Phenotype, Genotype & Biomarkers in ALS and Related Disorders

The goals of this study are: (1) to better understand the relationship between the phenotype and genotype of amyotrophic lateral sclerosis (ALS) and related diseases, including primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), progressive muscular atrophy (PMA), and frontotemporal dementia (FTD); and (2) to develop biomarkers that might be useful in aiding therapy development for this group of disorders.

Study Overview

• Status: Enrolling by invitation
• Conditions: Amyotrophic Lateral Sclerosis; Primary Lateral Sclerosis; Frontotemporal Dementia; Progressive Muscular Atrophy; Hereditary Spastic Paraplegia; Multisystem Proteinopathy

Detailed Description

This study will recruit patients with ALS, ALS-FTD, PLS, HSP, and PMA, with a focus on incident cases. Patients with both familial and sporadic forms of these diseases will be enrolled and followed longitudinally using a standardized set of evaluations. Biological samples (blood, urine, CSF) will be collected from all study participants, and will be used for biomarker discovery and validation. Family members of affected individuals may also be enrolled and asked to contribute DNA and biological samples to aid genetic and biomarker discovery.

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany
    • Eberhard Karls University of Tübingen
• South Africa
  • Cape Town, South Africa
    • University of Cape Town
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92093
      • University of California San Diego (UCSD)
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center (CPMC)
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center (KUMC)
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Twin Cities ALS Research Consortium
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern (UTSW)
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center San Antonio (UTHSCSA)
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia (UVA)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with ALS or a related neurodegenerative disorder, including FTD, HSP, PLS, PMA and MSP. Select family members of affected participants.

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, HSP, PLS, PMA and MSP (sporadic or familial).
  2. Family member of an enrolled affected individual.
• Able and willing to comply with relevant procedures.

Exclusion Criteria:

• Affected with end or late stage disease.
• 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 any of the diseases that are the focus of study by the CReATe Consortium, including ALS, ALS-FTD, HSP, PLS, PMA and MSP.
Unaffected; Unaffected family members of enrolled affected individuals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotypic correlates of genotype	Using longitudinally collected deep phenotypic data, this project aims to define the natural history (i.e. temporal rate of disease progression) of the motor and frontotemporal system (behavior, cognition and language) phenotypes of ALS and related disorders in patients with identifiable genetic mutations.	24 months
Genetic determinants of phenotype	By combining longitudinally collected deep phenotypic data with deep genetic data (e.g. whole exome or whole genome sequencing), this project aims to define genetic variants that are associated with identifiable phenotypic features in patients with ALS and related disorders.	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	Biomarkers relevant to therapeutic development	24 months

Collaborators and Investigators

• Sponsor: University of Miami
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); St. Jude Children's Research Hospital; ALS Association; National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Michael Benatar, DPhil, University of Miami

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: December 24, 2014
• First Submitted That Met QC Criteria: December 24, 2014
• First Posted (Estimated): December 30, 2014

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: July 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: natural history, biomarkers, phenotype, genotype
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Manifestations; Mental Disorders; Pathologic Processes; Pathological Conditions, Anatomical; Neuromuscular Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Neurobehavioral Manifestations; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Nervous System Malformations; Atrophy; Communication Disorders; Polyneuropathies; Paralysis; Language Disorders; Aphasia; Speech Disorders; Frontotemporal Lobar Degeneration; Hereditary Sensory and Motor Neuropathy; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Muscular Atrophy; Muscular Atrophy, Spinal; Paraplegia; Spastic Paraplegia, Hereditary
• Other Study ID Numbers: 20160603; 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