Amyotrophic Lateral Sclerosis (ALS)ALSNCT00821132
Genetics of Familial and Sporadic ALS
An observational study of Amyotrophic Lateral Sclerosis (ALS) and Familial Amyotrophic Lateral Sclerosis, run by Northwestern University at 1 site in United States.
Trial summary
We are collecting blood samples, clinical and family information from ALS (amyotrophic lateral sclerosis) patients and their families to identify causes of ALS and ALS/dementia. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Amyotrophic Lateral Sclerosis (ALS), Familial Amyotrophic Lateral Sclerosis, ALS With Frontotemporal Dementia (ALS/FTD)
- What is being tested?
- Genetic study of ALS families
- How many people
- 13,521 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1991to Jan 2023
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Open to all ALS patients and selected family members
Who may be able to join
- Patients with Amyotrophic Lateral Sclerosis or ALS and frontotemporal dementia
- Selected family members, generally brothers and sisters of an ALS patient, the patient's parents
Who cannot join
- Under 18 years old
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
About this study
Official title: Identification of Genes Causing Familial ALS or Increasing Risk for Sporadic ALS and ALS With Frontotemporal Dementia and Understanding Disease Mechanism.
We are collecting blood samples, clinical and family information from ALS (amyotrophic lateral sclerosis) patients and their families to identify causes of ALS and ALS/dementia.
Read the detailed description
The investigators' long term goals are to improve diagnosis and develop effective treatments that arrest or ameliorate symptoms of ALS, and possibly delay or prevent disease onset in individuals at risk for developing familial ALS (FALS). In order to do this one must understand how disease develops at a molecular level. Identification of genes that increase risk for developing all types of ALS will reveal the pathways of molecular events that are involved in ALS.
The investigators are collecting blood samples, family and medical histories of patients with all types of ALS, (familial and sporadic, with and without frontotemporal dementia, and primary lateral sclerosis and particular family members. Samples are coded to maintain confidentiality. Travel is not necessary.
As well as seeking to identify new genes implicated in ALS, the investigators continue our study of families with known genetic mutations to more fully characterize that disease mechanism.
Linkage analysis and affected relative pair analysis will be used to identify causative FALS genes and disequilibrium analysis and association studies are being done for sporadic ALS.
Results from these studies will provide insight into the underlying disease mechanisms of ALS and provide targets for therapeutic interventions.
- Conditions
- Amyotrophic Lateral Sclerosis (ALS), Familial Amyotrophic Lateral Sclerosis, ALS With Frontotemporal Dementia (ALS/FTD), Lou Gehrig's Disease, Motor Neuron Disease (MND), Primary Lateral Sclerosis (PLS)
- Being tested
- Genetic study of ALS families
- Keywords
- FALS, ALS, ALS/FTD, SALS, MND, PLS
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic study of ALS familiesOther
Also called familial ALS, sporadic ALS, genetics of ALS, ALS with frontotemporal dementia
Collection and analysis of genetic material, medical and family histories from families with ALS
| Study group | Role | What they receive |
|---|---|---|
| ALS families | Patients with either inherited or sporadic ALS or PLS and selected family members Receives: Other: Genetic study of ALS families |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of genes that increase risk for sporadic ALS or cause inherited ALS.
Study of each identified gene will help us understand the molecular events that produce different types of ALS. This will aid in identification of markers that may be associated with each type which will assist with diagnosis and may provide targets for rational therapy.
Measured: Dec 2025
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2009 (estimated)
- Study startJan 1991
- Primary completionJan 2023
- Study completionJan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (62)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral Sclerosis (ALS)Studies of the same condition, open and under way.
- More trials run by Northwestern 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
- Family based
- Time perspective
- Other
- Enrolment
- 13,521 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Teepu Siddique, Northwestern University
- Investigators
- Teepu Siddique, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00821132
- Sponsor's protocol ID
- Lab01
- Other IDs
- RO1N505641-04
- Acronym
- ALS
- Status last verified
- Jan 2023
- First submitted
- 9 Jan 2009
- Last updated
- 26 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Pytte J, Anderton RS, Flynn LL, Theunissen F, Jiang L, Pitout I, James I, Mastaglia FL, Saunders AM, Bedlack R, Siddique T, Siddique N, Akkari PA. Association of a structural variant within the SQSTM1 gene with amyotrophic lateral sclerosis. Neurol Genet. 2020 Feb 27;6(2):e406. doi: 10.1212/NXG.0000000000000406. eCollection 2020 Apr.
