Clinical trial NCT02640092: Longitudinal Evaluation of [18F]GTP1 as a PET Radioligand for Imaging Tau in the Brain of Participants With Alzheimer's Disease Compared to Healthy Participants
Official title: Longitudinal Evaluation of [18F]GTP1 as a PET Radioligand for Imaging Tau in the Brain of Patients With Prodromal, Mild, and Moderate Alzheimer's Disease Compared to Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-12-28
Enrollment: 72
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This is an open-label, longitudinal observational study evaluating the imaging characteristics of the tau positron-emission tomography (PET) radioligand \[18F\] Genentech Tau Probe 1 (GTP1) in the brain of participants with prodromal, mild, and moderate Alzheimer's disease (AD) compared to healthy participants. The overall goal of this protocol is to evaluate the longitudinal change in tau burden using \[18F\]GTP1, a tau targeted radiopharmaceutical.


Eligibility criteria: Inclusion Criteria:

For All Participants:

- Availability of a study partner who, in the investigator's judgment, has frequent and sufficient contact with the participant and is able to provide accurate information regarding the participant's cognitive and functional abilities, agrees to accompany the participant and provide information at visits

For Healthy Participants:

* Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the Baseline \[18F\]GTP1 imaging visit
* Have no cognitive complaint
* Have a Clinical Dementia Rating Scale (CDR) global score = 0
* Have a Mini-Mental State Examination (MMSE) score of 28-30

For Participants With a Diagnosis of AD:

* Participants with mild or moderate AD must meet National Institute on Aging - Alzheimer's Association (NIA-AA) core clinical criteria for probable AD dementia, with an amnestic presentation
* Participants with prodromal AD must meet NIA-AA core clinical criteria for mild cognitive impairment (MCI)
* Have screening \[18F\]florbetapir PET imaging demonstrating amyloid binding based on qualitative visual read
* A brain MRI consistent with a diagnosis of AD, with no evidence of non-AD disease to account for dementia or MRI exclusion criteria
* Medications taken for symptomatic treatment of AD must remain stable for at least 30 days prior to screening visit
* Satisfy one of the following subgroups: Approximately 20 prodromal AD (MMSE 24-30, CDR = 0.5); Approximately 20 mild AD (MMSE 22-30, CDR = 0.5 or 1); Approximately 20 moderate AD (MMSE 16-21, CDR = 0.5 or 1 or 2)

Exclusion Criteria:

* Current or prior history of any drug or alcohol abuse
* Participants with any significant psychiatric, neurological, or unstable medical disorder expected to interfere with the study
* Participants unable to undergo MRI and PET scan
* For participants contributing CSF samples, any contraindication to lumbar puncture
* Prior participation in other research protocols or clinical care in the last year such a radiation exposure combined with that from the present study exceeds an effective dose of 50 millisievert (mSV), the allowable annual limit for research participants as stipulated by the Food and Drug Administration (FDA)

Primary outcomes:
measure: Change in Standardized Uptake Value Ratio (SUVR) as Measured by [18F]GTP1
timeFrame: From Baseline to 18 months
Secondary outcomes:
measure: Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)13
timeFrame: From Baseline to 18 months
measure: Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Volumetric Magnetic Resonance Imaging (MRI) Measures
timeFrame: From Baseline to 18 months
measure: Correlation Coefficient Between Change in SUVR (as Measured by [18F]GTP1) and Change in Cerebrospinal Fluid (CSF) Markers
timeFrame: From Baseline to 18 months
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: From Baseline to 18 months
measure: Test-Retest Variability Based on [18F]GTP1 PET Scans
timeFrame: From date of test scan to 7-21 days after test scan
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Molecular NeuroImaging
state: Connecticut
city: Stamford
country: United States
facility: KI Health Partners, LLC; New England Institute for Clinical Research
state: Connecticut
city: Fort Myers
country: United States
facility: Neuropsychiatric Research; Center of Southwest Florida
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health Systems
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Decatur
country: United States
facility: NeuroStudies.net, LLC
state: Georgia
city: Bangor
country: United States
facility: Acadia Clinical Research; Dr. Henderson's Office
state: Maine
city: Plymouth
country: United States
facility: Donald S. Marks, M.D., P.C.; Medical Center
state: Massachusetts
city: Quincy
country: United States
facility: Alzheimers Disease Center
state: Massachusetts
city: Mount Arlington
country: United States
facility: NeuroCognitive Institute
state: New Jersey
city: Toms River
country: United States
facility: Bio Behavioral Health
state: New Jersey
city: Maumee
country: United States
facility: Advanced Medical Research
state: Ohio
city: Allentown
country: United States
facility: Lehigh Center Clinical Research
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Mood & Memory Research Institute
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Teng E, Manser PT, Sanabria Bohorquez S, Wildsmith KR, Pickthorn K, Baker SL, Ward M, Kerchner GA, Weimer RM. Baseline [18F]GTP1 tau PET imaging is associated with subsequent cognitive decline in Alzheimer's disease. Alzheimers Res Ther. 2021 Dec 1;13(1):196. doi: 10.1186/s13195-021-00937-x.
citation: Blennow K, Chen C, Cicognola C, Wildsmith KR, Manser PT, Bohorquez SMS, Zhang Z, Xie B, Peng J, Hansson O, Kvartsberg H, Portelius E, Zetterberg H, Lashley T, Brinkmalm G, Kerchner GA, Weimer RM, Ye K, Hoglund K. Cerebrospinal fluid tau fragment correlates with tau PET: a candidate biomarker for tangle pathology. Brain. 2020 Feb 1;143(2):650-660. doi: 10.1093/brain/awz346.