Genomic Translation for Amyotrophic Lateral Sclerosis Care (GTAC)

• ClinicalTrials.gov Identifier: NCT02795897
• Recruitment Status: Completed
• First Posted: June 10, 2016
• Last Update Posted: August 19, 2022
• Sponsor: Columbia University
• Collaborators: ALS Association; Biogen
• Information provided by (Responsible Party): Columbia University

Study Description

Brief Summary:

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.

Condition or disease
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 Design

• Study Type: Observational
• Actual Enrollment: 254 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Genomic Translation for Amyotrophic Lateral Sclerosis Care
• Actual Study Start Date: June 8, 2016
• Actual Primary Completion Date: July 27, 2021
• Actual Study Completion Date: June 29, 2022

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Correlation of DNA genotype with ALS phenotypes [ Time Frame: 36 months ]
   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.
2. Correlation of gene expression in blood with ALS phenotypes [ Time Frame: 36 months ]
   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.

Biospecimen Retention:   Samples With DNA

DNA, RNA and Peripheral blood mononuclear cells (PBMCs)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

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).

Contacts and Locations

Locations

United States, California

Cedar Sinai Medical Center

Los Angeles, California, United States, 90048

United States, Colorado

University of Colorado School of Medicine

Aurora, Colorado, United States, 80045

United States, Michigan

Univeristy of Michigan

Ann Arbor, Michigan, United States, 48104

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

United States, New York

Columbia University

New York, New York, United States, 10032

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27705

United States, Oregon

Oregon Health & Sciences University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Penn State College of Medicine

Hershey, Pennsylvania, United States, 17033

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

United States, Texas

Houston Methodist Neurological Institute

Houston, Texas, United States, 77030

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84112

United States, Washington

University of Washington

Seattle, Washington, United States, 98195

United Kingdom

The University of Edinburgh

Edinburgh, United Kingdom

Sponsors and Collaborators

Columbia University

ALS Association

Biogen

Investigators

• Principal Investigator: Matthew Harms, MD; Columbia University

More Information

• Responsible Party: Columbia University
• ClinicalTrials.gov Identifier: NCT02795897
• Other Study ID Numbers: AAAQ7026
• First Posted: June 10, 2016
• Last Update Posted: August 19, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Time Frame: At the end of the study.
• 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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Columbia University:

genetics; genomics; amyotrophic lateral sclerosis (ALS); primary lateral sclerosis (PLS); progressive muscular atrophy (PMA); motor neuron disease

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases