Phenotype, Genotype & Biomarkers in ALS and Related Disorders

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

• Registration Number: NCT02327845
• Lead Sponsor: University of Miami

Brief Summary

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.

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 Timeline

• Study First Submitted: 2014-12-24
• Study First Submitted QC: 2014-12-24
• Study First Posted: 2014-12-30
• Study Start: 2015-04
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-16
• Last Update Posted: 2024-12-17
• Primary Completion: 2025-07
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 700

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Genetic determinants of phenotype	24 months	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.
Phenotypic correlates of genotype	24 months	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.

Trial Locations

Locations (15)

Twin Cities ALS Research Consortium; 🇺🇸 Minneapolis, Minnesota, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

University of Texas Southwestern (UTSW); 🇺🇸 Dallas, Texas, United States

University of Texas Health Science Center San Antonio (UTHSCSA); 🇺🇸 San Antonio, Texas, United States

University of California San Diego (UCSD); 🇺🇸 San Diego, California, United States

California Pacific Medical Center (CPMC); 🇺🇸 San Francisco, California, United States

University of Virginia (UVA); 🇺🇸 Charlottesville, Virginia, United States

University of Miami; 🇺🇸 Miami, Florida, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Kansas University Medical Center (KUMC); 🇺🇸 Kansas City, Kansas, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

University of Cape Town; 🇿🇦 Cape Town, South Africa

Wake Forest University; 🇺🇸 Winston-Salem, North Carolina, United States

Eberhard Karls University of Tübingen; 🇩🇪 Tübingen, Germany