Phenotype, Genotype & Biomarkers in ALS and Related Disorders

NCT ID: NCT02327845

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 700 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2026-08-31

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.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

Unaffected

Unaffected family members of enrolled affected individuals.

No interventions assigned to this group

Eligibility Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: collaborator

ALS Association

OTHER

Sponsor Role: collaborator

University of Miami

OTHER

Sponsor Role: lead

Responsible Party

Michael Benatar

Chief of the Neuromuscular Division, Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Benatar, DPhil

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

Stanford University

Palo Alto, California, 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 Miami

Miami, Florida, United States

University of Iowa

Iowa City, Iowa, United States

Kansas University Medical Center (KUMC)

Kansas City, Kansas, United States

Twin Cities ALS Research Consortium

Minneapolis, Minnesota, United States

Wake Forest University

Winston-Salem, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, 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 Virginia (UVA)

Charlottesville, Virginia, United States

Eberhard Karls University of Tübingen

Tübingen, , Germany

University of Cape Town

Cape Town, , South Africa

Countries

United States; Germany; South Africa

References

Benatar M, Macklin EA, Malaspina A, Rogers ML, Hornstein E, Lombardi V, Renfrey D, Shepheard S, Magen I, Cohen Y, Granit V, Statland JM, Heckmann JM, Rademakers R, McHutchison CA, Petrucelli L, McMillan CT, Wuu J; CReATe Consortium PGB1 Study Investigators. Prognostic clinical and biological markers for amyotrophic lateral sclerosis disease progression: validation and implications for clinical trial design and analysis. EBioMedicine. 2024 Oct;108:105323. doi: 10.1016/j.ebiom.2024.105323. Epub 2024 Sep 12.

Reference Type: DERIVED

PMID: 39270623 (View on PubMed)

Benatar M, Macklin EA, Malaspina A, Rogers ML, Hornstein E, Lombardi V, Renfrey D, Shepheard S, Magen I, Cohen Y, Granit V, Statland JM, Heckmann JM, Rademakers R, McHutchison CA, Petrucelli L, McMillan CT, Wuu J. Prognostic Clinical and Biological Markers for Amyotrophic Lateral Sclerosis Disease Progression: Validation and Implications for Clinical Trial Design and Analysis. medRxiv [Preprint]. 2024 Aug 13:2024.08.12.24311876. doi: 10.1101/2024.08.12.24311876.

Reference Type: DERIVED

PMID: 39185513 (View on PubMed)

Other Identifiers

U54NS092091

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20160603

Identifier Type: -

Identifier Source: org_study_id