Investigating Complex Neurodegenerative Disorders Related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Background:

Neurodegenerative disorders can lead to problems in movement or memory. Some can cause abnormal proteins to build up in brain cells. Researchers want to understand whether these diseases have related causes or risk factors.

Objective:

To test people with movement or thinking and memory problems to see if they are eligible for research studies.

Eligibility:

People ages 18 and older with a neurodegenerative disorder associated with accumulation of TDP-43 or Tau proteins

Design:

Participants will have a screening visit. This may take place over 2-3 days. Tests include:

Medical history

Physical exam

Questions about behavior and mood

Tests of memory, attention, concentration, and thinking

Movement measurement. The speed at which participants can stand up from a chair, tap their finger and foot, and walk a short distance will be measured. Some movements will be videotaped. They will be videotaped while they speak and read a paragraph.

Blood tests. This might include genetic testing.

Lung and breathing tests

MRI. They will lie on a table that slides into a cylinder that takes pictures of the body. Some participants will get a dye through IV.

Electromyography. A thin needle will be inserted into the muscles to measure electrical signals.

Nerve tests. Small electrodes on the skin record muscle and nerve activity.

A small piece of skin may be removed.

A skin or blood sample may be taken to create stem cells.

Optional lumbar puncture. A needle will be inserted into the space between the bones of the back to collect fluid.

If participants are not eligible for current studies, they may be contacted in the future.

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis; Frontotemporal Dementia; Progressive Supranuclear Palsy

Detailed Description

Objectives

The primary objective is to evaluate patients referred with a diagnosis of frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or related adult-onset neurodegenerative disorders to assess patient eligibility for ongoing protocols. The secondary objective is to develop and maintain a registry of characterized patients and presymptopmatic carriers of gene mutations that cause ALS-FTD spectrum disorders. The exploratory objectives are to obtain biospecimens from clinically characterized patients to carry out laboratory-based studies aimed at understanding the molecular pathways and genetic overlap between these neurodegenerative disorders and to perform 7 tesla magnetic resonance imaging studies to identify imaging biomarkers of neurodegeneration.

Study population

Adults referred with clinical diagnoses of frontotemporal dementia, motor neuron disorder, or related adult-onset neurodegenerative disorder. Presymptomatic carriers of genes known to cause familial FTD or ALS

Design

All participants will undergo clinical tests to confirm diagnoses and to stage disease severity, including a standard battery of tests to measure cognitive and motor functions. Participants may opt-in for research procedures such as phlebotomy, skin biopsy, leukapheresis, and lumbar puncture to obtain biospecimens for laboratory research, and magnetic resonance imaging or transcranial magnetic stimulation may be used to explore biomarkers of disease.

Outcome measures

Clinical information will be analyzed as part of our research to identify common features and differences among participants.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Carol H Hoffman; Phone Number: (301) 451-1229; Email: carol.hoffman@nih.gov
• Study Contact Backup: Name: Justin Y Kwan, M.D.; Phone Number: (301) 496-7428; Email: justin.kwan@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY8664111010 800-411-1222; Email: prpl@cc.nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults with a diagnosis of ALS, FTD, or a related adult-onset neurodegenerative disorder

Description

• INCLUSION CRITERIA:

Patients will be included if they

• Are age 18 or older
• Have been given a diagnosis by a neurologist of frontotemporal dementia, primary progressive aphasia, semantic dementia, motor neuron disorder, amyotrophic lateral sclerosis, progressive bulbar palsy, corticobasal neurodegenerative disorder OR
• Carry a mutation in a gene that causes familial ALS or FTD

EXCLUSION CRITERIA:

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, infectious diseases, peripheral neuropathy or radiculopathy or other significant neurological abnormalities.
• Have an unstable medical condition that, in the opinion of the investigators, makes participation unsafe
• Require daytime ventilator support at the time of study entry
• Are unable to travel to NIH
• 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.
• Patients with tattoos above the neck or permanent make up will be excluded from undergoing 7T MRI.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients; patients who are referred with a diagnosis of frontotemporal dementia, motor neuron disorder, or related adult-onset neurodegenerative disorder to assess patient eligibility for ongoing protocols

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical information	Clinical information will be analyzed as part of our research to identify common features and differences among participants.	10/30/2025

Collaborators and Investigators

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Justin Y Kwan, M.D., National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

General Publications

• Snowden JS, Adams J, Harris J, Thompson JC, Rollinson S, Richardson A, Jones M, Neary D, Mann DM, Pickering-Brown S. Distinct clinical and pathological phenotypes in frontotemporal dementia associated with MAPT, PGRN and C9orf72 mutations. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(7-8):497-505. doi: 10.3109/21678421.2015.1074700. Epub 2015 Oct 16.
• Renton AE, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs JR, Schymick JC, Laaksovirta H, van Swieten JC, Myllykangas L, Kalimo H, Paetau A, Abramzon Y, Remes AM, Kaganovich A, Scholz SW, Duckworth J, Ding J, Harmer DW, Hernandez DG, Johnson JO, Mok K, Ryten M, Trabzuni D, Guerreiro RJ, Orrell RW, Neal J, Murray A, Pearson J, Jansen IE, Sondervan D, Seelaar H, Blake D, Young K, Halliwell N, Callister JB, Toulson G, Richardson A, Gerhard A, Snowden J, Mann D, Neary D, Nalls MA, Peuralinna T, Jansson L, Isoviita VM, Kaivorinne AL, Holtta-Vuori M, Ikonen E, Sulkava R, Benatar M, Wuu J, Chio A, Restagno G, Borghero G, Sabatelli M; ITALSGEN Consortium; Heckerman D, Rogaeva E, Zinman L, Rothstein JD, Sendtner M, Drepper C, Eichler EE, Alkan C, Abdullaev Z, Pack SD, Dutra A, Pak E, Hardy J, Singleton A, Williams NM, Heutink P, Pickering-Brown S, Morris HR, Tienari PJ, Traynor BJ. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. 2011 Oct 20;72(2):257-68. doi: 10.1016/j.neuron.2011.09.010. Epub 2011 Sep 21.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2017
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): October 30, 2025

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: July 20, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 7, 2024

More Information

Terms related to this study

• Keywords: Motor Neuron Disease; Natural History; Progressive Supranuclear Palsy; Frontotemporal Dementia; TDP-43; Corticobasal Syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neuromuscular Diseases; Basal Ganglia Diseases; Movement Disorders; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Tauopathies; Cranial Nerve Diseases; Ocular Motility Disorders; Language Disorders; Communication Disorders; Paralysis; Speech Disorders; Frontotemporal Lobar Degeneration; Ophthalmoplegia; Aphasia; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Dementia; Neurodegenerative Diseases; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Supranuclear Palsy, Progressive
• Other Study ID Numbers: 170131; 17-N-0131

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: .Undecided.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No