Clinical trial NCT02795897: Genomic Translation for Amyotrophic Lateral Sclerosis Care
Official title: Genomic Translation for Amyotrophic Lateral Sclerosis Care
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: ALS
Keywords: genetics
genomics
amyotrophic lateral sclerosis (ALS)
primary lateral sclerosis (PLS)
progressive muscular atrophy (PMA)
motor neuron disease
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: ALS Association
name: Biogen
First posted: 2016-06-10
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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).

Primary outcomes:
measure: Correlation of DNA genotype with ALS phenotypes
timeFrame: 36 months
measure: Correlation of gene expression in blood with ALS phenotypes
timeFrame: 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedar Sinai Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Ann Arbor
country: United States
facility: Univeristy of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Columbia University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Edinburgh
country: United Kingdom
facility: The University of Edinburgh
Study officials:
affiliation: Columbia University
name: Matthew Harms, MD
role: PRINCIPAL_INVESTIGATOR
References: