AZD0530 is an inhibitor of Src and Abl family kinases1. It has been developed as treatment for malignancies because these kinases play a role in tumor invasion and proliferation. However, the Src family kinases (SFKs) are highly expressed in brain and have major effects on synaptic plasticity2. Moreover, the investigators have recently shown that a specific SFK, namely Fyn, is aberrantly activated by specific conformations of the Amyloid Beta (Aß) peptide from Alzheimer's disease (AD). Genetic deletion of Fyn rescues AD deficits in preclinical models. This clinical trial will test the potential benefit of AZD0530 for Alzheimer's disease modification.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
159
All patients in experimental group (50%) will be started on 100mg AZD0530 daily
Patients with plasma drug level \<100ng/ml after 2 weeks of 100mg AZD0530 daily will receive 125mg daily of AZD0530.
50% of patients will receive placebo treatment for the duration of the study.
Barrow Neurological Institute
Phoenix, Arizona, United States
Banner Sun Health Research Institute
Sun City, Arizona, United States
University of California, Los Angeles
Los Angeles, California, United States
Yale Alzheimer's Disease Research Unit
New Haven, Connecticut, United States
Georgetown University
Washington D.C., District of Columbia, United States
Wien Center for Clinical Research/Mount Sinai Medical Center
Miami Beach, Florida, United States
University of South Florida - Health Byrd Alzheimer Institute
Tampa, Florida, United States
Northwestern University
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
Indiana University
Indianapolis, Indiana, United States
...and 12 more locations
Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging
Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.
Time frame: 12 months
Number of Participants With One or More Serious/Other Adverse Events Subjects With Mild AD as Assessed by Analysis of Adverse Events, Including Symptoms, and Abnormal Findings on Physical and Neurological Examinations, and Standard Labs.
Assessment of any adverse effects between drug and placebo-treated subjects
Time frame: 12 months
The Effect of Treatment With AZD0530 on Cognitive and Behavioral Function
The change in cognitive function between baseline and 12 months will be measured by the following tests: 1. Alzheimer Disease Assessment Scale - Cognitive 11 (ADAS-cog11). Measures: Cognitive function Maximum score: 70; Minimum score: 0. Higher score equals worse cognitive function 2. Mini-Mental State Examination (MMSE) Measures: Cognitive Function Maximum score: 30; Minimum score: 0. Higher score equal better cognitive function 3. Alzheimer Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL) Measures: Ability to perform routine daily activities Maximum score: 78; Minimum score: 0. Higher score equals better ability to perform activities of daily living 4. Clinical Dementia Rating Sum of Boxes (CDR-SO) Measures: Dementia severity Maximum score: 18; Minimum score: 0. Higher score equals more severe dementia.
Time frame: 12 months
Percent Change in Brain Volume Before and After Treatment
Change in volume of pre-defined brain regions between baseline and 12 months of treatment.
Time frame: 12 months
Cerebrospinal Fluid Levels of Total Tau, Phospho-tau (p-Tau), and Amyloid-beta 1-42 (Abeta 1-42)
Measure concentration of Tau and Amyloid-beta 1-42 biomarkers in the cerebrospinal fluid between baseline and 12 months of treatment
Time frame: 12 months
Change in Brain Glucose Uptake Measured Using 18F-FDG PET Imaging
The results from the primary outcome with brain FDG-PET imaging was analyzed by ApoE genotype. Composite measure of brain glucose uptake using F18-FDG PET in a pre-defined set of brain regions, between baseline and 12 months.
Time frame: 12 months
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