The Phenotype-Genotype and Biomarker Study of the CReATe Consortium will prospectively and systematically study approximately 700 patients with amyotrophic lateral sclerosis (ALS) or a related neurodegenerative disorder such as ALS-frontotemporal dementia (FTD), primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), progressive muscular atrophy (PMA), and multisystem proteinopathy (MSP). The study is broadly inclusive, enrolling patients with both familial and sporadic forms of disease. All enrolled patients will undergo five in-person evaluations at one of the CReATe consortium clinical sites as well as annual remote evaluations. In-person evaluations will include motor, cognitive and functional assessments as well as collection of biological fluids. Remote evaluations will focus on functional status and disease staging. Family members of patients with apparently sporadic disease (i.e. no family history) may also participate through a remote-evaluation process in which they provide limited information about their medical history as well as biological samples (blood and urine). Every effort will be made to integrate study procedures into multi-disciplinary clinic visits to minimize the burden of participation on patients and their families.
ALS and related neurodegenerative disorders are currently untreatable. One important reason may be that clinical trials in the past have regarded all ALS patients, for example, as having the same disease. With the growing recognition that ALS is a heterogeneous clinical syndrome with many different causes (rather than a unitary disease with single cause), it is increasingly clear that clinical trials should rather focus on subgroups of patients with shared disease characteristics (e.g. the same genetic cause of disease, or the same biological mechanisms that cause motor neurons to become sick and die).
The goals of this study are threefold. The first is to better understand the genetic contribution to ALS and related neurodegenerative disorders. The second is to prepare for a future of clinical trials in which potential treatments will be tested in patients who share certain characteristics such as a specific genetic cause of disease. The third is to develop biological markers that will aid testing of novel therapeutics. The first two goals will be accomplished by combining detailed information about the clinical symptoms and signs of disease (i.e. phenotype) with an in-depth understanding of an individual's genetic make-up (genotype). The third goal will be accomplished by laboratory testing of biological samples (blood, urine and spinal fluid) that are collected from study participants. Although the study protocol does not specifically involve testing any new treatments, all study procedures are directly relevant to therapeutic development.
This longitudinal study will recruit approximately 700 people who are affected with ALS or a related disorder (primary participants). Patients with both familial and sporadic forms of these diseases will be enrolled. In addition, where possible, we will collect a blood sample and limited clinical information from family members of affected individuals (secondary participants); we expect to enroll ~700 secondary participants.
Study involvement (for primary participants) entails five in-person assessments over two years and annual remote assessments thereafter:
Study involvement (for secondary participants) entails a single remote assessment:
We will look at your medical records from your doctor’s office so that we can get information about your medical history.
To be eligible to participate, you must:
You are not eligible to participate if:
In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation.
University of Miami (UM)
University of Pennsylvania
University of Kansas Medical Center
Join CReATe Connect!
The purpose of the Clinical Procedures To Support Research (CAPTURE) study is to utilize information collected in the medical record to learn more about a disease called amyotrophic lateral sclerosis (ALS) and related disorders.
The study will consent patients with ALS or related disorders that are receiving care at a clinical center in the CReATe consortium that uses Epic as its electronic health record (EHR) system. The study aims to systematically gather a clinical dataset through the EHR using a standardized approach to characterize the natural history of ALS and related diseases.
A total of approximately 1,200 people will take part in this study across the United States. Those participating in the study will only have one in-person study visit which will occur at the time of their regular clinic visit. Data will also be collected from each participant’s medical records on an ongoing basis.
If you join the CAPTURE study, you will be asked to:
University of Miami
California Pacific Medical Center
ALS Forbes-Norris Center
The purpose of this study is to learn about rates of disease progression in patients with motor neuron diseases, as reported by the patients while they are outside of clinic. Another purpose of this study is to learn about clinical characteristics that patients report influence this rate of progression. All patients enrolled in CReATe Connect, a Rare Diseases Clinical Research Network (RDCRN) Contact Registry, will be invited via email to participate in this study.
