Study of ALS Reversals 2: Genetic Analyses (StAR2)

• ClinicalTrials.gov Identifier: NCT03464903
• Recruitment Status: Active, not recruiting
• First Posted: March 14, 2018
• Last Update Posted: December 21, 2022
• Sponsor: Duke University
• Collaborator: CReATe Consortium (funded by NIH/NCATS/NINDS)
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

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.

Condition or disease
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 Design

• Study Type: Observational [Patient Registry]
• Actual Enrollment: 26 participants
• Observational Model: Case-Control
• Time Perspective: Other
• Target Follow-Up Duration: 1 Day
• Official Title: ALS Reversals: Genetic Analyses (St.A.R. Protocol 2) RDCRN CReATe Protocol #8007
• Actual Study Start Date: June 22, 2018
• Estimated Primary Completion Date: August 1, 2025
• Estimated Study Completion Date: August 1, 2025

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. genetic comparison [ Time Frame: 1 day ]
   comparison of genes of participants with ALS reversals to genes of more typically progressive patients with ALS

Secondary Outcome Measures :

1. factors associated with genes [ Time Frame: 1 day ]
   further genetic analysis for any interaction of demographics, rate of disease progression, or disease characteristics

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• 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.

Criteria

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

Contacts and Locations

Locations

United States, North Carolina

Duke ALS Clinic / DUSOM Dept of Neurology / DUHS

Durham, North Carolina, United States, 27705

Sponsors and Collaborators

Duke University

CReATe Consortium (funded by NIH/NCATS/NINDS)

Investigators

• Study Chair: Richard S Bedlack, MD, PhD; Duke Health

More Information

Additional Information:

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 

Publications:

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.

http://www.wsj.com/articles/the-mystery-of-als-patients-who-see-improvement-1465845332

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.

Harrison D and Bedlack R (unpublished data).

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.

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.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03464903
• Other Study ID Numbers: Pro00091570; 8007 ( Registry Identifier: Rare Disease Clinical Research Network )
• First Posted: March 14, 2018
• Last Update Posted: December 21, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Duke University:

amyotrophic lateral sclerosis; progressive muscular atrophy; motor neuron disease; ALS reversals; whole genome sequencing

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Muscular Atrophy; Muscular Atrophy, Spinal; Sclerosis; Atrophy; Pathologic Processes; Pathological Conditions, Anatomical; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Neuromuscular Manifestations; Neurologic Manifestations