ALS Research Counts on You Division of Toxicology and Human Health Sciences Environmental Health Surveillance Branch Paul Mehta MD Principal Investigator National ALS Registry wwwcdcgovals ID: 774959
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Slide1
National ALS Registry ALS Research Counts on You
Division of Toxicology and Human Health Sciences
Environmental Health Surveillance Branch
Paul Mehta, MDPrincipal InvestigatorNational ALS Registrywww.cdc.gov/alsUniversity of Kansas Medical CenterDepartment of NeurologyGrand Rounds 10/20/2017
Slide2Disclosures
NoneThe findings from this presentation are of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (CDC/ATSDR).
Slide3Outline of Presentation
Registry does more than count ALS casesMethodologyPrevalence of ALS in the United StatesSurveys/Findings Notification Mechanism (Connecting PALS & Researchers)Registry publicationsNational ALS Biorepository now Live!Funding researchCDC Public Health Grand Rounds – April 18, 2017ALS CME Available2017 ActivitiesConclusions/Questions
Slide4Registry Does More than Just Count ALS Cases
ALS Research Counts on You!
Slide5U.S. ALS Registry Act
Enacted as Public Law 110-373 (October, 2008)
Directed CDC/ATSDR to create a population-based ALS registry for the U.S.
Does
not
make ALS a notifiable disease
National ALS Registry launched in Oct, 2010
Registry purposes (as specified by the Act)
Describe incidence and prevalence of ALS
Describe the demographics of ALS patients
Examine risk factors for the disease
Slide6National ALS Registry Methodology
* Medicare, Medicaid, Veterans Administration
** Algorithm: ICD code, frequency of neurological visits, Rx drug usage
Slide7Findings from the Second Report
Covers ONLY from January 1, 2012 – December 31, 2013
In 2012 and 2013, 14, 713 and 15,908 persons were identified as definite ALS, respectively.
Includes national databases and portal = Registry
Estimated
ALS prevalence
rates:
2012: 4.7 cases of ALS per 100,000 persons
2013: 5.0 cases of ALS per 100,000 persons
ALS
continues to be more common in Whites
, males,
and
persons aged from
60-69
Lowest number of
ALS,
Ages 18 – 39 and > 80 years
Males
had a higher prevalence than females (all data sources
)
Slide8Findings from the Second Report Continued
Prevalence rates by age group, 2012-2013:
Slide9Findings from the Second Report Continued
Prevalence rates by race, 2012-2013:2012: whites and blacks were 5.0 and 2.4 cases per 100,0002013: whites and blacks were 5.3 and 2.4 cases per 100,000
Slide10Third National ALS Prevalence Report
Will be published in
MMWR
Weekly Report
Cover calendar year 2014
Time line is Fall 2017
Finalizing and validating data from the National Death Index (NDI)
What’s new?
Include hospice data from Medicare
Increase case ascertainment/counts
Initial observations
Registry is capturing more ALS cases from databases
Prevalence is leveling or slightly increasing
Disease demographics and age groups affected are unchanged
DOES NOT mean the number of ALS cases is increasing in the United
States – improved case ascertainment
Slide11Risk Factor Surveys-Taken After Registration
Survey (n=17)
Release Date
No. Completed
Demographics
October, 2010
7830
Occupational history
October, 2010
7129
Military history
October, 2010
6991
Smoking and alcohol history
October, 2010
6878
Physical activity
October, 2010
6623
Family history of neuro. diseases
October, 2010
6458
Disease progression (ALSFRS)
October, 2010
6491
Clinical data (e.g., devices used, body onset)
November, 2013
2504
Open-ended etiological questions
November, 2013
2294
Lifetime residential history
May, 2014
2651
Lifetime occupational history
May, 2014
2615
Residential pesticide use
May, 2014
2448
Hobbies with toxicant exposures
August, 2014
2203
Caffeine consumption
August, 2014
2066
Reproductive history (women)
August, 2014
1171
Health insurance status
December, 2014
1765
Head
and neck injuries
December, 2014
1743
Total
(as of 10/16/2017)
---
69,860
Slide12Survey Analyses
Published preliminary results on surveys 1-6
Nearly half of survey respondents were ever smokers compared with nearly 41% of adults nationally.
The
majority were light drinkers
.
Nearly one-quarter of survey respondents were veterans compared with roughly 9% of US adults
nationally.
Industries
in which respondents were employed for the longest time were Professional and Scientific and Technical
Services.
Findings consistent with other published studies on ALS risk
factors.
