Study of ALS Reversals 2: Genetic Analyses

Amyotrophic Lateral Sclerosis Clinical Trial

— StAR2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03464903
• Other study ID #: Pro00091570
• Secondary ID: 8007
• Status: Completed
• Start date: June 22, 2018
• Est. completion date: December 1, 2023

Study information

• Verified date: January 2024
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: December 1, 2023
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Atrophy
• Motor Neuron Disease
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Progressive Muscular Atrophy
• Sclerosis

Locations

Country	Name	City	State
United States	Duke ALS Clinic / DUSOM Dept of Neurology / DUHS	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	CReATe Consortium (funded by NIH/NCATS/NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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. — View Citation

Harrison D and Bedlack R (unpublished data).

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	genetic comparison	comparison of genes of participants with ALS reversals to genes of more typically progressive patients with ALS	1 day
Secondary	factors associated with genes	further genetic analysis for any interaction of demographics, rate of disease progression, or disease characteristics	1 day

External 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