Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

Rare Diseases Clinical Research Network Advancing Research and Treatment for Frontotemporal Lobar Degeneration [ARTFL]: Research Projects 1 & 2

Sponsors

Lead Sponsor: University of California, San Francisco

Collaborator: National Center for Advancing Translational Science (NCATS)
National Institute of Neurological Disorders and Stroke (NINDS)
The Bluefield Project to Cure Frontotemporal Dementia
Tau Consortium

Source University of California, San Francisco
Brief Summary

Frontotemporal Lobar Degeneration (FTLD) is the neuropathological term for a collection of rare neurodegenerative diseases that correspond to four main overlapping clinical syndromes: frontotemporal dementia (FTD), primary progressive aphasia (PPA), corticobasal degeneration syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). The goal of this study is to build a FTLD clinical research consortium to support the development of FTLD therapies for new clinical trials. The consortium, referred to as Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL), will be headquartered at UCSF and will partner with six patient advocacy groups to manage the consortium. Participants will be evaluated at 14 clinical sites throughout North America and a genetics core will genotype all individuals for FTLD associated genes.

Detailed Description

Frontotemporal Lobar Degeneration (FTLD) is the neuropathological term for a collection of rare neurodegenerative diseases that correspond to four main overlapping clinical syndromes: frontotemporal dementia (FTD), primary progressive aphasia (PPA), corticobasal degeneration syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). The goal of this study is to build a FTLD clinical research consortium (FTLD CRC) to support the development of FTLD therapies for new clinical trials. The FTLD CRC will be headquartered at UCSF and will partner with six patient advocacy groups to manage the consortium. Patients will be evaluated at 13 clinical sites throughout North America and a genetics core will genotype all individuals for FTLD associated genes.

The study will be divided into 2 projects. The first project will be Preparing for Sporadic FTLD Clinical Trials and the second project will be a Longitudinal Assessment of Familial FTLD. Self-registration for an online registry will be available for patients and families with any FTLD syndrome. Eligible participants for research Projects 1 and 2 FTLD will be invited to a CRC site for clinical evaluations. All enrolled participants in both research projects will have a site visit consisting of a neurological exam, medical and family history, cognitive testing, and a blood draw.

Participants in Project 1 who have a diagnosis of Progressive Supranuclear Palsy Syndrome will have two additional assessments. A lumbar puncture (LP) will be performed for CSF collection, and an MRI scan of the brain will be done.

Participants in Project 2: Longitudinal Assessment of familial FTLD will return for a follow-up visit in 12 months; procedures at the follow-up visit will be identical to those at baseline. Additionally, asymptomatic participants will undergo MRI scans at both visits.

Overall Status Recruiting
Start Date September 2014
Completion Date February 2021
Primary Completion Date September 2020
Study Type Observational
Primary Outcome
Measure Time Frame
Scores of UDS FTLD Module Tests Baseline, 12 mo.
Secondary Outcome
Measure Time Frame
Progressive Supranuclear Palsy Rating Scale (PSPRS) Baseline
Neuroimaging Baseline; 12 months
Enrollment 1560
Condition
Eligibility

Sampling Method: Non-Probability Sample

Criteria:

1. Inclusion Criteria:Must meet one of the following research diagnostic criteria for a Frontotemporal lobar degeneration (FTLD) syndrome: behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), semantic variant primary progressive aphasia (svPPA), nonfluent variant primary progressive aphasia (nfvPPA), frontotemporal dementia with amyotrophic lateral sclerosis (FTD/ALS), amyotrophic lateral sclerosis alone, corticobasal syndrome (CBS), progressive supranuclear palsy (PSP) or oligosymptomatic PSP (oPSP), or have a strong family history of FTLD syndromes.

2. Between 18 and 85 (inclusive) years of age.

3. Able to walk (with assistance) at the time of enrollment.

4. Have a reliable study partner who can provide an independent evaluation of functioning.

5. Speak English or Spanish

6. Have Mini Mental State Exam (MMSE) scores between 15 - 30 (inclusive).

Exclusion Criteria:

1. Known presence of a structural brain lesion (e.g. tumor,cortical infarct) that could reasonably explain symptoms in a symptomatic participant without a known f-FTLD causing mutation.

2. Known presence of an Alzheimer's disease causing mutation in PSEN1, PSEN2 or APP; or neuropathological evidence for Alzheimer's disease as a cause of syndrome (from brain biopsy).

