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

• ClinicalTrials.gov Identifier: NCT05137665
• Recruitment Status: Recruiting
• First Posted: November 30, 2021
• Last Update Posted: November 15, 2023
• Sponsor: Target ALS Foundation, Inc.
• Information provided by (Responsible Party): Target ALS Foundation, Inc.

Tracking Information

• First Submitted Date: November 16, 2021
• First Posted Date: November 30, 2021
• Last Update Posted Date: November 15, 2023
• Actual Study Start Date: January 1, 2021
• Estimated Primary Completion Date: December 31, 2031 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 16, 2021)

Biofluid Biorepository [ Time Frame: + 3.5 Years ]

This project will create a biorepository of longitudinal biofluid samples, linked to clinical measures, and at home measures

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Target ALS Biomarker Study; Longitudinal Biofluids, Clinical Measures, and At Home Measures
• Official Title: Target ALS Biomarker Study; Longitudinal Biofluids, Clinical Measures, and At - Home Measures
• Brief 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.

Detailed 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.

• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Other; Time Perspective: Other
• Target Follow-Up Duration: 5 Years

Biospecimen

Retention:   Samples With DNA

Description:

Participating sites will label and freeze up to two blood tubes collected from each study participant for DNA extraction and analysis. DNA extraction will be done at Barrow Neurological Institute (BNI). DNA may be stored, used in genome-wide association studies (GWAS), whole genome sequencing, exome sequencing, or for any other known or as yet undiscovered DNA analysis applicable to understanding or targeting disease, with a particular emphasis on ALS. The whole genomic sequencing will be done at the New York Genome Center (NYGC). The information from these genetic studies may be made available to collaborators in academia, not-for-profit settings, or industry for appropriate research. Results of DNA testing from this study will not go into the participant's medical record.

• Sampling Method: Non-Probability Sample
• Study Population: Clinic patients, with suspected, possible, probable-laboratory supported, and definite Amyotrophic Lateral Sclerosis, (ALS) according to revised El Escorial Criteria (EEC). Healthy volunteers will be family or friends of Clinic patients with suspected, possible probable, probable laboratory supported and definite Amyotrophic Lateral Sclerosis (ALS) according to revised El Escorial Criteria (EEC).

Condition

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

• Intervention: Not Provided

Study Groups/Cohorts

• Amyotrophic Lateral Sclerosis ALS
  Amyotrophic Lateral Sclerosis (ALS): Clinical diagnosis of ALS requires the presence of UMN and LMN involvement in different body regions and evidence of progressive spread of symptoms or signs according to EEC. ALS clinic patients with suspected, possible, probable, probable-laboratory supported, or definite ALS will be included. ALS clinic participants with suspected, possible, probable, probable-laboratory supported, and definite Amyotrophic Lateral Sclerosis (ALS) according to revised El Escorial Criteria (EEC) will participate in 5 longitudinal visits; Screening/Baseline Visit 1, and four (4) follow-up visits which will occur at approximate 4-month intervals. Upon IRB approved consent, the study participant will undergo the assessments and bio-fluid collections at each visit as outlined in the Schedule of Events.
• Healthy
  Healthy participants (family or friends) will have a neurologic exam to confirm non-neurologic disease status and will participate in 2 longitudinal visits; Screening/baseline Visit 1, and one (1) follow-up which will occur at approximate 12-month interval. Upon IRB approved consent, the study participant will undergo the assessments and bio-fluid collections at each visit as outlined in the Schedule of Events.

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 16, 2021): 280
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2031
• Estimated Primary Completion Date: December 31, 2031 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Manish Raisinghani, MBBS PhD; 332-333-4140; manish.raisinghani@targetals.org

Contact: Robert Bowser, PhD; 602-406-8989; robert.bowser@dignityhealth.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05137665
• Other Study ID Numbers: 21-500-101-70-09
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

These samples and clinical information will be stored in a de-identified manner and made available for investigators to use in future research studies.

It is expected to take approximately 5 years to complete all sample and data collection for the study. The first phase of the study will involve activating all sites participating in the study, and will take about 4 months to complete. The enrollment period is expected to be about 2-3.5 years. Active assessment for each subject will be for 16-18 months from the time of enrollment. After the end of active assessment period (5 years), the bio-samples and clinical information from the study will be made available for future research.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Greater than 5+ Years
• Access Criteria: Access available using published manuscripts and stored biofluids using the BioLims Repository.
• URL: http://targetals.org

• Current Responsible Party: Target ALS Foundation, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Target ALS Foundation, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Manish J Raisinghani, MBBS PhD; Target ALS Foundation, Inc.
• Study Director: Amy Easton, PhD; Target ALS Foundation, Inc.

• PRS Account: Target ALS Foundation, Inc.
• Verification Date: November 2023