Motor neuron diseases (MND) are a group of disorders with the common feature of progressive loss of motor neurons in the brain and spinal cord which lead to loss of motor functions like walking, dressing, swallowing, or breathing. The majority of patients followed in multi-disciplinary MND clinics will have a clinical diagnosis of ALS. But MND exist on a spectrum from pure upper motor dysfunction (primary lateral sclerosis, PLS or hereditary spastic paraplegia, HSP), to mixed upper and lower motor neuron dysfunction (ALS), to pure lower motor neuron involvement (progressive muscular atrophy, PMA). Some patients have memory or behavioral changes in addition to their motor limitations (ALS with frontotemporal dementia, ALS-FTD).
Functional rating scales have become the standard primary outcome measure for clinical trials of neurodegenerative diseases. The ALS Functional Rating Scale-Revised (ALSFRS-R) was designed to assess the ability of ALS patients to perform activities of daily living and to detect functional changes during clinical trials. The ALSFRS-R is quickly administered by research personnel or study staff (ten minutes) and is a rating scale that assesses capability and independence in 12 functional activities. These include six bulbar-respiratory functions, three upper extremity functions (writing, cutting food, and dressing), and three gross motor functions (walking, climbing, and turning in bed). Each activity is recorded to the closest approximation from a list of five choices, scored 0-4, with the total score ranging from 48 (normal function) to 0 (no function). The ability to use a patient-reported tool like the ALSFRS-R to assess patient function between clinic visits from the home would be a powerful new tool for clinicians to monitor the effect of interventions including: medications, orthotic devices, and respiratory or feeding support. In addition, the usefulness of a scale like the ALSFRS-R in the full range of MND is not known. We developed a new patient-reported survey which incorporates many of the key elements of the ALSFRS to be used by MND patients in between patient visits.
The research questions are:
This is a prospective 12-month study of patients with MND enrolled in CReATe Connect, an RDCRN Contact Registry. Participants will be asked to complete the survey every month for 1 year.
The survey will contain questions about participants’ diagnosis (such as age when symptoms started, where first symptoms occurred) and functional status (things like walking, eating, dressing, breathing). We will ask participants to update their functional status survey (15 questions) monthly for 1 year. Participants may choose to skip any question(s) that make them feel uncomfortable. It should take approximately 20 minutes to complete the survey the first time, then 10-15 minutes for each follow up survey.
If you have not done so already, please join CReATe Connect, a Contact Registry that has been established through the RDCRN! We will invite individuals in CReATe Connect to participate in this study.
If you have questions or concerns about this study or about the survey, please contact:
Jeffrey Statland, MD
University of Kansas Medical Center
Research Coordinator: Laura Herbelin
Callyn A. Kirk, MSPH
University of South Florida Health Informatics Institute
Amyotrophic lateral sclerosis (ALS)
ALS is a disease that causes muscle loss, paralysis (inability to move), and eventually death. The average ALS patient lives 3 to 5 years after diagnosis. There are few treatments for ALS.
The immune system is how the body fights off infection and disease. Cells called innate lymphoid cells (ILCs) are part of the human immune system. Some ALS patients have unusually high levels of ILCs.
We want to find out how ILCs work in ALS patients. We also want to know if a person’s ILCs make their ALS worse over time. We hope what we learn in this study will lead to new ALS treatments.
The immune system plays an important key role in ALS. The immune system responds to ALS in two different ways. The first response seems to be helpful, but the second response may be harmful as ALS gets worse.
ILCs might contribute to the helpful ALS response. But a very high ILC level might eventually lead to the harmful ALS response.
We will look at ILCs in ALS patients for one year. We will try to determine when their ILC levels begin to increase. We will also try to find out if ILCs are more active in ALS patients than in people without ALS.
If you decide to be in this study, we will visit you every month for a year. At each visit, we will use a needle to take about 2 teaspoons of blood from your vein. We will also call you on the phone every month to ask you about your health. You will be asked to give your informed consent to participate. The informed consent process allows you to ask questions about the study to make sure you understand what is going to happen to you.
You may be able to take part in this study if you:
You cannot take part if you:
Please Note: We will try to enroll as many ALS patients in this study as we can. But we may not be able to enroll everyone who wants to participate.