3. A previous history of Korsakoff encephalopathy, severe alcohol dependence (within 5 years of onset of dementia), frequent alcohol or other substance intoxication, or other neurological disorder (such as multiple sclerosis)

4. Evidence through history or laboratory testing of B12 deficiency (B12 < 95% of local laboratory's normal value), hypothyroidism (TSH >150% of normal), HIV positive,renal failure (creatinine > 2), liver failure (ALT or AST > two times normal), respiratory failure (requiring oxygen), extra-axial brain tumor (with visible compression of the brain parenchyma), large cerebral infarct that could account for clinical syndrome, large confluent white matter lesions (grades 3 or 4, [107] significant systemic medical illnesses such as deteriorating cardiovascular disease;

5. Current medication likely to affect CNS functions in the opinion of the site PI: long acting benzodiazepines such as diazepam (short-acting benzodiazepines are OK), non-SSRI antidepressants (SSRIs or trazodone are OK), no lithium, typical neuroleptics as listed in the Manual of Procedures, narcotics (codeine is OK, but hold 24 hours before neuropsychological testing), anticonvulsants (outside of therapeutic ranges), antihistamines (if taking greater than three times per week; hold 24 hours before neuropsychological testing).

6. In the site investigator's opinion, the participant cannot complete sufficient key study procedures, or equivalent assessment of impairment level.

7. For groups where MRI scans are planned procedures, any contraindication for MRI scanning, such as pacemaker or other implanted metals.

Gender: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Adam L Boxer, MD, PhD Principal Investigator Study PI
Overall Contact

Last Name: Ping Wang, MA

Phone: 415-502-7518

Email: [email protected]

Location
Facility: Status: Contact: Investigator:
University of Alabama | Birmingham, Alabama, 35294, United States Recruiting Emily McKinley, MSPH 205-996-3659 [email protected] Erik Roberson, MD Principal Investigator
University of California, Los Angeles | Los Angeles, California, 90095, United States Recruiting Miranda Maldonado [email protected] Yvette Bordelon, MD, PhD Principal Investigator
University of California, San Diego | San Diego, California, 92037, United States Recruiting Ileana Rubio [email protected] Irene Litvan, MD Principal Investigator
University of California, San Francisco | San Francisco, California, 94158, United States Recruiting Ping Wang, MA 415-502-7518 [email protected] Adam Boxer, MD, PhD Principal Investigator
Mayo Clinic - Jacksonville | Jacksonville, Florida, 32224, United States Recruiting Dana Haley 904-953-9680 [email protected] Neill Graff-Radford, M.D. Principal Investigator
Northwestern University | Chicago, Illinois, 60611, United States Recruiting Michaela Riley [email protected] Sandra Weintraub, PhD Principal Investigator
Johns Hopkins University | Baltimore, Maryland, 21287, United States Recruiting Ann Fishman 410-502-5816 [email protected] Chiadi U Onyike, MD, MHS Principal Investigator
Harvard University Massachusetts General Hospital | Charlestown, Massachusetts, 02129, United States Recruiting Erin Krahn 617-724-7092 [email protected] Bradford C Dickerson, MD Principal Investigator
Mayo Clinic - Rochester | Rochester, Minnesota, 55905, United States Recruiting Kevin Nelson 507-293-9577 [email protected] Bradley F Boeve, M.D. Principal Investigator Davis S Knopman, M.D. Principal Investigator
Washington University | Saint Louis, Missouri, 63110, United States Recruiting Tina Nolte 314-362-3839 [email protected] Nupur Ghoshal, MD, PhD Principal Investigator
Columbia University | New York, New York, 10032, United States Recruiting Masood Manoochehehri 212-305-5710 [email protected] Edward D Huey, MD Principal Investigator
University of North Carolina | Chapel Hill, North Carolina, 27599, United States Recruiting Jessica Ferrall 919-962-8852 [email protected] Daniel Kaufer, MD Principal Investigator
Case Western Reserve University Hospitals Cleveland Medical Center | Cleveland, Ohio, 44106, United States Recruiting Frances Lissemore, PhD 216-464-6203 [email protected] Brian Appleby, MD Principal Investigator
University of Pennsylvania | Philadelphia, Pennsylvania, 19104-4283, United States Recruiting Christine Ray, MSW 215-349-5873 [email protected] Murray Grossman, M.D. Principal Investigator
University of Texas Southwestern Medical Center | Dallas, Texas, 75390, United States Recruiting Jana Windsor 214-648-8543 [email protected] Diana Kerwin, MD Principal Investigator
University of Washington Harborview Medical Center | Seattle, Washington, 98104, United States Recruiting Christina Caso 206-221-9038 [email protected] Kimiko Domoto-Reilly, MD Principal Investigator
University of British Columbia | Vancouver, British Columbia, V6T 2B5, Canada Recruiting Pheth Sengdy, BSc, CCRP 604-822-7989 [email protected] Robin Hsiung, MD Principal Investigator Ian Mackenzie, MD Principal Investigator
University of Toronto | Toronto, Ontario, M5T 2S8, Canada Recruiting Behnaz Ghazanfari, MD, CCRP 416-603-5800 5910 [email protected] Maria Carmela Tartaglia, MD, FRCPC Principal Investigator
Location Countries

Canada

United States

Verification Date

July 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Arm Group

Label: Patients with FTLD or family members

Description: Participants with FTLD syndrome diagnoses and/or strong family histories of FTLD.

Acronym ARTFL
Study Design Info

Observational Model: Cohort

Time Perspective: Prospective

Source: ClinicalTrials.gov