Analyzing survey 7, disease progression
Examining surveys 15 and 17 (health status and clinical module)
Reviewing survey 16, open-ended questions on ALS causes
Slide13Research Notification System
Patient recruitment for research can be difficultApprox. 95% of Registry PALS want to participate in researchRegistry links PALS with scientists who are recruiting for research (e.g., clinical trials, studies)Domestic and international researchers are using the tool for recruitment purposes
Slide14Research Notification Mechanism
* Researchers will ultimately determine eligibility to participation in studies
Slide15Research Notification Mechanism
CDC IRB approvalNot neededIRB approval by applicant’s institutionSearch criteriaAgeSexTime since dx.City, state, regional, and nationalLess than 4 weeks for review/approval
Slide16Research Notifications
Study Name (
n=30)
Institution
Investigator
Risk Factor Analysis in ALS
Medical University of SC
David Stickler, MD
Phase II/III Trial of
Arimoclomol
in SOD1+ Familial ALS
University of Miami
Michael
Benatar
, MD, PhD
Mindfulness, psychological well-being, and physical degeneration in people with ALS
Harvard University
Ellen Langer, PhD
Spatial
Analysis of ALS in Florida, Ohio, New Hampshire, and Vermont
Dartmouth-Hitchcock Medical Center
Elijah Stommel, MD, PhD
Mexiletine
treatment of muscle cramps in ALS
University of California, Davis
Björn Oskarsson, MD
Epidemiologic Risk Factors &Genetics of ALS
University of Michigan
Eva Feldman, MD, PhD
Exp. Treatment of Bulbar Dysfunction in ALS
Center for Neurologic Study
Richard Smith, MD
The Natural History and Biomarkers of C9ORF72 ALS and
Frontotemporal
Dementia (FTD)
National Institutes of Health/NINDS
Mary Kay Floeter, MD, PhD
Developing a Satellite ALS Center at a Remote Site Incorporating Regional Resources &Telemedicine
University of Kentucky
Edward
Kasarskis
, MD, PhD
Evaluating
Ibudilast
MN 166 in subjects with ALS
Carolinas Neuromuscular AL Center
Benjamin Rix Brooks, MD
Slide17Research Notifications (cont.)
Study Name (
n=30)
Institution
Investigator
Prospective
Epi. Study in a Large National ALS Registry Cohort to Identify ALS Risk Factors
Columbia University Medical Center
Hiroshi Mitsumoto, MD, DSc
VA Biorepository Brain Bank ALS Study
VA Boston Healthcare System
Neil W. Kowall, MD
Questionnaire of cramps and pain in ALS
University of California, Davis
Björn
Oskarsson
, MD
Assessing pain in ALS
Penn State Hershey Medical Center
Zachary Simmons, MD
NeuRx
® Diaphragm Pacing System™ (DPS) study
Barrow Neurological Institute
Jeremy M.
Shefner
, MD, PhD
An online questionnaire for research into ALS
University of Sydney
Roger
Pamphlett
, MD, MB
ALS and
Genetic Testing: A Perspective from the ALS Community
The Ohio State University
Jennifer
Roggenbuck
,
MS
Speech Motor Impairments
MGH Institute of Health Professions
Jordan Green,
PhD
RDCRN Contact Registry for the
CReATe
Consortium
University of
Miami
Michael
Benatar
, MD, PhD
Study to Evaluate the Sensitivity, Specificity, and Overall Accuracy of an ALS Diagnostic Test
Iron Horse Diagnostics, Inc.
Andreas
Jeromin
, PhD
Phase 2
Pharmacodynamic
Study of
Ezogabine
on Neuronal Excitability in ALS
Massachusetts General Hospital
Brian J.
Wainger
, MD, PhD
Slide18Research Notifications (cont.)
