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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02372773
Other study ID # 14-007532
Secondary ID U01AG045390
Status Completed
Phase
First received
Last updated
Start date April 2015
Est. completion date June 30, 2020

Study information

Verified date July 2020
Source Mayo Clinic
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 398
Est. completion date June 30, 2020
Est. primary completion date June 30, 2020
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 90 Years
Eligibility Inclusion Criteria:

1. Must be a member of family with a known mutation in one of the three major FTLD related genes: MAPT, PGRN, or C9ORF72.

2. At least 18 years of age.

3. 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)

4. Have a reliable informant who personally speaks with or sees that subject at least weekly.

5. Subject is sufficiently fluent in English to complete all measures

6. Subject must be willing and able to consent to the protocol and undergo yearly evaluations over 3 years.

7. Subject must be willing and able to undergo neuropsychological testing (at least at baseline visit).

8. Subject must have no contraindication to MRI imaging.

Exclusion Criteria

1. Known presence of a structural brain lesion (e.g. tumor, cortical infarct).

2. Presence of another neurologic disorder which could impact findings (eg, multiple sclerosis).

3. Subject is unwilling to return for follow-up yearly, undergo neuropsychological testing and MR imaging.

4. Subject has no reliable informant.

Study Design


Locations

Country Name City State
Canada University of British Columbia Vancouver British Columbia
United States Harvard University Charlestown Massachusetts
United States Mayo Clinic Florida Jacksonville Florida
United States Columbia University New York New York
United States Univerisity of Pennsylvania Philadelphia Pennsylvania
United States Mayo Clinic Rochester Minnesota
United States Washington University Saint Louis Missouri
United States University of California, San Francisco, Memory and Aging Center, Department of Neurology San Francisco California

Sponsors (3)

Lead Sponsor Collaborator
Mayo Clinic National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (24)

Boeve B, Bove J, Brannelly P, Brushaber D, Coppola G, Dever R, Dheel C, Dickerson B, Dickinson S, Faber K, Fields J, Fong J, Foroud T, Forsberg L, Gavrilova R, Gearhart D, Ghoshal N, Goldman J, Graff-Radford J, Graff-Radford N, Grossman M, Haley D, Heuer — View Citation

Boeve BF, Rosen HJ. Multimodal imaging in familial FTLD: phenoconversion and planning for the future. Brain. 2019 Jan 1;142(1):8-11. doi: 10.1093/brain/awy314. — View Citation

Boxer AL, Gold M, Feldman H, Boeve BF, Dickinson SL, Fillit H, Ho C, Paul R, Pearlman R, Sutherland M, Verma A, Arneric SP, Alexander BM, Dickerson BC, Dorsey ER, Grossman M, Huey ED, Irizarry MC, Marks WJ, Masellis M, McFarland F, Niehoff D, Onyike CU, P — View Citation

Casaletto KB, Staffaroni AM, Wolf A, Appleby B, Brushaber D, Coppola G, Dickerson B, Domoto-Reilly K, Elahi FM, Fields J, Fong JC, Forsberg L, Ghoshal N, Graff-Radford N, Grossman M, Heuer HW, Hsiung GY, Huey ED, Irwin D, Kantarci K, Kaufer D, Kerwin D, K — View Citation

Chen Q, Boeve BF, Schwarz CG, Reid R, Tosakulwong N, Lesnick TG, Bove J, Brannelly P, Brushaber D, Coppola G, Dheel C, Dickerson BC, Dickinson S, Faber K, Fields J, Fong J, Foroud T, Forsberg L, Gavrilova RH, Gearhart D, Ghoshal N, Goldman J, Graff-Radfor — View Citation

Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick T, Brushaber D, Dheel C, Fields J, Forsberg L, Gavrilova R, Gearhart D, Graff-Radford J, Graff-Radford N, Jack CR Jr, Jones D, Knopman D, Kremers WK, Lapid M, Rademakers R, Ramos EM, Syrjanen J, Boxer AL, — View Citation

