Phenotype, Genotype and Biomarkers 2 (PGB2)

The purpose of this study is to learn more about amyotrophic lateral sclerosis (ALS) and other related neurodegenerative diseases, including frontotemporal dementia (FTD), primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), progressive muscular atrophy (PMA) and multisystem proteinopathy (MSP). More precisely, the investigator wants to identify the links that exist between the disease phenotype (phenotype refers to observable signs and symptoms) and the disease genotype (genotype refers to your genetic information). The investigator also wants to identify biomarkers of ALS and related diseases.

Study Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis; Primary Lateral Sclerosis; Frontotemporal Dementia; Progressive Muscular Atrophy; Hereditary Spastic Paraplegia

• Study Type: Observational
• Enrollment (Actual): 217

Contacts and Locations

Study Locations

• South Africa
  • Cape Town, South Africa
    • University of Cape Town
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Primary participants - patients that have or are suspected to have ALS or a related disease.

Secondary participants - family members of primary participants enrolled in the study

Description

Inclusion Criteria for affected individuals (primary participants) include:

• Clinical diagnosis or suspicion of ALS or a related disorder, including, but not limited to, ALS-FTD, PLS, HSP, FTD, Multisystem Proteinopathy (MSP) and PMA.
• Subject is able and willing to comply with study procedures

Exclusion Criteria for affected individuals (primary participants) include:

• Subjects with a condition or who are in a 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 -- including but not limited to neurological, psychological and/or medical conditions

Inclusion criteria for biological family members (secondary participants) include:

• Family member of an enrolled affected primary participant

Exclusion Criteria for biological family members (secondary participants) include:

• Subjects with a condition or who are in a 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 -- including but 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
Primary participants; Patients that have or are suspected to have ALS or a related neurodegenerative disease
Secondary Participants; Family members of primary participants enrolled in the study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of change in revised ALS functional rating scale (ALSFRS-R)	Prepare motor outcome measures for clinical trials in sub-populations of patients with ALS or a related disorder who have identifiable genetic causes of disease	48 months
Rates of change in Slow vital capacity (SVC)	Prepare motor outcome measures for clinical trials in sub-populations of patients with ALS or a related disorder who have identifiable genetic causes of disease	48 months
Rates of change in Spastic paraplegia rating scale (SPRS)	Prepare cognitive and behavioral outcome measures for clinical trials in sub-populations of patients with ALS or a related disorder who have identifiable genetic causes of disease	48 months
Rates of change in Edinburgh Cognitive and Behavioral ALS Screen (ECAS)	Prepare cognitive and behavioral outcome measures for clinical trials in sub-populations of patients with ALS or a related disorder who have identifiable genetic causes of disease	48 months
ALS Health Index (ALS-HI)	Validate the ALS Health Index (ALS-HI), a novel patient reported outcome (PRO) measure	48 months
Serum	Determine the diagnostic utility of serum neurofilament concentrations	48 months
Cerebrospinal Fluid (CSF)	Determine the diagnostic utility of CSF neurofilament concentrations	48 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, MD, PhD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2021
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: April 30, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: ALS; FTD; HSP; PLS; PMA; MSP
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neuromuscular Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Nervous System Malformations; Polyneuropathies; Frontotemporal Lobar Degeneration; Hereditary Sensory and Motor Neuropathy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Frontotemporal Dementia; Muscular Atrophy, Spinal; Spastic Paraplegia, Hereditary
• Other Study ID Numbers: 20200888; U54NS092091 (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