Study Name (n=30)InstitutionInvestigatorVITALITY-ALS (Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices after Treatment for a Year)Cytokinetics, Inc.Jinsy Andrews, MDMethodology Study of Novel Outcome Measures to Assess Progression of ALSBiogen, Inc.Nazem Atassi, MDA Phase 2 Study of NP001 in Subjects with ALS and Evidence of Elevated Systemic InflammationNeuraltus Pharmaceuticals, IncGilbert Block, MD, PhDBiospecimen Collection to Investigate the Causes of ALSMayo Clinic JacksonvilleKevin Boylan, MDMicrobiome Assessment in People with ALSMassachusetts General Hospital - Neurological Clinical Research Institute (MGH-NCRI)Katharine Nicholson, MDALS Testing through Home-Based Outcome MeasuresBarrow Neurological InstituteJeremy Shefner, MDTreatment of FUS-Related ALS with Betamethasone – The TRANSLATE StudyUniversity of KentuckyEdward J. Kasarskis, MD, PhDDetermining the half-life of SOD1 in the CSFWashington University (St. Louis)Timothy Miller, MD, PhDMexiletine in Sporadic Amyotrophic Lateral SclerosisUniversity of WashingtonMichael D. Weiss, MD
>100,000 email notifications sent to date
Slide19Highlighted Notifications Using the Registry
Registry helped to recruit for notable clinical trials:
Cytokinetics, Inc. :
Tirasemtiv
, Phase III clinical trial; helps to reduce muscle fatigue
Neuraltus
Pharmaceuticals,
Inc
:
NP001, Phase II, helps to slow down ALS by reducing inflammation
Epidemiological/Risk Factor/Clinical
S
tudies
Columbia University:
ARREST
ALS study, examine the relationship between oxidative stress (OS) and
ALS
as well as
combined
exposures on development of ALS, including environmental, occupational, lifestyle, dietary, and psychological risk factors
.
Massachusetts General
Hospital:
m
icrobiome
assessment, role of gut microbiota in the development of diseases such as
ALS, linked to inflammation.
Barrow Neurological
Institute:
ALS testing
at home, travel requirement may prevent participation in
studies, ALS
patients will evaluate their own function at home.
Slide20Highlighted Notifications Using the Registry
Epidemiological/Risk Factor/Clinical
S
tudies
Washington University (
St.Louis
):
mutations
in the SOD1 gene are known to cause some forms of familial ALS. Researchers are developing a treatment to reduce the level of SOD1 in familial ALS, but need to know more about how long SOD1 stays in the body ("half-life") to help determine if the new treatment is effective.
University of Washington:
whether the
drug
mexiletine
works to calm over-excited nerves and brain cells in people with ALS. We hope that this will also slow down how quickly the disease advances. 60 people with ALS will be enrolled to take part in the study. Taking part means participating in up to four study visits and one telephone call over about eleven weeks.
Slide212017 Research Publications
Over 10 Peer-reviewed publications/abstracts (note Registry pays for open-access, when possible)Abstracts presented at AAN, NEALS, International ALS/MND SymposiumJournal Articles:
Slide22National ALS Biorepository is Live!
ATSDR completed 4 year biorepository pilot studyLaunched in January 2017Enrollment has begunMust enroll in the Registry to participatePast enrollees need to re-consentAnnual sample collection goals:675 in-home collections325: saliva, urine, blood (requires phlebotomist)350: saliva kits (mailed to PALS)10 post-mortem collectionsGlobal Unique Identifier (GUID)Active
Slide23National ALS Biorepository
Biorepository will significantly differ from others by:
linking extensive risk factor survey data with
biosamples
being nationally representative (e.g., beyond referral centers)
being user-friendly to PALS (e.g., use in-home phlebotomists to collect samples)
collecting specimens specifically for biorepository (i.e., not use leftover study samples to constitute biorepository)
containing pre/post mortem samples in one central biorepository
Largest collection of pristine ALS samples for research, e.g., genetics, biomarkers, disease progression.
No charge for patients and caregivers –user friendly
Slide24National ALS Biorepository Overview
Slide25Extramural Research Funding
ATSDR is funding extramural research to learn more about ALS etiology and risk factors12 research studies have been funded to dateInfo gleaned also will help ATSDR prioritize topics for future risk factor surveysFuture funding is subject to availability
Slide26Extramural ALS Research Funded by ATSDR
Study Name (n=13)
Institution
Investigator
Funding
period
Epidemiology of ALS
Harvard University
Marc Weisskopf, PhD, ScD
2012 - 2013
Large-scale genome-wide association study of ALS
National Institutes of Health
Bryan Traynor, MD, PhD
2012 - 2013
Gene-environment interactions in ALS
Northwestern Univ.
