Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

Amyotrophic Lateral Sclerosis (ALS) Clinical Trial

— ARTFL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02365922
• Other study ID #: ARTFL8101
• Secondary ID: 1U54NS092089-01
• Status: Completed
• Start date: September 2014
• Est. completion date: September 2020

Study information

• Verified date: May 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1489
• Est. completion date: September 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Amyotrophic Lateral Sclerosis (ALS)
• Aphasia
• Aphasia, Primary Progressive
• Behavioral Variant Frontotemporal Dementia (bvFTD)
• Corticobasal Degeneration (CBD)
• Corticobasal Syndrome (CBS)
• Dementia
• Frontotemporal Dementia
• Frontotemporal Dementia (FTD)
• Frontotemporal Lobar Degeneration
• FTD With Amyotrophic Lateral Sclerosis (FTD/ALS)
• FTLD
• Motor Neuron Disease
• Nonfluent Variant Primary Progressive Aphasia (nfvPPA)
• Oligosymptomatic PSP (oPSP)
• Pick Disease of the Brain
• PPA Syndrome
• Progressive Supranuclear Palsy (PSP)
• Sclerosis
• Semantic Variant Primary Progressive Aphasia (svPPA)
• Supranuclear Palsy, Progressive
• Syndrome

Locations

Country	Name	City	State
Canada	University of Toronto	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Alabama	Birmingham	Alabama
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Harvard University Massachusetts General Hospital	Charlestown	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	Case Western Reserve University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	University of California, Los Angeles	Los Angeles	California
United States	Columbia University	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	University of California, San Diego	San Diego	California
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington Harborview Medical Center	Seattle	Washington

Sponsors (5)

Lead Sponsor	Collaborator
University of California, San Francisco	National Center for Advancing Translational Science (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), Tau Consortium, The Bluefield Project to Cure Frontotemporal Dementia

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (8)

Boeve BF. Progressive supranuclear palsy. Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S192-4. doi: 10.1016/S1353-8020(11)70060-8. Review. — View Citation

Boeve BF. The multiple phenotypes of corticobasal syndrome and corticobasal degeneration: implications for further study. J Mol Neurosci. 2011 Nov;45(3):350-3. doi: 10.1007/s12031-011-9624-1. Epub 2011 Aug 19. Review. — View Citation

Boxer AL, Garbutt S, Seeley WW, Jafari A, Heuer HW, Mirsky J, Hellmuth J, Trojanowski JQ, Huang E, DeArmond S, Neuhaus J, Miller BL. Saccade abnormalities in autopsy-confirmed frontotemporal lobar degeneration and Alzheimer disease. Arch Neurol. 2012 Apr;69(4):509-17. doi: 10.1001/archneurol.2011.1021. — View Citation

Boxer AL, Knopman DS, Kaufer DI, Grossman M, Onyike C, Graf-Radford N, Mendez M, Kerwin D, Lerner A, Wu CK, Koestler M, Shapira J, Sullivan K, Klepac K, Lipowski K, Ullah J, Fields S, Kramer JH, Merrilees J, Neuhaus J, Mesulam MM, Miller BL. Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2013 Feb;12(2):149-56. doi: 10.1016/S1474-4422(12)70320-4. Epub 2013 Jan 2. — View Citation

Boxer AL, Lang AE, Grossman M, Knopman DS, Miller BL, Schneider LS, Doody RS, Lees A, Golbe LI, Williams DR, Corvol JC, Ludolph A, Burn D, Lorenzl S, Litvan I, Roberson ED, Höglinger GU, Koestler M, Jack CR Jr, Van Deerlin V, Randolph C, Lobach IV, Heuer HW, Gozes I, Parker L, Whitaker S, Hirman J, Stewart AJ, Gold M, Morimoto BH; AL-108-231 Investigators. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014 Jul;13(7):676-85. doi: 10.1016/S1474-4422(14)70088-2. Epub 2014 May 27. — View Citation

Rohrer JD, Rosen HJ. Neuroimaging in frontotemporal dementia. Int Rev Psychiatry. 2013 Apr;25(2):221-9. doi: 10.3109/09540261.2013.778822. Review. — View Citation

Rosen HJ, Alcantar O, Rothlind J, Sturm V, Kramer JH, Weiner M, Miller BL. Neuroanatomical correlates of cognitive self-appraisal in neurodegenerative disease. Neuroimage. 2010 Feb 15;49(4):3358-64. doi: 10.1016/j.neuroimage.2009.11.041. Epub 2009 Dec 1. — View Citation

Rosen HJ, Alcantar O, Zakrzewski J, Shimamura AP, Neuhaus J, Miller BL. Metacognition in the behavioral variant of frontotemporal dementia and Alzheimer's disease. Neuropsychology. 2014 May;28(3):436-47. doi: 10.1037/neu0000012. Epub 2014 Feb 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Scores of UDS FTLD Module Tests	Neuropsychological test scores from the Uniform Data Set FTLD Module will be collected and compared across patient populations.	Baseline, 12 mo.
Secondary	Progressive Supranuclear Palsy Rating Scale (PSPRS)	Scores will be compared among patient populations	Baseline
Secondary	Neuroimaging	In asymptomatic family members of FTLD patients, changes from baseline neuroimaging will be assessed 12 months later.	Baseline; 12 months