GTAC: Genomic Translation for Amyotrophic Lateral Sclerosis Care

Sponsor

Columbia University (Other)

Overall Status

Completed

CT.gov ID

NCT02795897

Collaborator

ALS Association (Other), Biogen (Industry)

254

Enrollment

Locations

72.7

Actual Duration (Months)

18.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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	Intervention/Treatment	Phase
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 :

Jun 8, 2016

Actual Primary Completion Date :

Jul 27, 2021

Actual Study Completion Date :

Jun 29, 2022

Outcome Measures

Primary Outcome Measures

Correlation of DNA genotype with ALS phenotypes [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.
Correlation of gene expression in blood with ALS phenotypes [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

GTAC:

Men or women of any race or ethnicity aged 18 or older
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.
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).
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:

Invasive ventilation (i.e. tracheostomy) in place.
Non-invasive ventilation dependent (defined as >22 hours per day)
Pregnancy.
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

	Site	City	State	Country	Postal Code
1	Cedar Sinai Medical Center	Los Angeles	California	United States	90048
2	University of Colorado School of Medicine	Aurora	Colorado	United States	80045
3	Univeristy of Michigan	Ann Arbor	Michigan	United States	48104
4	University of Minnesota	Minneapolis	Minnesota	United States	55455
5	Washington University	Saint Louis	Missouri	United States	63110
6	Columbia University	New York	New York	United States	10032
7	Duke University	Durham	North Carolina	United States	27705
8	Oregon Health & Sciences University	Portland	Oregon	United States	97239
9	Penn State College of Medicine	Hershey	Pennsylvania	United States	17033
10	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
11	Houston Methodist Neurological Institute	Houston	Texas	United States	77030
12	University of Utah	Salt Lake City	Utah	United States	84112
13	University of Washington	Seattle	Washington	United States	98195
14	The University of Edinburgh	Edinburgh		United Kingdom