Chen Q, Boeve BF, Senjem M, Tosakulwong N, Lesnick TG, Brushaber D, Dheel C, Fields J, Forsberg L, Gavrilova R, Gearhart D, Graff-Radford J, Graff-Radford NR, Jack CR Jr, Jones DT, Knopman DS, Kremers WK, Lapid M, Rademakers R, Syrjanen J, Boxer AL, Rosen — View Citation

Chen Q, Boeve BF, Tosakulwong N, Lesnick T, Brushaber D, Dheel C, Fields J, Forsberg L, Gavrilova R, Gearhart D, Haley D, Gunter JL, Graff-Radford J, Jones D, Knopman D, Graff-Radford N, Kraft R, Lapid M, Rademakers R, Syrjanen J, Wszolek ZK, Rosen H, Box — View Citation

Chen Q, Boeve BF, Tosakulwong N, Lesnick T, Brushaber D, Dheel C, Fields J, Forsberg L, Gavrilova R, Gearhart D, Haley D, Gunter JL, Graff-Radford J, Jones D, Knopman D, Graff-Radford N, Kraft R, Lapid M, Rademakers R, Wszolek ZK, Rosen H, Boxer AL, Kanta — View Citation

Gentry MT, Lapid MI, Syrjanen J, Calvert K, Hughes S, Brushaber D, Kremers W, Bove J, Brannelly P, Coppola G, Dheel C, Dickerson B, Dickinson S, Faber K, Fields J, Fong J, Foroud T, Forsberg L, Gavrilova R, Gearhart D, Ghoshal N, Goldman J, Graff-Radford — View Citation

Heuer HW, Wang P, Rascovsky K, Wolf A, Appleby B, Bove J, Bordelon Y, Brannelly P, Brushaber DE, Caso C, Coppola G, Dickerson B, Dickinson S, Domoto-Reilly K, Faber K, Ferrall J, Fields J, Fishman A, Fong J, Foroud T, Forsberg LK, Gearhart D, Ghazanfari B — View Citation

Kornak J, Fields J, Kremers W, Farmer S, Heuer HW, Forsberg L, Brushaber D, Rindels A, Dodge H, Weintraub S, Besser L, Appleby B, Bordelon Y, Bove J, Brannelly P, Caso C, Coppola G, Dever R, Dheel C, Dickerson B, Dickinson S, Dominguez S, Domoto-Reilly K, — View Citation

Miyagawa T, Brushaber D, Syrjanen J, Kremers W, Fields J, Forsberg LK, Heuer HW, Knopman D, Kornak J, Boxer A, Rosen H, Boeve B; ARTFL/LEFFTDS Consortium. Use of the CDR® plus NACC FTLD in mild FTLD: Data from the ARTFL/LEFFTDS consortium. Alzheimers Deme — View Citation

Miyagawa T, Brushaber D, Syrjanen J, Kremers W, Fields J, Forsberg LK, Heuer HW, Knopman D, Kornak J, Boxer A, Rosen HJ, Boeve BF, Appleby B, Bordelon Y, Bove J, Brannelly P, Caso C, Coppola G, Dever R, Dheel C, Dickerson B, Dickinson S, Dominguez S, Domo — View Citation

Moore KM, Nicholas J, Grossman M, McMillan CT, Irwin DJ, Massimo L, Van Deerlin VM, Warren JD, Fox NC, Rossor MN, Mead S, Bocchetta M, Boeve BF, Knopman DS, Graff-Radford NR, Forsberg LK, Rademakers R, Wszolek ZK, van Swieten JC, Jiskoot LC, Meeter LH, Do — View Citation

Olney NT, Ong E, Goh SM, Bajorek L, Dever R, Staffaroni AM, Cobigo Y, Bock M, Chiang K, Ljubenkov P, Kornak J, Heuer HW, Wang P, Rascovsky K, Wolf A, Appleby B, Bove J, Bordelon Y, Brannelly P, Brushaber D, Caso C, Coppola G, Dickerson BC, Dickinson S, Do — View Citation