Teepu
Siddique
, MD
2012 – 2013
A Prospective Comprehensive Epidemiologic Study in a Large Cohort in The National ALS Registry: A Step to Identify ALS Risk Factors
Columbia University Medical Center
Hiroshi
Mitsumoto
, MD, DSc
2013 – 2017
Identification and Validation of ALS Environmental Risk Factors
University of Michigan
Eva Feldman, MD, PhD
2013 – 2017
Ecologic Study to Evaluate Spatial Relationships between ALS and Potential Environmental Risk Factors
Dartmouth College
Elijah W. Stommel, MD, PhD
2014 – 2016
Prospective study of biomarkers and risk factors for ALS incidence and progression
Harvard School of Public Health
Alberto
Ascherio
, MD,
DrPH
2014 – 2015
Case-Control Studies Nested in National ALS Registry to Evaluate Environmental Risks
Columbia University Medical Center
Hiroshi
Mitsumoto
, MD, DSc
2015 - 2018
Antecedent Medical Conditions and Medications: Associations with the Risk and Prognosis ALS
Stanford University
Lorene Nelson, PhD
2015 - 2018
ALS Risk in Latin Americans- A population based case control comparative study with 3 European population based cohorts
Trinity College – Dublin
, Ireland
Orla
Hardiman
, MD, PhD
2016 - 2018
A Population-Based Ohio ALS Repository and a Case-Control Study of ALS Risk Factors
Dartmouth
College
Elijah
Stommel
, MD, PhD
2016 - 2018
Environmental risk factors and gene‐environment interactions in ALS risk and progression
University of Miami
Michael
Benatar
,
MD, PhD
2016 - 2018
Identification and Characterization of Potential Environmental Risk Factors for ALS Using the ATSDR ALS Registry Cases and a Control Population
University of Pittsburgh at Pittsburgh
Evelyn O. Talbott,
DrPH
.
2017-2020
Slide27Highlighted Research
Dartmouth College:
Chemicals suggested to cause ALS are pesticides, algal blooms in lakes (“green scum”), and chemicals released by factories, contact all the people with ALS living in Northern and Central Ohio and ask them to answer a series of questions about what they may have been exposed to.
Stanford University:
There is little known about how chronic medical conditions and drugs may impact susceptibility to ALS. This study will look at the role of hyperlipidemia, diabetes, autoimmune diseases, as well as the drugs used to treat these disorders, as both risk and prognostic factors for ALS.
Trinity College-Dublin, Ireland:
The purpose of this study is to compare two populations with different genetic and environmental risks. It has been suggested that the Hispanic population in North America has lower rates of ALS. In effort to understand if and why the Hispanic population in North and South America is protected from ALS, we will compare this population to Europeans.
Slide28CDC Public Health Grand Rounds
First-ever for ALS and
ATSDR; April 18, 2017
Topic
: National Amyotrophic Lateral Sclerosis Registry: Impact, Challenges, and Future
Direction
4 speakers:
Kevin Horton,
DrPH
: history, purpose, and need for the Registry
Paul Mehta, MD: epidemiology, research initiatives, Biorepository
Edward
Kasarskis
, MD: neurologist perspective
Edward
Tessaro
: patient perspective
Viewer metrics
Over 20,000 Facebook live viewers;
Post Reach: 222,729
(287% above average reach of a Facebook post from CDC)
209,506
organic reach (total number of unique people who
received post)
Beyond the Data session archived on YouTube
Slide29ALS Continuing Education Module
1.5 contact hours of free CECourse was developed for physicians (primary care physicians and neurologists without ALS expertise) as well as other public health professionals
Slide302017 Activities
Published funding opportunity announcement (FOA)
Identify and Characterize Potential Environmental Risk Factors for Amyotrophic Lateral Sclerosis (ALS) and Evaluate Their Impact on ALS Disease Incidence and
Progression
Funded one grant
Working on new FOA for FY18, released in the Fall
Update Registry website
Responsive, mobile friendly design – user testing started
Launch September 2017
Spanish site for ALS information, registration, and completion of surveys
Developed new Registry informational video
Describe benefits and facets of the Registry to PALS/caregivers
Slide312017 Activities
3
rd
MMWR Report
Anticipated release in the fall 2017
C
alendar year 2014
Manuscripts in development
Access to ALS care, using ALSA and MDA clinic locations
ALS survival/disease progression modeling
National ALS mortality
Comparison of Registry data to state and metro data
Capture/Recapture
Educational
and promotional outreach activities to general
neurologists (non-referral)
Open-ended survey: What caused my ALS?
Continued evaluation Registry risk factor data
Currently almost 70,000 completed surveys
Slide32Summary
The National ALS Registry is:
The 1st & only population-based ALS registry for the U.S.
F
ulfilling Congressional mandate
Registry has added National ALS Biorepository
Sample collection from PALS
Sample dissemination to researchers
Registry has added GUID
Registry continues to fund research on ALS risk factors and etiology
Registry seeks to have a larger internet presence
Responsive design/web buttons
National ALS Registry continues to mature
Slide33Comments/Questions?www.cdc.gov/als
Division of Toxicology and Human Health Sciences
Environmental Health Surveillance Branch