Amyotrophic Lateral SclerosisStAR2NCT03464903
Study of ALS Reversals 2: Genetic Analyses
An observational study of Amyotrophic Lateral Sclerosis and Progressive Muscular Atrophy, run by Duke University at 1 site in United States.
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… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, Progressive Muscular Atrophy
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jun 2018to 1 Dec 2023
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
- Prior participation in the Phenotype Genotype and Biomarkers in ALS and Related Disorders (RDCRN #8001) protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke ALS Clinic / DUSOM Dept of Neurology / DUHS
Durham, North Carolina, 27705
About this study
Official title: 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.
Read the 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.
- Keywords
- amyotrophic lateral sclerosis, progressive muscular atrophy, motor neuron disease, ALS reversals, whole genome sequencing
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Muscular Atrophy, Spinal, Motor Neuron Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
genetic comparison
comparison of genes of participants with ALS reversals to genes of more typically progressive patients with ALS
Measured: 1 day
Secondary outcomes (1)
factors associated with genes
further genetic analysis for any interaction of demographics, rate of disease progression, or disease characteristics
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start22 Jun 2018
- Primary completion1 Dec 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 26 participants (actual)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- CReATe Consortium (funded by NIH/NCATS/NINDS)
- Responsible party
- Sponsor
- Investigators
- Richard S Bedlack, MD, PhD, Study chair, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03464903
- Sponsor's protocol ID
- Pro00091570
- Other IDs
- 8007
- Acronym
- StAR2
- Status last verified
- Jan 2024
- First submitted
- 8 Mar 2018
- Last updated
- 11 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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.
PubMed 25408825http://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.
PubMed 21981685Harrison 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.
PubMed 26658909Samson 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.
PubMed 8751444Crayle JI, Rampersaud E, Myers JR, Wuu J, Taylor JP, Wu G, Benatar M, Bedlack RS. Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype. Neurology. 2024 Aug 27;103(4):e209696. doi: 10.1212/WNL.0000000000209696. Epub 2024 Jul 30.
PubMed 39079071
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ALS Reversals: Genetic Analyses (St.A.R. Protocol 2) RDCRN CReATe Protocol #8007
- ClinicalTrials.gov ID
- NCT03464903
- Acronym / sponsor ID
- StAR2 / Pro00091570
- Keywords
- amyotrophic lateral sclerosis, progressive muscular atrophy, motor neuron disease, ALS reversals, whole genome sequencing
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- CReATe Consortium (funded by NIH/NCATS/NINDS)
- Study start
- 22 Jun 2018 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 14 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Case-control
- Time perspective
- Other
- Target follow-up
- 1 Day
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- 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
- Prior participation in the Phenotype Genotype and Biomarkers in ALS and Related Disorders (RDCRN #8001) protocol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
genetic comparison
Time frame: 1 day
comparison of genes of participants with ALS reversals to genes of more typically progressive patients with ALS
1 secondary outcome
factors associated with genes
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2024.
- Background: PubMed 25408825Ozdinler 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.
- Backgroundhttp://www.wsj.com/articles/the-mystery-of-als-patients-who-see-improvement-1465845332
- Background: PubMed 21981685ALSUntangled 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.
- BackgroundHarrison D and Bedlack R (unpublished data).
- Background: PubMed 26658909Bedlack 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.
- Background: PubMed 8751444Samson 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.
- Derived from this study: PubMed 39079071Crayle JI, Rampersaud E, Myers JR, Wuu J, Taylor JP, Wu G, Benatar M, Bedlack RS. Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype. Neurology. 2024 Aug 27;103(4):e209696. doi: 10.1212/WNL.0000000000209696. Epub 2024 Jul 30.
- public website advertising the Study of ALS Reversals Program (St.A.R.) and the Replication of ALS Reversals (R.O.A.R.) ProgramLink provided by the sponsor.
- public website with reviews of alternative and off-label treatments with the goal of helping people with ALS make more informed decisions about themLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard S Bedlack, MD, PhD study chair
Duke Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Amyotrophic Lateral Sclerosis and Progressive Muscular Atrophy, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
genetic comparison (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03464903, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2024; AzTrials last refreshed its copy on 30 Oct 2026.