Amyotrophic Lateral SclerosisNCT01925196
Natural History and Biomarkers of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Caused by the C9ORF72 Gene Mutation
An observational study of Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Some people have a mutation in the C9ORF72 gene that causes amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). The mutation causes a small piece of DNA to repeat itself thousands of times. The C9ORF gene mutation mostly occurs in families. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, Frontotemporal Lobar Degeneration
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2013to 23 Feb 2021
- Phase
- Observational
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: Participants with C9ORF72 mutation
Who may be able to join
- Patients will be included if they:
- Are age 18 or older
- Have a confirmed repeat expansion in the C9ORF72 gene
Who cannot join
- Patients will be excluded if they
- have other major neurological or medical diseases that may cause progressive weakness or cognitive dysfunction, such as structural brain or spinal cord disease, metabolic diseases, paraneoplastic syndromes, hereditary diseases, infectious diseases, peripheral neuropathy or radiculopathy or other significant neurological abnormalities.
- require daytime ventilator support at the time of study entry
- are unable to travel to NIH at the time of study entry
- are unwilling to have follow-up visits
- are unable to understand or decline to sign the Informed Consent at the time of study entry. Participants can remain in the study (with DPA consent and participant assent) if they lose consent capacity.
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- have pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, or shrapnel fragments, metal fragments in the eye) that exclude magnetic resonance imaging
- have unstable medical conditions that, in the opinion of the investigators, prevent safe participation in this study.
- are participating in experimental treatment trials at the time of study entry or plan such participation within 6 months of entry.
- Patients will not be excluded if they are receiving standard care medications for treatment of ALS and its symptoms, or are participating in non-treatment clinical research studies. Patients will be permitted to participate in experimental treatment trials after the 6 month follow-up visit.
- Patients with pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, or shrapnel fragments, metal fragments in the eye) will not be excluded but will not undergo magnetic resonance imaging or transcranial magnetic stimulation.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Natural History and Biomarkers of C9ORF72 Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Background:
- Some people have a mutation in the C9ORF72 gene that causes amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). The mutation causes a small piece of DNA to repeat itself thousands of times. The C9ORF gene mutation mostly occurs in families. In those families, some persons have ALS and others have FTD. Occasionally the C9ORF gene mutation occurs in persons without a family history. Researchers want to understand how this gene causes different diseases. They will study how symptoms caused by the C9ORF gene develop and change over time. They will measure symptoms that occur in ALS and in FTD. In particular, they will measure strength, ability to move, thinking, and memory. They will also see if other tests are associated with progression of disease. These tests, called biomarkers, may help detect or measure C9ORF72 disease in the future.
Read more
Objectives:
- To understand how symptoms change over time in people with mutations in a gene called C9ORF72, which causes ALS and FTD.
Eligibility:
- Adults over age 18 who have this genetic mutation
Design:
- Participants will have up to 4 in-person visits and 3 telephone interviews over 3 years. Each in-person visit may take place over several days. They may be either inpatient or outpatient visits.
- At each visit, participants will undergo a series of brain, language, and behavior tests. These will include:
- Magnetic resonance imaging (MRI) of the brain. This uses magnets, radio waves, and computers to produce detailed pictures of the brain.
- Collecting spinal fluid. The clinician will make the participant s back numb and then insert a needle to collect fluid.
<TAB>- Blood samples will be taken.
<TAB>- Participants will be asked to perform several language and movement tests.
<TAB>- Small skin samples will be taken on one visit
- Between visits, participants will answer questions about their health over the phone 3 times.
Read the detailed description
Objective
The primary objective of this study is to characterize the natural history of disease in patients who carry a repeat expansion in the C9ORF72 gene, which causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The secondary objective is to assess whether candidate biomarkers correlate with disease progression.
Study population
62 persons with a documented repeat expansion in C9ORF72 gene who have ALS, ALS-FTD, or FTD or who are carriers of the gene mutation and have a symptomatic family member.
Design
Participants will undergo a structured battery of clinical and neuropsychological tests at enrollment and at three follow-up visits to NIH to assess disease severity. During these visits, physiological, imaging, blood, and CSF for testing of candidate biomarkers will be obtained. Between visits to NIH, assessments of functional status and cognition will be carried out by phone. Participants may be seen earlier than the scheduled follow-up visit or at home if phone assessments indicate clinical deterioration.
Outcome measures
There will be three primary outcome measures, for changes in three areas of function over the first six months. The primary measure of the severity of motor clinical function will be the ALS Functional rating scale-revised (ALSFRS-R). The primary measure of the severity of cognitive function will be changes in verbal fluency score. The primary measure of the severity of behavioral dysfunction will be the caregiver assessment of the fronto-behavioral index (FBI). Secondary clinical outcomes will be the forced vital capacity (FVC) and survival. The correlation between primary and secondary clinical outcome measures and candidate biomarkers measures will be analyzed in an exploratory fashion to determine whether candidate biomarkers are predictive of disease onset or progression.
- Keywords
- Motor Neuron Disease, Frontotemporal Dementia, Cognitive Testing, Magnetic Resonance Imaging (MRI), Transcranial Magnetic Stimulation (TMS), Natural History
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Frontotemporal Lobar Degeneration, Motor Neuron Disease, Frontotemporal Dementia
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 |
|---|---|---|
| C9ORF72 | Participants with C9ORF72 mutation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Verbal Fluency Score
measure of the severity of cognitive function
Measured: baseline and every 6 months therafter for 3 years
Fronto behavioral Index (FBI)
measure of the severity of behavioral dysfunction
Measured: baseline and every 6 months thereafter for 6 years
ALS Functional Rating Scale Revised
measure of the severity of motor clinical function
Measured: baseline and every 6 months therafter for 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2013 (estimated)
- Study start30 Sep 2013
- Primary completion23 Feb 2021
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 Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Justin Y Kwan, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01925196
- Sponsor's protocol ID
- 130188
- Other IDs
- 13-N-0188
- Status last verified
- 17 Aug 2026
- First submitted
- 15 Aug 2013
- Last updated
- 22 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Krishnan G, Raitcheva D, Bartlett D, Prudencio M, McKenna-Yasek DM, Douthwright C, Oskarsson BE, Ladha S, King OD, Barmada SJ, Miller TM, Bowser R, Watts JK, Petrucelli L, Brown RH, Kankel MW, Gao FB. Poly(GR) and poly(GA) in cerebrospinal fluid as potential biomarkers for C9ORF72-ALS/FTD. Nat Commun. 2022 May 19;13(1):2799. doi: 10.1038/s41467-022-30387-4.
PubMed 35589711