Natural History and Biomarkers of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Caused by the C9ORF72 Gene Mutation

NCT01925196 | Completed

• 2 other identifiers: 13018813-N-0188
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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.

Conditions

Amyotrophic Lateral Sclerosis; Frontotemporal Lobar Degeneration

Keywords

Motor Neuron Disease; Frontotemporal Dementia; Cognitive Testing; Magnetic Resonance Imaging (MRI); Transcranial Magnetic Stimulation (TMS); Natural History

Outcome Measures

Primary Outcomes (3)

• Verbal Fluency Score

  measure of the severity of cognitive function

  baseline and every 6 months therafter for 3 years

• Fronto behavioral Index (FBI)

  measure of the severity of behavioral dysfunction

  baseline and every 6 months thereafter for 6 years

• ALS Functional Rating Scale Revised

  measure of the severity of motor clinical function

  baseline and every 6 months therafter for 3 years

Study Arms (1)

C9ORF72

Participants with C9ORF72 mutation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants with C9ORF72 mutation

You may qualify if:

• Patients will be included if they:
• Are age 18 or older
• Have a confirmed repeat expansion in the C9ORF72 gene

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 35589711 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Frontotemporal Lobar Degeneration; Motor Neuron Disease; Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Dementia; Brain Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Justin Y Kwan, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2013
• First Posted: August 19, 2013
• Study Start: September 30, 2013
• Primary Completion: February 23, 2021
• Last Updated: May 5, 2026

Record last verified: 2026-02-06

Locations

US (1)