C9ORF72 Amyotrophic Lateral Sclerosis (ALS)NCT02686268
Understanding Clinical Phenotype and Collecting Biomarker Samples in C9ORF72 ALS
An observational study of C9ORF72 Amyotrophic Lateral Sclerosis (ALS), run by Washington University School of Medicine at 8 sites in 2 countries.
Trial summary
This research study is being performed to better understand a specific form of Amyotrophic Lateral Sclerosis (ALS) caused by a mutation (or abnormality) of the C9ORF72 gene. This mutation is the most common genetic cause of ALS, and is present in 40% of ALS patients with a family history of ALS and 5-10% of ALS… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- C9ORF72 Amyotrophic Lateral Sclerosis (ALS)
- How many people
- 128 participants
- Where
- 8 sitesin 2 countries
- Study dates
- Feb 2015to 2 Oct 2018
- 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
- No healthy volunteers
- Adult, Older adult
Study population: Known positive C9ORF72 ALS status upon enrollment
Who may be able to join
- Males or females of any race aged 18 or older
- Known positive C9ORF72 ALS status via CLIA-certified lab results.
- Capable of providing informed consent and following study procedures. In the event that an individual lacks the ability to provide informed consent, informed consent may be sought from the individual's legal, surrogate representative.
- Geographically accessible to the site.
Who cannot join
- Geographically inaccessible to the site
- C9ORF72 ALS negative via CLIA-certified lab results
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States7 sites
University of Massachusetts
Amherst, Massachusetts, 01003
Johns Hopkins
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Cedars Sinai Medical Center
Los Angeles, California, 90048
Columbia University Medical Center
New York, New York, 10027
Washington University in St. Louis
St Louis, Missouri, 63110
Sentara Health Care / Sentara Neurology Specialists
Virginia Beach, Virginia, 23454
About this study
This research study is being performed to better understand a specific form of Amyotrophic Lateral Sclerosis (ALS) caused by a mutation (or abnormality) of the C9ORF72 gene. This mutation is the most common genetic cause of ALS, and is present in 40% of ALS patients with a family history of ALS and 5-10% of ALS patients without a family history of ALS.
Read the detailed description
Individuals diagnosed with ALS, who are confirmed to carry the Chromosome 9 Open Reading Frame 72 (C9ORF72) gene mutation by CLIA-certified lab results, are eligible for enrollment. Researchers want to understand the natural history of C9ORF72 related ALS in terms of measures of rate of progression as well as understanding how the size of the hexanucleotide repeat expansion influences disease parameters. The investigators hope that the intense study of patients with the C9ORF72 mutation will ultimately help us develop treatments for this common form of ALS.
Objectives:
- Enroll a total of 120 C9ORF72 ALS participants with known mutation at the time of enrollment.
- Determine the C9ORF72 hexanucleotide repeat expansion size in all subjects
- Define ALS disease course
- Determine to what degree the disease course correlates with expansion size
- Collect biomarker samples (blood, DNA and CSF)
Eligibility:
- Adults over age 18 with known C9ORF72 ALS status
Design:
Participants will have up to 9 in-person visits (this includes two Optional visits for lumbar puncture procedures) and 5 telephone interviews over 3 years. Each in-person visit may be tied to a regular clinic visit if subject is local (except for the optional lumbar puncture visits) or if the subject is from out of town one initial visit can be set up with all other visits performed via a telephone call and medical records review.
At each in town visit, subjects will undergo a blood draw (optional lumbar puncture) and two questionnaires (ALS Functional Rating Scale - revised ALSFRS-R) which measures motor function and the ALS-Cognitive Behavioral Screen (ALS-CBS) which will detect signs of Frontal Temporal Dementia and a breathing test to determine Slow Vital Capacity (SVC) measurements.
For out of town subjects - blood draws can be scheduled locally and sent to the study site for analysis. The ALSFRS-R can be performed over the phone along with other study related questions.
The C9ORF72 mutation is called a "dominant" mutation, which means that their children have a 50% chance of inheriting the gene. Most people who inherit the C9ORF72 mutation will develop either ALS or the related disease called fronto-temporal dementia. However, it may be possible for someone to test positive for the C9ORF72 gene mutation and never develop symptoms. Furthermore, in addition to C9ORF72, there are many other gene mutations that can cause ALS. This study will not test these other genes, and therefore a negative test result for the C9ORF72 mutation will not exclude the possibility that you have a heritable form of ALS.
In order to understand the natural history of C9ORF72 related ALS in terms of measures of rate of progression, the investigators need to understand how the size of the hexanucleotide repeat expansion influences disease parameters. A C9ORF72-focused clinical trial defining an accurate historical control population, will be critical since there may not be enough subjects for a placebo controlled trial. To be ready for upcoming therapeutic trials, the investigators need to start the detailed characterization of the C9ORF72 patients immediately.