PubMed 32185242Deng HX, Zhai H, Shi Y, Liu G, Lowry J, Liu B, Ryan EB, Yan J, Yang Y, Zhang N, Yang Z, Liu E, Ma YC, Siddique T. Efficacy and long-term safety of CRISPR/Cas9 genome editing in the SOD1-linked mouse models of ALS. Commun Biol. 2021 Mar 25;4(1):396. doi: 10.1038/s42003-021-01942-4.
PubMed 33767386Ryan EB, Yan J, Miller N, Dayanidhi S, Ma YC, Deng HX, Siddique T. Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology. iScience. 2021 Jan 18;24(2):102061. doi: 10.1016/j.isci.2021.102061. eCollection 2021 Feb 19.
PubMed 33659869Ryan EB, Deng HX. Does Somatic Mosaicism Account for Some Sporadic ALS? Neurol Genet. 2021 Jan 12;7(1):e555. doi: 10.1212/NXG.0000000000000555. eCollection 2021 Feb. No abstract available.
PubMed 33977141Lowry JL, Ryan EB, Esengul YT, Siddique N, Siddique T. Intricacies of aetiology in intrafamilial degenerative disease. Brain Commun. 2020 Oct 6;2(2):fcaa120. doi: 10.1093/braincomms/fcaa120. eCollection 2020.
PubMed 33134917Ortega JA, Daley EL, Kour S, Samani M, Tellez L, Smith HS, Hall EA, Esengul YT, Tsai YH, Gendron TF, Donnelly CJ, Siddique T, Savas JN, Pandey UB, Kiskinis E. Nucleocytoplasmic Proteomic Analysis Uncovers eRF1 and Nonsense-Mediated Decay as Modifiers of ALS/FTD C9orf72 Toxicity. Neuron. 2020 Apr 8;106(1):90-107.e13. doi: 10.1016/j.neuron.2020.01.020. Epub 2020 Feb 13.
PubMed 32059759Wu JJ, Cai A, Greenslade JE, Higgins NR, Fan C, Le NTT, Tatman M, Whiteley AM, Prado MA, Dieriks BV, Curtis MA, Shaw CE, Siddique T, Faull RLM, Scotter EL, Finley D, Monteiro MJ. ALS/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function. Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15230-15241. doi: 10.1073/pnas.1917371117. Epub 2020 Jun 8.
PubMed 32513711Silani V, Corcia P, Harms MB, Rouleau G, Siddique T, Ticozzi N. Genetics of primary lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2020 Nov;21(sup1):28-34. doi: 10.1080/21678421.2020.1837177.
PubMed 33602012Edens BM, Yan J, Miller N, Deng HX, Siddique T, Ma YC. A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis. Elife. 2017 May 2;6:e25453. doi: 10.7554/eLife.25453.
PubMed 28463112Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng HX, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993 Mar 4;362(6415):59-62. doi: 10.1038/362059a0.
PubMed 8446170Chen W, Saeed M, Mao H, Siddique N, Dellefave L, Hung WY, Deng HX, Sufit RL, Heller SL, Haines JL, Pericak-Vance M, Siddique T. Lack of association of VEGF promoter polymorphisms with sporadic ALS. Neurology. 2006 Aug 8;67(3):508-10. doi: 10.1212/01.wnl.0000227926.42370.04.
PubMed 16894118Li YJ, Pericak-Vance MA, Haines JL, Siddique N, McKenna-Yasek D, Hung WY, Sapp P, Allen CI, Chen W, Hosler B, Saunders AM, Dellefave LM, Brown RH, Siddique T. Apolipoprotein E is associated with age at onset of amyotrophic lateral sclerosis. Neurogenetics. 2004 Dec;5(4):209-13. doi: 10.1007/s10048-004-0193-0. Epub 2004 Oct 2.
PubMed 15657798Yang Y, Hentati A, Deng HX, Dabbagh O, Sasaki T, Hirano M, Hung WY, Ouahchi K, Yan J, Azim AC, Cole N, Gascon G, Yagmour A, Ben-Hamida M, Pericak-Vance M, Hentati F, Siddique T. The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet. 2001 Oct;29(2):160-5. doi: 10.1038/ng1001-160.
