Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects - Full Text View

Purpose

This study is being done to learn more about normal thinking and behavior, mild thinking and behavior problems, Frontotemporal Dementia and other forms of dementia in families in which one or more relatives have a mutation associated with Frontotemporal Dementia.

Condition
Familial Frontotemporal Dementia


Study Type:	Observational
Study Design:	Observational Model: Family-Based Time Perspective: Prospective
Official Title:	Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects

Resource links provided by NLM:

Genetics Home Reference related topics: CHMP2B-related frontotemporal dementia GRN-related frontotemporal dementia frontotemporal dementia with parkinsonism-17 inclusion body myopathy with early-onset Paget disease and frontotemporal dementia

MedlinePlus related topics: Dementia

Genetic and Rare Diseases Information Center resources: Pick's Disease Frontotemporal Dementia Frontotemporal Dementia, Ubiquitin-positive Primary Progressive Aphasia Semantic Dementia

U.S. FDA Resources

Further study details as provided by Bradley Boeve, Mayo Clinic:

Primary Outcome Measures:

Rate of decline in traditional measures of clinical (neuropsychological and behavioral composites) function and cortical volume on structural MRI in the symptomatic phase of familial FTD [ Time Frame: 5 years ]

Secondary Outcome Measures:

Rate of decline in traditional measures of clinical (neuropsychological and behavioral composites) function and cortical volume on structural MRI in the asymptomatic phase of familial FTD [ Time Frame: 5 years ]
Value of novel imaging and clinical measures for characterizing asymptomatic familial FTD subjects, and factors predicting clinical rates of progression in each group. [ Time Frame: 5 years ]
Genetic and biofluid factors that modify rates of clinical and neuroimaging decline in the asymptomatic and symptomatic phases of familial FTD. [ Time Frame: 5 years ]

Biospecimen Retention: Samples With DNA

Blood - DNA, Plasma, Serum, Peripheral blood mononuclear cells, RNA, Cerebrospinal Fluid


Estimated Enrollment:	300
Study Start Date:	April 2015
Estimated Study Completion Date:	April 2019
Estimated Primary Completion Date:	April 2019 (Final data collection date for primary outcome measure)

Groups/Cohorts
Frontotemporal Dementia - MAPT Frontotemporal Dementia with microtubule associated protein tau (MAPT) mutation
Frontotemporal Dementia - PGRN Frontotemporal Dementia with progranulin (PGRN; also known as granulin or GRN) mutation
Frontotemporal Dementia - C9OR72 Frontotemporal Dementia with chromosome 9 open reading frame 72 (C9ORF72) mutation.
Control Member of family with a known mutation in one of the three major FTD related genes: MAPT, PGRN, and C9ORF72.

Detailed Description:

This multicenter study will enroll 300 members of familial Frontotemporal Dementia (FTD) families across 8 experienced FTD research centers with a known mutation in MAPT, PGRN, or C9ORF72 (100 mutation carriers with mild dementia or minimally symptomatic yet non-demented, 100 asymptomatic mutation carriers, and 100 clinically normal relatives who are non-mutation carriers) to obtain annual assessments including T1-MRI, FLAIR, diffusion tensor imaging (DTI), ASL perfusion (ASLp), intrinsic connectivity functional MRI (icfMRI), MR spectroscopy (MRS), CSF, blood, and behavioral, neuropsychological and functional assessment, for a total of three assessments per participant.

A primary goal of this study is to identify the most robust and reliable methods to track disease progression in familial FTD so that disease-modifying therapeutic trials can be designed appropriately.

Eligibility


Ages Eligible for Study:	18 Years to 90 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Have a mutation, or be a relative of an individual with a mutation, in one of the three most common genes associated with Frontotemporal Dementia - microtubule associated protein tau (MAPT), progranulin (PGRN; also known as granulin or GRN), or chromosome 9 open reading frame 72 (C9ORF72).

