This study is currently recruiting participants.
Amyotrophic lateral sclerosis (ALS) is an inherited disease that damages certain nerve cells in the brain and spinal cord. People who have the gene variant that causes ALS may develop the disease at any time in their lives; they are also at risk for a related disease called frontotemporal dementia (FTD). Researchers want to find people who have genes that put them at risk for ALS and FTD. They also want to learn more about how the diseases develop.
To collect blood and spinal fluid samples, as well as other data, from people who are at risk for ALS or FTD.
Adults aged 18 years and older who are genetically at risk for ALS or FTD.
Participants will be screened. They will have several tests and procedures:
Blood will be drawn. Some blood will be used for genetic testing. Participants may opt to meet with a genetic counselor to talk about the results.
A neurological exam will assess the participant's senses, reflexes, strength, balance, eyes, and coordination.
Muscle strength will be measured with a device held against parts of the body.
Cognitive tests will assess the participant s memory and thinking.
Speech recordings will be made using an app. Tasks will include reading standard phrases, remembering words, and recording specific sounds.
Questionnaires will ask about their health, environment, and lifestyle.
A lumbar puncture is optional. A needle will be inserted into the space around the spinal cord to withdraw a fluid sample.
Participants will have 6 remote follow-up visits, 1 every 4 months. They will answer questions and record speech and memory tasks.
Participants will have 3 more clinic visits, 1 every 12 months. Tests above will be repeated.
INCLUSION CRITERIA:
Inclusion Criteria for PREVENT ALL ALS
1) Age 18 years or older
2) Capable of providing informed consent
3) Willing to follow study procedures
4) Genetically at risk for ALS based on one of the following criteria:
a. Known carrier of any ALS causative gene variant (1)
OR
b. First-degree relative of a known or obligate carrier of any ALS causative gene variant (regardless of whether ALS or FTD has actually been symptomatic in the family)
OR
c. First-degree relative (parent, sibling or child) with ALS and/or FTD and a "compelling family history" of ALS/FTD, regardless of whether genetic testing has occurred in symptomatic family members. A "compelling family history" is defined as a pedigree with at least 2 close relatives who had ALS or FTD, with at least one of those family members having had ALS.
OR
d. A compelling family history that the SI and central PREVENT team agree puts the participant at an increased risk of developing ALS/FTD and should be included in the study.
5) Access to a smartphone, computer, or tablet, and internet (need not be in the home - access to a public library or other available computer with internet connection is sufficient)
(1) Gene Eligibility Criteria: Gene is ranked as ClinGen Definitive or Strong Classification and Variant is Classified as Pathogenic or Likely Pathogenic by ACMG Criteria. If only the gene and not the specific variant is known to the participant, they are eligible if the gene is ranked as Definitive or Strong. If gene is not Definitive or Strong classification or Variant is classified as a variant of uncertain significance, participant s eligibility must be submitted for adjudication by PREVENT study team. If a site investigator is uncertain, they can contact the central PREVENT study team to inquire about the eligibility of a genetic variant. Please refer to the PREVENT
MOP for details on eligibility criteria and how to connect with the central PREVENT study team for review. The ClinGen website also be utilized to assess gene variants for exclusion (www.clinicalgenome.org).
Inclusion Criteria for Genetic Testing Results Sub-study
- Age 18 years of age or older
- Capable of providing informed consent
- Willing to follow study procedures
- Currently enrolled in the PREVENT ALS Study
EXCLUSION CRITERIA:
Exclusion Criteria for PREVENT ALL ALS
1. Evidence of neurological signs or symptoms concerning for ALS of FTD, at the discretion of the site investigator
2. Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, active suicidal ideation, suicide attempt, or untreated major depression <= 90 days (about 3 months) of screening, which in the opinion of the Investigator would interfere with the study procedures
3. Clinically significant, unstable medical condition (e.g., cardiovascular instability, systemic infection, untreated thyroid dysfunction, malignant and potentially progressive cancer) that would render the participant unlikely to be able to complete 12 months of follow-up, according to Investigator's judgment
Exclusion Criteria for Participants Undergoing Optional Lumbar Puncture
1. Medically unable to undergo lumbar puncture (LP) as determined by the site investigator (i.e., bleeding disorder, a skin infection at or near the LP site, known or suspected intracranial or intraspinal tumor or other cause of increased intracranial pressure).
2. Allergy to Lidocaine or other local anesthetic agents.
3. Use of anticoagulant medication or antiplatelet medications (aside from aspirin 81 mg) that cannot be safely withheld prior to lumbar puncture.
4. Blood dyscrasia, abnormal bleeding diathesis, or the use of dialysis for renal failure.
5. Current pregnancy based on participant self-report
6. Clinical judgement of the site investigator that the participant would be unable to undergo multiple lumbar punctures.
Exclusion Criteria for Genetic Testing Sub-Study
1. Presence of unstable psychiatric illness (psychosis, active suicidal ideation, suicide attempt, or untreated major depression) in whom predictive genetic testing would confer a high risk of harm, at the discretion of the site investigator
2. Individuals who have documentation of adequate clinical genetic testing to assess genetic risk for ALS