PubMed 11586297Hentati A, Ouahchi K, Pericak-Vance MA, Nijhawan D, Ahmad A, Yang Y, Rimmler J, Hung W, Schlotter B, Ahmed A, Ben Hamida M, Hentati F, Siddique T. Linkage of a commoner form of recessive amyotrophic lateral sclerosis to chromosome 15q15-q22 markers. Neurogenetics. 1998 Dec;2(1):55-60. doi: 10.1007/s100480050052.
PubMed 9933301Ajroud-Driss S, Saeed M, Khan H, Siddique N, Hung WY, Sufit R, Heller S, Armstrong J, Casey P, Siddique T, Lukas TJ. Riluzole metabolism and CYP1A1/2 polymorphisms in patients with ALS. Amyotroph Lateral Scler. 2007 Oct;8(5):305-9. doi: 10.1080/17482960701500650.
PubMed 17852022
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Genes Causing Familial ALS or Increasing Risk for Sporadic ALS and ALS With Frontotemporal Dementia and Understanding Disease Mechanism.
- ClinicalTrials.gov ID
- NCT00821132
- Acronym / sponsor ID
- ALS / Lab01
- Conditions
- Amyotrophic Lateral Sclerosis (ALS), Familial Amyotrophic Lateral Sclerosis, ALS With Frontotemporal Dementia (ALS/FTD), Lou Gehrig's Disease, Motor Neuron Disease (MND), Primary Lateral Sclerosis (PLS)
- Keywords
- FALS, ALS, ALS/FTD, SALS, MND, PLS
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 13,521 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Jan 1991 (actual)
- Primary completion
- Jan 2023 (actual)
- Study completion
- Jan 2023 (actual)
- First posted
- 13 Jan 2009 (estimated)
- 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.
We are collecting blood samples, clinical and family information from ALS (amyotrophic lateral sclerosis) patients and their families to identify causes of ALS and ALS/dementia.
Detailed description
The investigators' long term goals are to improve diagnosis and develop effective treatments that arrest or ameliorate symptoms of ALS, and possibly delay or prevent disease onset in individuals at risk for developing familial ALS (FALS). In order to do this one must understand how disease develops at a molecular level. Identification of genes that increase risk for developing all types of ALS will reveal the pathways of molecular events that are involved in ALS.
The investigators are collecting blood samples, family and medical histories of patients with all types of ALS, (familial and sporadic, with and without frontotemporal dementia, and primary lateral sclerosis and particular family members. Samples are coded to maintain confidentiality. Travel is not necessary.
As well as seeking to identify new genes implicated in ALS, the investigators continue our study of families with known genetic mutations to more fully characterize that disease mechanism.
Linkage analysis and affected relative pair analysis will be used to identify causative FALS genes and disequilibrium analysis and association studies are being done for sporadic ALS.
Results from these studies will provide insight into the underlying disease mechanisms of ALS and provide targets for therapeutic interventions.
Study design
- Observational model
- Family based
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ALS families | – | Other: Genetic study of ALS familiesPatients with either inherited or sporadic ALS or PLS and selected family members |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Open to all ALS patients and selected family members
Key inclusion criteria (2 listed)
- Patients with Amyotrophic Lateral Sclerosis or ALS and frontotemporal dementia
- Selected family members, generally brothers and sisters of an ALS patient, the patient's parents
Key exclusion criteria (1 listed)
- Under 18 years old
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genetic study of ALS familiesAlso: familial ALS, sporadic ALS, genetics of ALS, ALS with frontotemporal dementiaCollection and analysis of genetic material, medical and family histories from families with ALS | Other | ALS families |
Primary outcome
Identification of genes that increase risk for sporadic ALS or cause inherited ALS.
Time frame: Dec 2025
Study of each identified gene will help us understand the molecular events that produce different types of ALS. This will aid in identification of markers that may be associated with each type which will assist with diagnosis and may provide targets for rational therapy.
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 26 Jan 2023.
- Background: PubMed 32185242Pytte J, Anderton RS, Flynn LL, Theunissen F, Jiang L, Pitout I, James I, Mastaglia FL, Saunders AM, Bedlack R, Siddique T, Siddique N, Akkari PA. Association of a structural variant within the SQSTM1 gene with amyotrophic lateral sclerosis. Neurol Genet. 2020 Feb 27;6(2):e406. doi: 10.1212/NXG.0000000000000406. eCollection 2020 Apr.