Criteria

Inclusion Criteria:

Must be a member of family with a known mutation in one of the three major FTLD related genes: MAPT, PGRN, or C9ORF72.
At least 18 years of age.
The predominant phenotype in the kindred must be cognitive/behavioral (ie, kindreds in whom parkinsonism or ALS is the predominant clinical phenotype among affected relatives may be excluded)
Have a reliable informant who personally speaks with or sees that subject at least weekly.
Subject is sufficiently fluent in English to complete all measures
Subject must be willing and able to consent to the protocol and undergo yearly evaluations over 3 years.
Subject must be willing and able to undergo neuropsychological testing (at least at baseline visit).
Subject must have no contraindication to MRI imaging.

Exclusion Criteria

Known presence of a structural brain lesion (e.g. tumor, cortical infarct).
Presence of another neurologic disorder which could impact findings (eg, multiple sclerosis).
Subject is unwilling to return for follow-up yearly, undergo neuropsychological testing and MR imaging.
Subject has no reliable informant.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02372773

Contacts


Contact: Christina Dheel	507-293-5551	dheel.christina@mayo.edu
Contact: Josie Williams	507-293-5354	williams.josie@mayo.edu

Locations


United States, California
University of California, San Francisco, Memory and Aging Center, Department of Neurology	Recruiting
San Francisco, California, United States, 94358
Contact: Reilly Dever 415-476-0670 reilly.dever@ucsf.edu
Principal Investigator: Howard Rosen, MD
United States, Florida
Mayo Clinic Florida	Recruiting
Jacksonville, Florida, United States, 32224
Contact: Dana Haley 904-953-9680 Haley.Dana@mayo.edu
Principal Investigator: Neill Graff-Radford, MD
United States, Massachusetts
Harvard University	Recruiting
Charlestown, Massachusetts, United States, 02129
Contact: Samantha Krivensky 617-726-6205 skrivensky@mgh.harvard.edu
Principal Investigator: Bradford Dickerson, MD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Christina Dheel 507-293-5551 dheel.christina@mayo.edu
Contact RSTLEFFTDSMANAGEMENT@mayo.edu
Principal Investigator: Bradley Boeve, MD
United States, Missouri
Washington University	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Lynne Jones 314-362-8420 jonesly@wustl.edu
Principal Investigator: Nupur Ghoshal, MD, PhD
United States, New York
Columbia University	Recruiting
New York, New York, United States, 10032
Contact: Masood Manoochehri mm2626@cumc.columbia.edu
Principal Investigator: Edward Huey, MD
United States, Pennsylvania
Univerisity of Pennsylvania	Recruiting
Phildelphia, Pennsylvania, United States, 19104
Contact: Christina Ray 215-349-5873 rayc@mail.med.upenn.edu
Principal Investigator: Murray Gossman, MD
Canada, British Columbia
University of British Columbia	Recruiting
Vancouver, British Columbia, Canada, V6T 2B5
Contact: Pheth Sengdy 604 822 7989 Pheth.Sengdy@vch.ca
Principal Investigator: Ging-Yeuk Hsiung, MD
Principal Investigator: Ian Mackenzie, MD

Sponsors and Collaborators

Mayo Clinic

National Institute on Aging (NIA)

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators


Principal Investigator:	Bradley Boeve, MD	Mayo Clinic
Principal Investigator:	Howard Rosen, MD	University of California, San Francisco

More Information


Responsible Party:	Bradley Boeve, Professor of Neurology, Mayo Clinic
ClinicalTrials.gov Identifier:	NCT02372773 History of Changes
Other Study ID Numbers:	14-007532 U01AG045390 ( U.S. NIH Grant/Contract )
Study First Received:	February 20, 2015
Last Updated:	March 21, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	De-identified data can be shared following a formal request and approval by the executive committee overseeing the protocol.

Keywords provided by Bradley Boeve, Mayo Clinic:


Frontotemporal Dementia MAPT PGRN C9ORF72

Additional relevant MeSH terms:


Dementia Frontotemporal Dementia Aphasia, Primary Progressive Pick Disease of the Brain Brain Diseases Central Nervous System Diseases Nervous System Diseases Neurocognitive Disorders Mental Disorders Frontotemporal Lobar Degeneration TDP-43 Proteinopathies	Neurodegenerative Diseases Proteostasis Deficiencies Metabolic Diseases Aphasia Speech Disorders Language Disorders Communication Disorders Neurobehavioral Manifestations Neurologic Manifestations Signs and Symptoms

ClinicalTrials.gov processed this record on July 17, 2017

Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS)