Genomic Translation for Amyotrophic Lateral Sclerosis Care (GTAC)

The purpose of this study is to look for abnormal genes and gene expression profiles that help determine why a person develops amyotrophic lateral sclerosis (ALS) and related motor neuron diseases (MND) and why their symptoms present and progress with a particular pattern.

Study Overview

• Status: Completed
• Conditions: ALS

Detailed Description

In all patients, ALS/MND is caused by the progressive death of motor neurons. However, every patient is affected differently. Some develop symptoms in their 80's while others get sick in adolescence. Swallowing/speech are affected first in some patients, but most have weakness in their hands or feet at onset. Some individuals show very rapid progression, even as others live for decades. Finally, some patients have loss of mainly motor neurons in the brain (as in primary lateral sclerosis), while others lose mainly lower motor neurons in the spinal cord and brain stem (as in progressive muscular atrophy). Research has uncovered a few genetic factors that contribute to the variability of ALS/MND. For example, mutations in the superoxide dismutase 1 (SOD1) gene makes onset in the legs more likely and decreases the chance of developing dementia. Conversely, having a mutated C9ORF72 gene makes dementia much more likely. Uncovering additional factors causing ALS variability is an important research priority and is likely to provide clues about how to better diagnose and treat the disease.

This study is called "Genomic Translation for ALS Care" (GTAC). The investigators will analyze the genome and gene expression patterns of people with ALS/MND and carry out research on that data, finding insights that the investigators hope will translate into better care for ALS/MND patients.

• Study Type: Observational
• Enrollment (Actual): 254

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom
    • The University of Edinburgh
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedar Sinai Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Univeristy of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with ALS (meeting El Escorial criteria for definite, probable or possible ALS), or primary lateral sclerosis or progressive bulbar/muscular atrophy.

Description

Inclusion Criteria:

Study participants meeting all of the following criteria will be eligible for enrollment in GTAC:

1. Men or women of any race or ethnicity aged 18 or older
2. Diagnosis of familial or sporadic ALS (definite, probable, or possible according to El Escorial Criteria, Appendix 1), or those with primary lateral sclerosis or progressive bulbar/muscular atrophy forms of motor neuron disease. All-comers with ALS/MND should be enrolled without regard to familial vs sporadic or gene mutation status (i.e. participants with known gene mutations should still be enrolled), or phenotype.
3. Capable of providing informed consent and following study procedures (in the case that a subject lacks the ability to provide informed consent, informed consent will be sought from the subject's surrogate representative).
4. Willing to return to clinic site (or another participating center) for follow-up care.

Exclusion Criteria:

Study participants meeting any of the following criteria during screening evaluation will be excluded from enrolling in GTAC:

1. Invasive ventilation (i.e. tracheostomy) in place.
2. Non-invasive ventilation dependent (defined as >22 hours per day)
3. Pregnancy.
4. Known Human Immunodeficiency Virus (HIV) , chronic Hepatitis B, or Hepatitis C (because cells will be frozen down for future cell line generation).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of DNA genotype with ALS phenotypes	Because subjects are followed over their entire disease course and undergo whole genome sequencing of their DNA, this project will study the distinct features (progression and particular symptoms) of subjects with and without mutations in already known ALS genes.	36 months
Correlation of gene expression in blood with ALS phenotypes	Because subjects are followed over their entire disease course and undergo gene expression profiling on their blood sample, this project will study the distinct features (progression and particular symptoms) of subjects with different types of gene expression profiles.	36 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Biogen; ALS Association
• Investigators: Principal Investigator: Matthew Harms, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2016
• Primary Completion (Actual): July 27, 2021
• Study Completion (Actual): June 29, 2022

Study Registration Dates

• First Submitted: June 7, 2016
• First Submitted That Met QC Criteria: June 7, 2016
• First Posted (Estimate): June 10, 2016

Study Record Updates

• Last Update Posted (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 18, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: genetics; genomics; motor neuron disease; amyotrophic lateral sclerosis (ALS); primary lateral sclerosis (PLS); progressive muscular atrophy (PMA)
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: AAAQ7026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The investigators intend to share DNA, sequencing data, and phenotypic data broadly. Participants will be consented for sharing of GTAC data and samples with the Northeast ALS Consortium (NEALS) repository, with others carrying out ALS/MND research (including other consortia), for biomedical research in general (including use as controls and use by for-profit companies), and with Biogen Idec. Additionally, GTAC has plans to share coded genomic and clinical data with Database of Genotypes and Phenotypes (dbGaP) and a ALS/MND consortium for genomic discovery (ASLGEN). This includes sharing of genetic and phenotypic data with Biogen Idec, a pharmaceutical company that is partnering with GTAC to fund the sequencing of samples.
• IPD Sharing Time Frame: At the end of the study.
• IPD Sharing Access Criteria: The investigators intend to share DNA, sequencing data, and phenotypic data with the NEALS repository and Biogen Idec. Coded genomic and clinical data will be shared with dbGaP and ASLGEN.

Drug and device information, study documents

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