TRIAL READY (Clinical Trial Readiness)

This study, being conducted under the auspice of the CReATe Consortium, will enroll patients with ALS and related disorders as well as healthy controls, with the goal of facilitating clinical validation of leading biological-fluid based biomarker candidates that may aid therapy development for patients with ALS and related disorders.

Study Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis; Primary Lateral Sclerosis; Frontotemporal Dementia; Progressive Muscular Atrophy; ALS-Frontotemporal Dementia

Detailed Description

This multi-center study aims to clinically validate leading biological-fluid-based biomarker candidates as potential prognostic and pharmacodynamic biomarkers that have the potential to facilitate therapy development for patients with ALS and related disorders. Biomarker candidates that will be considered include: urinary p75 neurotrophin receptor extracellular domain (p75ECD), blood and cerebrospinal fluid (CSF) phosphorylated neurofilament heavy (pNfH), blood and CSF neurofilament light (NfL) and, in the population with a C9orf72 hexanucleotide repeat expansion, peripheral blood mononuclear cell (PBMC) and CSF levels of the dipeptide repeat protein poly(GP). In pursuit of these goals, the CReATe Consortium is already collecting longitudinal biological samples from patients with ALS and related disorders through the ongoing Phenotype-Genotype-Biomarker (PGB) study. TRIAL READY aims to identify additional patients with the C9orf72 hexanucleotide repeat expansion mutation (HREM), the most common genetic cause of ALS, who may be further followed through the PGB study. This study will also enroll and longitudinally evaluate a cohort of age- and gender-match healthy controls.

• Study Type: Observational
• Enrollment (Estimated): 610

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with ALS or a related neurodegenerative disorder, including FTD, ALS-FTD, PLS and PMA. Individuals never diagnosed with and not at particular risk of developing ALS or a related disorder.

Description

Inclusion Criteria:

• Member of at least one of the following categories:

  1. Individuals with a clinical diagnosis of ALS or a related disorder, including FTD, ALS-FTD, PLS, and PMA.
  2. Individuals never diagnosed with and not at particular risk of developing ALS or a related disorder.
• Able and willing to comply with relevant procedures.

Exclusion Criteria:

• A condition or situation which, in the PI's opinion, could confound the study finding or may interfere significantly with the individual's participation and compliance with the study protocol. This includes (but is not limited to) neurological, psychological and/or medical conditions.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Affected; Affected with ALS or a related disorder, including ALS-FTD, FTD, PLS, and PMA.
Healthy Controls; Those never diagnosed with and not at particular risk for developing ALS or a related disorder.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal trajectories (and variability) of leading biological-fluid biomarker candidates.	In a population of patients with ALS and related disorders who would meet typical clinical trial eligibility, this study aims to define the natural history (and variability) of urinary neurotrophin receptor extracellular domain (p75ECD); blood and cerebrospinal fluid (CSF) neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH); and among patients with the C9orf72 hexanucleotide repeat expansion mutation (HREM), CSF and peripheral blood mononuclear cell (PBMC) poly(GP).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic utility of leading biological-fluid biomarker candidates.	In a population of patients with ALS and related disorders who would meet typical clinical trial eligibility, quantify the prognostic value that baseline biomarker levels add to readily available clinical factors that are known to predict prognosis.	12 months

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Michael Benatar, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2019
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: February 27, 2019
• First Submitted That Met QC Criteria: April 10, 2019
• First Posted (Actual): April 12, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Atrophy; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Dementia; Muscular Atrophy; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Muscular Atrophy, Spinal
• Other Study ID Numbers: 20180908; U01NS107027 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No