Assessment of Hyperphosphorylated Tau PET Binding in Primary Progressive Aphasia and Frontotemporal Dementia (SLD3)

Mayo Clinic

Status and phase: Completed; Phase 1

Conditions: Primary Progressive Aphasia; Frontotemporal Dementia, Behavioral Variant; Behavioral Variant of Frontotemporal Dementia

Treatments: Drug: F-18 AV 1451

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02736695

1R21NS094684-01 (U.S. NIH Grant/Contract)

16-001703

Details and patient eligibility

About

This study is designed to learn more about overall tau burden in the brain of patients with Primary Progressive Aphasia (PPA) and Frontotemporal Dementia.

Full description

Primary progressive aphasia (PPA) is an umbrella term that encompasses a group of neurodegenerative syndromes characterized by varying combinations of progressive speech and language problems. Three clinical variants of PPA have been described and are well recognized: the agrammatic variant characterized by grammatical errors in speech and writing and typically associated with phonetic errors in speech; the semantic variant characterized by poor naming from loss of knowledge about the meaning of words; and the logopenic variant characterized by word retrieval problems and poor sentence repetition from impairment of working memory and phonemic errors. Pathological studies of PPA patients that died with postmortem examination of their brains have demonstrated that PPA is associated with a number of different abnormal cellular proteins that do not have perfect associations with the three PPA variants. One such protein is the microtubule associated protein, tau, which is the most common abnormal protein found in the brains of patients with PPA. Tau is an important protein that has been linked to the neurodegenerative process in many diseases. No neuroimaging studies have investigated tau deposition in PPA and hence the binding characteristics of AV-1451 (the Tau binding drug used in this study) in PPA are unknown. Understanding the binding characteristics of AV-1451 is crucial to help determine whether it can serve as a biomarker for tau deposition in the brains of patients with PPA.

FTD or Frontotemporal Dementias, including bvFTD, will also be included in this study.

Enrollment: 81 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Must be over the age of 18
• Must speak English as your primary language
• Must have an informant who can provide independent evaluation of functioning
• Must present with a chief complaint of progressive impairment of speech/language or changes in behavior
• Must fulfill diagnostic criteria for Primary Progressive Aphasia or Frontotemporal Dementia

Exclusion criteria

• Any subject who is mute or whose speech is unintelligible will be excluded
• All subjects with concurrent illnesses that could account for speech and language deficits, such as traumatic brain injury, strokes or developmental syndromes, and subjects meeting criteria for another neurodegenerative disease, such as amnestic Alzheimer's type dementia, dementia with Lewy bodies, progressive supranuclear palsy, and corticobasal syndrome will be excluded
• All pregnant, post-partum and breast-feeding women will be excluded
• Subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, etc.), if there is severe claustrophobia, if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm), or if they are medically unstable or are on medications that might affect brain structure or metabolism,(e.g. chemotherapy).
• Subjects who meet criteria for PPA and have mild behavioral changes, eye movement abnormalities or mild limb apraxia but who do not meet diagnostic criteria for, progressive supranuclear palsy or corticobasal syndrome respectively, will also be excluded.
• Subjects will be excluded from the study if they have any of the following genetic conditions which can increase the chance of cancer: Cowden disease, Lynch syndrome, hypogammaglobulinemia, Wiskott-Aldrich syndrome, and Down's syndrome.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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81 participants in 2 patient groups

Tau PET Scan, F-18 AV 1451

Experimental group

Description:

All subjects will receive a Tau PET scan.

Treatment:

Drug: F-18 AV 1451

Normal Controls

No Intervention group

Description:

Subjects from our NIH funded Mayo Clinic Study of Aging (U01 AG006786) who have completed the identical tau-PET protocol with AV-1451 and MRI and clinical protocols. These participants were not consented or enrolled in this study.