If you have questions about this study or may like to join, please contact us by phone or by e-mail:
University of Michigan at Ann Arbor
Study Coordinator: Blake Swihart
Status: Not Recruiting
This study will perform whole genome sequencing (WGS) on DNA samples previously collected from patients with ALS or a related neurodegenerative disorder on whom we have less phenotypic data than is collected through the CReATe Phenotype, Genotype, and Biomarker (PGB) protocol.
The primary objectives of this study are:
This is a retrospective study as it performs whole genome sequencing on DNA samples that have previously been collected by investigators within the CReATe Consortium.
This is a retrospective study and is not enrolling any participants prospectively.
Not open to prospective enrollment
The purpose of the St.A.R. 2 study (Study of ALS Reversals 2: Genetic Analyses) is to try to understand why reversals of amyotrophic lateral sclerosis (ALS) and primary muscular atrophy (PMA) take place. The study will be enrolling patients with ALS and/or PMA reversals to give saliva samples in order to determine if the ALS or PMA reversal is because of certain changes in the genetic code.
Amyotrophic Lateral Sclerosis (ALS) and Primary Muscular Atrophy (PMA) are devastating motor neuron diseases that typically cause rapidly progressive muscle weakness, disability and premature death. There exists a small group of patients that were previously identified in the St.A.R. 1 study (Study of ALS Reversals 1: Documentation of Known ALS Reversals), who were diagnosed with ALS or PMA, progressed for a period of time, and then significantly improved.
This is a pilot study of 34 individuals that had a reversal of ALS or PMA. Those participating in this study will provide information about themselves, their disease and their family’s medical history along with saliva samples. The study takes approximately an hour to complete and can be done remotely.
In order to participate in a study, you must personally contact the study coordinator at Duke University by phone or by e-mail. Please use the information below to ask about participation.
Duke University, Durham, North Carolina
Principal Investigator: Richard Bedlack, MD, PhD
The purpose of this study is to identify biological markers that can indicate disease severity and progression in Hereditary Spastic Paraplegia (HSP) and Primary Lateral Sclerosis (PLS). We will analyze a panel of biological markers of axonal degeneration on blood, spinal fluid and urine previously collected from patients with HSP and PLS.
Hereditary Spastic Paraplegias and Primary Lateral Sclerosis are neurodegenerative disorders primarily affecting upper motor neurons. Patients experience progressive weakness and spasticity, but may also experience additional neurological deficits. The purpose of this study is to identify biological markers in blood, spinal fluid or urine of patients with these diseases that can indicate the severity of the disease and potentially reflect or predict disease progression. These biological markers are important for future therapeutic clinical trials as they can be used to measure treatment response.
The research questions are:
This is a retrospective study as it utilizes specimens and clinical data that have already been collected and archived for future use in research under separate IRB-approved protocols by collaborators. Samples and data from about 330 individuals will be included in the study, including 250 patients and 80 healthy controls.
Not open to prospective enrollment.
The main goals of the TRIAL READY study are: (a) to enroll and follow healthy individuals with longitudinal collection of biological specimens; and (b) to offer screening for a change (mutation) in the C9ORF72 gene to all ALS and related disorder patients seen at participating centers. Patients will also be asked to return for longitudinal collection of clinical (phenotypic) data and biological specimens. The biological specimens collected from ALS patients and healthy controls will be used, along with similar data and specimens collected through other CReATe Consortium protocols, to learn more about biomarkers of ALS and related neurodegenerative diseases. A biomarker is an indicator of disease that can easily be measured. This information will be used to help advance the development of therapies for this group of disorders.
ALS and related neurodegenerative diseases are currently untreatable and continue to be resistant to the development of effective therapies. Clinical trials are hampered by a paucity of biomarkers that might provide an early indication of whether an experimental treatment is helping.
A total of about 600 people will take part in this study at sites in the United States. The study will include ~500 adults who have ALS or a related disease and ~100 healthy adult volunteers (controls).
Study participants with ALS or a related disease will have 2 in-person visits to:
Study participants who are healthy volunteers will have 5 in-person visits over one year to:
To be eligible to participate, you must be part of one of the following groups:
This study is closed to enrollment.