Study of ALS Reversals 2: Genetic Analyses (StAR2)

ALS Reversals: Genetic Analyses (St.A.R. Protocol 2) RDCRN CReATe Protocol #8007

The purpose of this study is to try to understand why reversals of amyotrophic lateral sclerosis (ALS) and primary muscular atrophy (PMA) take place. The study will enroll patients with ALS 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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis; Progressive Muscular Atrophy

Detailed Description

Amyotrophic Lateral Sclerosis (ALS) is a devastating motor neuron disease that typically causes rapidly progressive muscle weakness, disability and premature death. In spite of a large number of attempted ALS trials, there are no significant disease-modifying therapies for this condition to-date.

There exists a small group of patients who meet diagnostic criteria for ALS or progressive muscular atrophy (PMA), progress for a period of time, and then significantly improve. Some of these "ALS reversals" even make a complete recovery back to normal neurological function. The investigator has independently verified 34 of these cases so far through review of medical records and peer-reviewed literature. These patients are different in their demographics and disease characteristics as compared to patients with more typically progressive ALS. One possible explanation for these cases is that these patients are genetically different than most patients with ALS and that these differences confer a form of disease "resistance". Study of these selected reversal patients may yield valuable clues to endogenous mechanisms of ALS resistance. The concept of genetic conferred ability to resist a disease is not novel. A group of patients who could unexpectedly "control" HIV due to a mutant allele has led to an improved understanding of HIV pathophysiology and a new treatment

This is a pilot case-control study attempting to discover genetic correlates to ALS reversals. The investigator will collect demographics, disease characteristics, pedigree information and saliva samples from ALS reversals. Whole genome DNA will be extracted and sequenced from these saliva samples. The genomes of ALS reversals will then be compared with whole genome sequencing previously completed from a biorepository of de-identified samples of more typically progressive patients with ALS. The study will not save any saliva samples collected as a part of this new protocol for future research.

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke ALS Clinic / DUSOM Dept of Neurology / DUHS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Participants will be enrolled by invitation only. Potential participants will have had a previously verified diagnosis of ALS or PMA and a verified sustained and robust reversal of disease.

Description

Inclusion Criteria:

1. Prior participation in Documentation of Known ALS Reversals (Duke IRB Pro00076395)
2. Confirmation of ALS or PMA (primary muscular atrophy) diagnosis through medical record review (previously documented in Documentation of Known ALS Reversals protocol)
3. Sustained, robust improvement on at least one objective ALS outcomes measure (ex. ALSFRS-R, FVC, strength testing, EMG) (previously documented in Documentation of Known ALS Reversals protocol)
4. Able to understand English

Exclusion Criteria:

1. History of cognitive impairment severe enough to preclude informed consent, reported by patient on direct questioning or as suspected by research personnel from Documentation of Known ALS Reversals (Duke IRB Pro00076395) study data
2. Prior participation in the Phenotype Genotype and Biomarkers in ALS and Related Disorders (RDCRN #8001) protocol

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
genetic comparison	comparison of genes of participants with ALS reversals to genes of more typically progressive patients with ALS	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
factors associated with genes	further genetic analysis for any interaction of demographics, rate of disease progression, or disease characteristics	1 day

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: CReATe Consortium (funded by NIH/NCATS/NINDS)
• Investigators: Study Chair: Richard S Bedlack, MD, PhD, Duke Health

Publications and helpful links

General Publications

• ALSUntangled Group. ALSUntangled No. 12: Dean Kraft, Energy Healer. Amyotroph Lateral Scler. 2011 Sep;12(5):389-91. doi: 10.3109/17482968.2011.609309. No abstract available.
• Bedlack RS, Vaughan T, Wicks P, Heywood J, Sinani E, Selsov R, Macklin EA, Schoenfeld D, Cudkowicz M, Sherman A. How common are ALS plateaus and reversals? Neurology. 2016 Mar 1;86(9):808-12. doi: 10.1212/WNL.0000000000002251. Epub 2015 Dec 9.
• http://www.wsj.com/articles/the-mystery-of-als-patients-who-see-improvement-1465845332
• Ozdinler PH, Silverman RB. Treatment of amyotrophic lateral sclerosis: lessons learned from many failures. ACS Med Chem Lett. 2014 Oct 8;5(11):1179-81. doi: 10.1021/ml500404b. eCollection 2014 Nov 13.
• Harrison D and Bedlack R (unpublished data).
• Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996 Aug 22;382(6593):722-5. doi: 10.1038/382722a0.

Helpful Links

• public website advertising the Study of ALS Reversals Program (St.A.R.) and the Replication of ALS Reversals (R.O.A.R.) Program
• public website with reviews of alternative and off-label treatments with the goal of helping people with ALS make more informed decisions about them

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2018
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: March 8, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (Actual): March 14, 2018

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: amyotrophic lateral sclerosis; motor neuron disease; progressive muscular atrophy; whole genome sequencing; ALS reversals
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal
• Other Study ID Numbers: Pro00091570; 8007 (Registry Identifier: Rare Disease Clinical Research Network)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information obtained from this analysis (genotypic data), as well as information about disease signs and symptoms (phenotypic data), will be entered into one or more scientific repositories maintained by organizations such as the New York Genome Center (NYGC) and the Federal Government. One such repository is the Database of Genotypes and Phenotypes (dbGaP), a data repository at the NIH. All data and information will be submitted via a secure transmission process to a high security network within NIH.

While the information and data resulting from this study may be presented at scientific meetings or published in a scientific journal, your name or other personal information will not be revealed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No