Study of ALS Reversals 4: LifeTime Exposures (StARLiTE)

Hypothesis: There exists patients who have met ALS or PMA diagnostic criteria and subsequently experienced robust and sustained improvement, i.e. a "reversal." Thirty-eight of these patients were identified in the prior Duke University study, Documentation of Known ALS Reversals (St.A.R. Protocol 1, Duke IRB Pro00076395). The investigators hypothesize these patients have had different environmental exposures than patients with typically progressive ALS. Identification of specific environmental influences may point to exposures which are protective or exposure that lead to the development of a rare and novel reversible ALS-like disease.

Objective: This study seeks to identify environmental exposures associated with ALS reversals.

Study Overview

• Status: Completed
• Conditions: Motor Neuron 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 investigators have independently verified 38 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 have had protective environmental exposures. Another possible explanation is that these patients have had unique environmental exposures that led to a reversible form of ALS. Study of these selected reversal patients may yield valuable clues to environmental mechanisms of ALS resistance.

This is a pilot case-control study attempting to discover environmental exposure correlates to ALS reversals. The investigators will recruit and enroll ALS reversal "cases" to fill out an online survey form about their life. Topics include demographics, employment history, military service, substance use, physical activity, family medical history, disease progression, residential history, occupational exposures, home exposures, hobby exposures, hormonal and reproductive history (female identifying subjects only), caffeine, head and neck injuries, electrical shocks, health insurance, subjective perception of the etiology of ALS, and clinical features of disease. "Control" participant data will come from a pre-existing database.

• Study Type: Observational
• Enrollment (Actual): 25

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: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited from the cohort of subjects (38 to-date) who participated in the Documentation of Known ALS Reversals (Duke IRB Pro00076395) protocol and were subsequently thought to have an ALS Reversal.

Description

Inclusion Criteria:

• Prior participation in Documentation of Known ALS Reversals (Duke IRB Pro00076395)
• Confirmation of ALS or PMA (primary muscular atrophy) diagnosis through medical record review (previously documented in Documentation of Known ALS Reversals protocol)
• 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)
• Able to understand English

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ALS and PMA Reversals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Life Time Environmental Exposures	Case-control analysis of differences in environmental exposures over life time of subject. Environmental exposures will be measured with the National ALS Registry survey. Cases are "ALS Reversals." Controls are typically progressive patients with ALS.	2 hours to fill out survey

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Centers for Disease Control and Prevention; National ALS Registry; Agency for Toxic Substances and Disease Registry

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
• Harrison D, Mehta P, van Es MA, Stommel E, Drory VE, Nefussy B, van den Berg LH, Crayle J, Bedlack R; Pooled Resource Open-Access ALS Clinical Trials Consortium. "ALS reversals": demographics, disease characteristics, treatments, and co-morbidities. Amyotroph Lateral Scler Frontotemporal Degener. 2018 Nov;19(7-8):495-499. doi: 10.1080/21678421.2018.1457059. Epub 2018 Apr 2.
• Crayle J and Bedlack R. Unpublished data. 2018.

Helpful Links

• published manuscript

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2018
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: October 11, 2018
• First Posted (Actual): October 16, 2018

Study Record Updates

• Last Update Posted (Actual): January 20, 2023
• Last Update Submitted That Met QC Criteria: January 18, 2023
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: amyotrophic lateral sclerosis; motor neuron disease; progressive muscular atrophy; ALS Reversal; PMA Reversal
• 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: Pro00100219

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No