- Keywords
- Amyotrophic Lateral Sclerosis, ALS, C9ORF72 gene mutation, Chromosome 9 open reading frame 72 protein, Natural history, Biomarkers, Amyotrophic Lateral Sclerosis, Familial, Amyotrophic Lateral Sclerosis, Sporadic, Frontotemporal Dementia-Amyotrophic Lateral Sclerosis
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Amyotrophic lateral sclerosis 1, Frontotemporal Dementia With Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Individuals diagnosed with known positive C9ORF72 ALS | Individuals diagnosed with known positive C9ORF72 ALS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Collection of clinical data and biomarker samples
The primary outcome measures will be the collection of clinical data (ALSFRS, ALS-CBS and SVC) to determine rates of disease progression and collection of biomarkers samples (blood, CSF) to be correlated with the clinical measures.
Measured: December 2017
Secondary outcomes (1)
Correlation of repeat expansion size with clinical outcome measures and determination of C9ORF72 patients eligibility for clinical trials
The secondary outcome measures include determination of the C9ORF72 hexanucleotide repeat expansion size and correlating this with the outcome measures of disease progression collected (ALSFRS-R/month, decrease in SVC/month and ALS Cognitive Screen) and determination of C9ORF72 ALS patients that may be available for a clinical trial.
Measured: December 2017
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2016 (estimated)
- Study startFeb 2015
- Primary completion31 Dec 2017
- Study completion2 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for C9ORF72 Amyotrophic Lateral Sclerosis (ALS)Studies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 only
- Time perspective
- Prospective
- Enrolment
- 128 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Cedars-Sinai Medical Center, UMC Utrecht, Johns Hopkins University, Massachusetts General Hospital, University of Massachusetts, Amherst, Biogen, ALS Association, Columbia University
- Responsible party
- Principal investigator, Timothy M. Miller, MD, PhD, Washington University School of Medicine
- Investigators
- Timothy M Miller, MD, PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02686268
- Sponsor's protocol ID
- 14LGCA123
- Status last verified
- Jul 2021
- First submitted
- 11 Feb 2016
- Last updated
- 8 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: The study design has a robust plan to share de-identified data (but personally identifiable data will not be shared). When study information is shared, it will be "de-identified", meaning that the study will remove all personal identifiers so that all collected data and samples are stored under a unique subject ID study code ("coded"). In other words, the study has been designed to keep personal details separate from all samples and study information. The results of this trial will be published in peer-reviewed journals. No personal identifiers will be included.
Publications
Cammack AJ, Atassi N, Hyman T, van den Berg LH, Harms M, Baloh RH, Brown RH, van Es MA, Veldink JH, de Vries BS, Rothstein JD, Drain C, Jockel-Balsarotti J, Malcolm A, Boodram S, Salter A, Wightman N, Yu H, Sherman AV, Esparza TJ, McKenna-Yasek D, Owegi MA, Douthwright C; Alzheimer's Disease Neuroimaging Initiative; McCampbell A, Ferguson T, Cruchaga C, Cudkowicz M, Miller TM. Prospective natural history study of C9orf72 ALS clinical characteristics and biomarkers. Neurology. 2019 Oct 22;93(17):e1605-e1617. doi: 10.1212/WNL.0000000000008359. Epub 2019 Oct 2.
PubMed 31578300
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding Clinical Phenotype and Collecting Biomarker Samples in C9ORF72 ALS
- ClinicalTrials.gov ID
- NCT02686268
- Acronym / sponsor ID
- 14LGCA123
- Keywords
- Amyotrophic Lateral Sclerosis, ALS, C9ORF72 gene mutation, Chromosome 9 open reading frame 72 protein, Natural history, Biomarkers, Amyotrophic Lateral Sclerosis, Familial, Amyotrophic Lateral Sclerosis, Sporadic
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 128 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Cedars-Sinai Medical Center, UMC Utrecht, Johns Hopkins University, Massachusetts General Hospital, University of Massachusetts, Amherst, Biogen, ALS Association, Columbia University
- Study start
- Feb 2015
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 2 Oct 2018 (actual)
- First posted
- 19 Feb 2016 (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.
This research study is being performed to better understand a specific form of Amyotrophic Lateral Sclerosis (ALS) caused by a mutation (or abnormality) of the C9ORF72 gene. This mutation is the most common genetic cause of ALS, and is present in 40% of ALS patients with a family history of ALS and 5-10% of ALS patients without a family history of ALS.
Detailed description
Individuals diagnosed with ALS, who are confirmed to carry the Chromosome 9 Open Reading Frame 72 (C9ORF72) gene mutation by CLIA-certified lab results, are eligible for enrollment. Researchers want to understand the natural history of C9ORF72 related ALS in terms of measures of rate of progression as well as understanding how the size of the hexanucleotide repeat expansion influences disease parameters. The investigators hope that the intense study of patients with the C9ORF72 mutation will ultimately help us develop treatments for this common form of ALS.
Objectives:
- Enroll a total of 120 C9ORF72 ALS participants with known mutation at the time of enrollment.