Pottier C, Ren Y, Perkerson RB 3rd, Baker M, Jenkins GD, van Blitterswijk M, DeJesus-Hernandez M, van Rooij JGJ, Murray ME, Christopher E, McDonnell SK, Fogarty Z, Batzler A, Tian S, Vicente CT, Matchett B, Karydas AM, Hsiung GR, Seelaar H, Mol MO, Finger — View Citation

Ramos EM, Dokuru DR, Van Berlo V, Wojta K, Wang Q, Huang AY, Deverasetty S, Qin Y, van Blitterswijk M, Jackson J, Appleby B, Bordelon Y, Brannelly P, Brushaber DE, Dickerson B, Dickinson S, Domoto-Reilly K, Faber K, Fields J, Fong J, Foroud T, Forsberg LK — View Citation

Rosen HJ, Boeve BF, Boxer AL. Tracking disease progression in familial and sporadic frontotemporal lobar degeneration: Recent findings from ARTFL and LEFFTDS. Alzheimers Dement. 2020 Jan;16(1):71-78. doi: 10.1002/alz.12004. Review. — View Citation

Staffaroni AM, Bajorek L, Casaletto KB, Cobigo Y, Goh SM, Wolf A, Heuer HW, Elahi FM, Ljubenkov PA, Dever R, Kornak J, Appleby B, Bove J, Bordelon Y, Brannelly P, Brushaber D, Caso C, Coppola G, Dheel C, Dickerson BC, Dickinson S, Dominguez S, Domoto-Reil — View Citation

Staffaroni AM, Cobigo Y, Goh SM, Kornak J, Bajorek L, Chiang K, Appleby B, Bove J, Bordelon Y, Brannelly P, Brushaber D, Caso C, Coppola G, Dever R, Dheel C, Dickerson BC, Dickinson S, Dominguez S, Domoto-Reilly K, Faber K, Ferrall J, Fields JA, Fishman A — View Citation

Staffaroni AM, Ljubenkov PA, Kornak J, Cobigo Y, Datta S, Marx G, Walters SM, Chiang K, Olney N, Elahi FM, Knopman DS, Dickerson BC, Boeve BF, Gorno-Tempini ML, Spina S, Grinberg LT, Seeley WW, Miller BL, Kramer JH, Boxer AL, Rosen HJ. Longitudinal multim — View Citation

Thijssen EH, La Joie R, Wolf A, Strom A, Wang P, Iaccarino L, Bourakova V, Cobigo Y, Heuer H, Spina S, VandeVrede L, Chai X, Proctor NK, Airey DC, Shcherbinin S, Duggan Evans C, Sims JR, Zetterberg H, Blennow K, Karydas AM, Teunissen CE, Kramer JH, Grinbe — View Citation

Toller G, Ranasinghe K, Cobigo Y, Staffaroni A, Appleby B, Brushaber D, Coppola G, Dickerson B, Domoto-Reilly K, Fields J, Fong J, Forsberg L, Ghoshal N, Graff-Radford N, Grossman M, Heuer H, Hsiung GY, Huey E, Irwin D, Kantarci K, Kaufer D, Kerwin D, Kno — View Citation

* Note: There are 24 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 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 neuropsychological, clinical/behavioral, neuroimaging measures 5 years
Secondary 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 neuropsychological, clinical/behavioral, neuroimaging measures 5 years
Secondary Value of novel imaging and clinical measures for characterizing asymptomatic familial FTD subjects, and factors predicting clinical rates of progression in each group. neuropsychological, clinical/behavioral, neuroimaging measures 5 years
Secondary Genetic and biofluid factors that modify rates of clinical and neuroimaging decline in the asymptomatic and symptomatic phases of familial FTD. genetic and biolfuid factors 5 years