad)

Individuals participating in other clinical research studies will be eligible to participate in this study. ALS patients on any currently approved therapies (riluzole, edaravone) are eligible to participate and continue their medications throughout this study.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Degenerative Disorder
• Motor Neuron Disease
• Movement Disorders
• Sclerosis

Locations

Country	Name	City	State
United States	Georgetown University	Georgetown	District of Columbia
United States	Mayo Clinic	Jacksonville	Florida
United States	Columbia University	New York	New York
United States	Temple University	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Washington University	Saint Louis	Missouri
United States	University of California San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Target ALS Foundation, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (10)

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. — View Citation

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. — View Citation

Bowser R, Turner MR, Shefner J. Biomarkers in amyotrophic lateral sclerosis: opportunities and limitations. Nat Rev Neurol. 2011 Oct 11;7(11):631-8. doi: 10.1038/nrneurol.2011.151. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Ann Clin Transl Neurol. 2021 Aug;8(8):1770. — View Citation

Schievink WI. Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006 May 17;295(19):2286-96. doi: 10.1001/jama.295.19.2286. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biofluid Biorepository	This project will create a biorepository of longitudinal biofluid samples, linked to clinical measures, and at home measures	+ 3.5 Years