- Determine the C9ORF72 hexanucleotide repeat expansion size in all subjects
- Define ALS disease course
- Determine to what degree the disease course correlates with expansion size
- Collect biomarker samples (blood, DNA and CSF)
Eligibility:
- Adults over age 18 with known C9ORF72 ALS status
Design:
Participants will have up to 9 in-person visits (this includes two Optional visits for lumbar puncture procedures) and 5 telephone interviews over 3 years. Each in-person visit may be tied to a regular clinic visit if subject is local (except for the optional lumbar puncture visits) or if the subject is from out of town one initial visit can be set up with all other visits performed via a telephone call and medical records review.
At each in town visit, subjects will undergo a blood draw (optional lumbar puncture) and two questionnaires (ALS Functional Rating Scale - revised ALSFRS-R) which measures motor function and the ALS-Cognitive Behavioral Screen (ALS-CBS) which will detect signs of Frontal Temporal Dementia and a breathing test to determine Slow Vital Capacity (SVC) measurements.
For out of town subjects - blood draws can be scheduled locally and sent to the study site for analysis. The ALSFRS-R can be performed over the phone along with other study related questions.
The C9ORF72 mutation is called a "dominant" mutation, which means that their children have a 50% chance of inheriting the gene. Most people who inherit the C9ORF72 mutation will develop either ALS or the related disease called fronto-temporal dementia. However, it may be possible for someone to test positive for the C9ORF72 gene mutation and never develop symptoms. Furthermore, in addition to C9ORF72, there are many other gene mutations that can cause ALS. This study will not test these other genes, and therefore a negative test result for the C9ORF72 mutation will not exclude the possibility that you have a heritable form of ALS.
In order to understand the natural history of C9ORF72 related ALS in terms of measures of rate of progression, the investigators need to understand how the size of the hexanucleotide repeat expansion influences disease parameters. A C9ORF72-focused clinical trial defining an accurate historical control population, will be critical since there may not be enough subjects for a placebo controlled trial. To be ready for upcoming therapeutic trials, the investigators need to start the detailed characterization of the C9ORF72 patients immediately.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Individuals diagnosed with known positive C9ORF72 ALS | – | –Individuals diagnosed with known positive C9ORF72 ALS |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Known positive C9ORF72 ALS status upon enrollment
Key inclusion criteria (4 listed)
- Males or females of any race aged 18 or older
- Known positive C9ORF72 ALS status via CLIA-certified lab results.
- Capable of providing informed consent and following study procedures. In the event that an individual lacks the ability to provide informed consent, informed consent may be sought from the individual's legal, surrogate representative.
- Geographically accessible to the site.
Key exclusion criteria (2 listed)
- Geographically inaccessible to the site
- C9ORF72 ALS negative via CLIA-certified lab results
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
Collection of clinical data and biomarker samples
Time frame: December 2017
The primary outcome measures will be the collection of clinical data (ALSFRS, ALS-CBS and SVC) to determine rates of disease progression and collection of biomarkers samples (blood, CSF) to be correlated with the clinical measures.
1 secondary outcome
Correlation of repeat expansion size with clinical outcome measures and determination of C9ORF72 patients eligibility for clinical trials
Time frame: December 2017
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 8 Jul 2021.
- Background: PubMed 31578300Cammack AJ, Atassi N, Hyman T, van den Berg LH, Harms M, Baloh RH, Brown RH, van Es MA, Veldink JH, de Vries BS, Rothstein JD, Drain C, Jockel-Balsarotti J, Malcolm A, Boodram S, Salter A, Wightman N, Yu H, Sherman AV, Esparza TJ, McKenna-Yasek D, Owegi MA, Douthwright C; Alzheimer's Disease Neuroimaging Initiative; McCampbell A, Ferguson T, Cruchaga C, Cudkowicz M, Miller TM. Prospective natural history study of C9orf72 ALS clinical characteristics and biomarkers. Neurology. 2019 Oct 22;93(17):e1605-e1617. doi: 10.1212/WNL.0000000000008359. Epub 2019 Oct 2.
- Individual participant dataSharing planned: No. The study design has a robust plan to share de-identified data (but personally identifiable data will not be shared). When study information is shared, it will be "de-identified", meaning that the study will remove all personal identifiers so that all collected data and samples are stored under a unique subject ID study code ("coded"). In other words, the study has been designed to keep personal details separate from all samples and study information. The results of this trial will be published in peer-reviewed journals. No personal identifiers will be included.
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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.
Timothy M Miller, MD, PhD principal investigator
Washington University School of Medicine
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of C9ORF72 Amyotrophic Lateral Sclerosis (ALS), run by Washington University School of Medicine at 8 sites in 2 countries.
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 8 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Netherlands. 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?
Collection of clinical data and biomarker samples (time frame: December 2017). 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 NCT02686268, which also lists 1 linked publication.
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 8 Jul 2021.