- Background: PubMed 33767386Deng HX, Zhai H, Shi Y, Liu G, Lowry J, Liu B, Ryan EB, Yan J, Yang Y, Zhang N, Yang Z, Liu E, Ma YC, Siddique T. Efficacy and long-term safety of CRISPR/Cas9 genome editing in the SOD1-linked mouse models of ALS. Commun Biol. 2021 Mar 25;4(1):396. doi: 10.1038/s42003-021-01942-4.
- Background: PubMed 33659869Ryan EB, Yan J, Miller N, Dayanidhi S, Ma YC, Deng HX, Siddique T. Early death of ALS-linked CHCHD10-R15L transgenic mice with central nervous system, skeletal muscle, and cardiac pathology. iScience. 2021 Jan 18;24(2):102061. doi: 10.1016/j.isci.2021.102061. eCollection 2021 Feb 19.
- Background: PubMed 33977141Ryan EB, Deng HX. Does Somatic Mosaicism Account for Some Sporadic ALS? Neurol Genet. 2021 Jan 12;7(1):e555. doi: 10.1212/NXG.0000000000000555. eCollection 2021 Feb. No abstract available.
- Background: PubMed 33134917Lowry JL, Ryan EB, Esengul YT, Siddique N, Siddique T. Intricacies of aetiology in intrafamilial degenerative disease. Brain Commun. 2020 Oct 6;2(2):fcaa120. doi: 10.1093/braincomms/fcaa120. eCollection 2020.
- Background: PubMed 32059759Ortega JA, Daley EL, Kour S, Samani M, Tellez L, Smith HS, Hall EA, Esengul YT, Tsai YH, Gendron TF, Donnelly CJ, Siddique T, Savas JN, Pandey UB, Kiskinis E. Nucleocytoplasmic Proteomic Analysis Uncovers eRF1 and Nonsense-Mediated Decay as Modifiers of ALS/FTD C9orf72 Toxicity. Neuron. 2020 Apr 8;106(1):90-107.e13. doi: 10.1016/j.neuron.2020.01.020. Epub 2020 Feb 13.
- Background: PubMed 32513711Wu JJ, Cai A, Greenslade JE, Higgins NR, Fan C, Le NTT, Tatman M, Whiteley AM, Prado MA, Dieriks BV, Curtis MA, Shaw CE, Siddique T, Faull RLM, Scotter EL, Finley D, Monteiro MJ. ALS/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function. Proc Natl Acad Sci U S A. 2020 Jun 30;117(26):15230-15241. doi: 10.1073/pnas.1917371117. Epub 2020 Jun 8.
- Background: PubMed 33602012Silani V, Corcia P, Harms MB, Rouleau G, Siddique T, Ticozzi N. Genetics of primary lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2020 Nov;21(sup1):28-34. doi: 10.1080/21678421.2020.1837177.
- Background: PubMed 28463112Edens BM, Yan J, Miller N, Deng HX, Siddique T, Ma YC. A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis. Elife. 2017 May 2;6:e25453. doi: 10.7554/eLife.25453.
- Results publication: PubMed 8446170Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O'Regan JP, Deng HX, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993 Mar 4;362(6415):59-62. doi: 10.1038/362059a0.
- Results publication: PubMed 16894118Chen W, Saeed M, Mao H, Siddique N, Dellefave L, Hung WY, Deng HX, Sufit RL, Heller SL, Haines JL, Pericak-Vance M, Siddique T. Lack of association of VEGF promoter polymorphisms with sporadic ALS. Neurology. 2006 Aug 8;67(3):508-10. doi: 10.1212/01.wnl.0000227926.42370.04.
- Results publication: PubMed 15657798Li YJ, Pericak-Vance MA, Haines JL, Siddique N, McKenna-Yasek D, Hung WY, Sapp P, Allen CI, Chen W, Hosler B, Saunders AM, Dellefave LM, Brown RH, Siddique T. Apolipoprotein E is associated with age at onset of amyotrophic lateral sclerosis. Neurogenetics. 2004 Dec;5(4):209-13. doi: 10.1007/s10048-004-0193-0. Epub 2004 Oct 2.
- Individual participant dataSharing planned: No
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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.
Teepu Siddique, MD principal investigator
Northwestern University
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 (ALS) and Familial Amyotrophic Lateral Sclerosis, run by Northwestern 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 2 inclusion and 1 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 26 Jan 2023. 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?
Identification of genes that increase risk for sporadic ALS or cause inherited ALS. (time frame: Dec 2025). 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 NCT00821132, which also lists 62 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 26 Jan 2023.